Discovery of Peptidic Siderophore Degradation by Screening Natural Product Profiles in Marine-Derived Bacterial Mono- and CoculturesClick to copy article linkArticle link copied!
- Mónica Monge-LoríaMónica Monge-LoríaSchool of Chemistry and Biochemistry, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, Georgia 30332, United StatesMore by Mónica Monge-Loría
- Weimao ZhongWeimao ZhongSchool of Chemistry and Biochemistry, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, Georgia 30332, United StatesMore by Weimao Zhong
- Nadine H. AbrahamseNadine H. AbrahamseSchool of Chemistry and Biochemistry, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, Georgia 30332, United StatesMore by Nadine H. Abrahamse
- Stephen HartterStephen HartterGeorgia Aquarium, 225 Baker St. NW, Atlanta, Georgia 30313, United StatesMore by Stephen Hartter
- Neha Garg*Neha Garg*Email: [email protected]School of Chemistry and Biochemistry, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, Georgia 30332, United StatesCenter for Microbial Dynamics and Infection, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, Georgia 30332, United StatesMore by Neha Garg
Abstract
Coral reefs are hotspots of marine biodiversity, which results in the synthesis of a wide variety of compounds with unique molecular scaffolds, and bioactivities, rendering reefs an ecosystem of interest. The chemodiversity stems from the intricate relationships between inhabitants of the reef, as the chemistry produced partakes in intra- and interspecies communication, settlement, nutrient acquisition, and defense. However, the coral reefs are declining at an unprecedented rate due to climate change, pollution, and increased incidence of pathogenic diseases. Among pathogens, Vibrio spp. bacteria are key players resulting in high mortality. Thus, alternative strategies such as application of beneficial bacteria isolated from disease-resilient species are being explored to lower the burden of pathogenic species. Here, we apply coculturing of a coral-derived pathogenic species of Vibrio and beneficial bacteria and leverage recent advancements in untargeted metabolomics to discover engineerable beneficial traits. By chasing chemical change in coculture, we report Microbulbifer spp.-mediated degradation of amphibactins, produced by Vibrio spp. bacteria to sequester iron. Additional biochemical experiments revealed that the degradation occurs in the peptide backbone and requires the enzyme fraction of Microbulbifer. A reduction in iron affinity is expected due to the loss of one Fe(III) binding moiety. Therefore, we hypothesize that this degradation shapes community behaviors as it pertains to iron acquisition, a limiting nutrient in the marine environment, and survival. Furthermore, Vibrio sp. bacteria suppressed natural product synthesis by beneficial bacteria. Understanding biochemical mechanisms behind these interactions will enable engineering probiotic bacteria capable of lowering pathogenic burdens during heat waves and incidence of disease.
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License Summary*
You are free to share(copy and redistribute) this article in any medium or format and to adapt(remix, transform, and build upon) the material for any purpose, even commercially within the parameters below:
Creative Commons (CC): This is a Creative Commons license.
Attribution (BY): Credit must be given to the creator.
*Disclaimer
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License Summary*
You are free to share(copy and redistribute) this article in any medium or format and to adapt(remix, transform, and build upon) the material for any purpose, even commercially within the parameters below:
Creative Commons (CC): This is a Creative Commons license.
Attribution (BY): Credit must be given to the creator.
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Special Issue
Published as part of Biochemistry special issue “A Tribute to Christopher T. Walsh”.
Introduction
Results and Discussion
Comparative Metabolomics of Bacterial Mono- and Cocultures with V. coralliilyticus Cn52-H1
Figure 1
Figure 1. Bacterial isolation and metabolomics workflow. (A) Bacterial isolation from coral mucus, tissue, and the remaining skeleton was performed on six different culture media. Morphologically distinct colonies were isolated and restreaked to ensure purity. (B) Prioritized isolates’ phenotype in mono- and coculture with V. coralliilyticus Cn52-H1. (C) Prioritized strains were cocultured with V. coralliilyticus Cn52-H1, metabolites were extracted using liquid–liquid extraction (LLE), solid phase extraction (SPE), and solid–liquid extraction (SLE). The extracts were analyzed using UPLC-MS and the data was processed for downstream analysis using a suite of cheminformatics tools for compound annotation.
strain | genus | origin | references |
---|---|---|---|
Cnat2–18.1 | Pseudoalteromonas | Coral; Colpophyllia natans, Atlantic Ocean | (23) |
DL2H-2.2 | Pseudoalteromonas | Coral; Diploria labyrinthiformis, Atlantic Ocean | (23) |
Ofav2–7 | Photobacterium | Coral; Orbicella faveolata, Atlantic Ocean | (23) |
AC-K1-M-019 | Pseudoalteromonas | Coral; A. cervicornis, Georgia Aquarium | this work |
CNSA002 | Microbulbifer | Sponge; Smenospongia aurea, Atlantic Ocean | (66) |
VASA001 | Bacillus | Sponge; S. aurea, Atlantic Ocean | (66) |
Figure 2
Figure 2. Metabolome profiling of bacterial mono- and cocultures. (A) FBMN showcasing a subset of features that were annotated in this study and their representative chemical structures. The amphibactin cluster and a cluster of unknown metabolites detected in coculture with Microbulbifer sp. CNSA0002 and sharing the MS2LDA motif 531 with the amphibactin cluster are highlighted with a green circle. (B) A Venn diagram representation of the number of features detected across different culture conditions. (C) An UpSet plot is used to show the distribution of 76 features unique to cocultures. (D) PCA plot of untargeted metabolomics data acquired on extracts of V. coralliilyticus Cn52-H1 monoculture, Microbulbifer sp. CNSA002 monoculture and their coculture.
Annotation of Features Variably Detected in CNSA002 Coculture
Figure 3
Figure 3. Amphibactin degradation by Microbulbifer sp. CNSA002. (A) MS2LDA motif 531, annotated as containing N-acetyl-N-hydroxy-ornithine. (B) Spectral comparison of amphibactin F and unknown feature with m/z 617.411 produced only in coculture. (C) MS2 mirror plot of amphibactin F and Fe(III)-amphibactin F. No Fe(III)-bound complex of m/z 617.411 was observed. (D) Amphibactin F, produced by V. coralliilyticus Cn52-H1 is degraded in the presence of Microbulbifer sp. CNSA002 cell-free supernatant producing compound 1, structurally elucidated through NMR (Table S4 and Figures S4–S12). Iron-binding hydroxamate moieties are circled. (E) Boxplots of the relative abundances of amphibactin F and its degradation product in their apo- and complex form in monoculture and coculture. (F) Petri plate showing iron chelating activity of purified compound 1 using O-CAS agar assay.
Figure 4
Figure 4. Detection of amphibactins and their degradation products. (A) Boxplots of the relative abundances of amphibactin F (876.529 m/z) and its degradation product (617.412 m/z) in monoculture of V. coralliilyticus Cn52-H1, Microbulbifer sp. CNSA002, their coculture, and Cn52-H1 culture in the presence of cell-free supernatant of CNSA002. (B) Boxplots of relative abundances of degraded amphibactin F in V. coralliilyticus Cn52-H1 cell-free supernatant alone, after boiling, and in the presence of flow through or retentate of an ultrafiltration experiment with either a 3 kDa or 10 kDa membrane. (C) Boxplots of amphibactins and (D) their degradation products in V. coralliilyticus Cn52-H1 monoculture and its coculture with Microbulbifer sp. CNSA002. (E) New amphibactin analogs indirectly identified through their degradation products in Microbulbifer sp. CNSA002 and V. coralliilyticus Cn52-H1 cocultures. The position of double bond was not determined and is putatively placed (shown with dashed line). (F) Boxplots of the relative abundances of amphibactin F and its degradation product in V. coralliilyticus Cn52-H1 monoculture and in coculture with several Microbulbifer sp. strains.
Figure 5
Figure 5. Detection of hydroxamate siderophores and ferrisiderophores in the presence of Microbulbifer sp. CNSA002. (A) Boxplot of the relative abundances of desferrioxamine E and ferrioxamine E (601.356 m/z and 654.267 m/z respectively) in Pseudoalteromonas sp. Cnat2–18.1 and Microbulbifer sp. CNSA002 mono- and coculture. (B) Boxplot of the relative abundances of desferrichrome and ferrichrome (688.326 m/z and 741.237 m/z respectively) when supplemented in a Microbulbifer sp. CNSA002 culture and controls. (C) Representative structures of peptidic hydroxamate siderophores: aquachelin, marinobactin, and moanachelin.
name | theoretical m/z [M + H]+ | experimental m/z [M + H]+ | error (ppm) | corresponding amphibactin | theoretical m/z [M + H]+ | acyl tail | references |
---|---|---|---|---|---|---|---|
degraded amphibactin D | 573.386 | 573.386 | 0 | Amphibactin D | 832.5026 | C14:0 | (78) |
degraded amphibactin V | 587.401 | 587.401 | 0 | Amphibactin V | 846.5183 | C15:0 | (79) |
degraded amphibactin B | 589.381 | 589.381 | 0 | Amphibactin B | 848.4975 | C14:0;3-OH | (78) |
degraded amphibactin E | 599.401 | 599.402 | 1.7 | Amphibactin E | 858.5183 | C16:1 | (78) |
degraded amphibactin H | 601.417 | 601.417 | 0 | Amphibactin H | 860.5339 | C16:0 | (78) |
degraded amphibactin C | 615.396 | 615.397 | 1.6 | Amphibactin C | 874.5132 | C16:1;3-OH | (78) |
degraded amphibactin F | 617.412 | 617.412 | 0 | Amphibactin F | 876.5288 | C16:0;3-OH | (78) |
degraded amphibactin I | 627.433 | 627.433 | 0 | Amphibactin I | 886.5496 | C18:1 | (78) |
degraded amphibactin G | 643.428 | 643.427 | 1.6 | Amphibactin G | 902.5445 | C18:1;3-OH | (78) |
degraded amphibactin analog 1 | 575.365 | 575.365 | 0 | Analog 1 | 834.4819 | C13:0;3-OH | this work |
degraded amphibactin analog 2 | 587.365 | 587.366 | 1.7 | Analog 2 | 846.4819 | C14:1a;3-OH | this work |
degraded amphibactin analog 3 | 597.386 | 597.386 | 0 | Analog 3 | 856.5026 | C16:2a | this work |
degraded amphibactin analog 4 | 603.396 | 603.397 | 1.7 | Analog 4 | 862.5132 | C15:0;3-OH | this work |
degraded amphibactin analog 5 | 629.412 | 629.412 | 0 | Analog 5 | 888.5284 | C17:1a;3-OH | this work |
degraded amphibactin analog 6 | 631.428 | 631.427 | 1.6 | Analog 6 | 890.5437 | C17:0;3-OH | this work |
degraded amphibactin analog 7 | 645.443 | 645.443 | 0 | Analog 7 | 904.5599 | C18:0;3-OH | this work |
Position of double bond was not determined.
Enzymatic Degradation of Amphibactins and New Amphibactin Analogs
Specificity of Siderophore Degradation
Annotation and Variable Detection of Additional Natural Products
Figure 6
Figure 6. Boxplots of the relative abundances of bulbiferamide A, prodigiosin and bromotryptamine as well as a representative panel of N-acyl amides, in monoculture and coculture conditions. Asterisks indicate significant differences between the compared groups.
Conclusions
Methods
Bacterial Isolation
Bacterial Coculturing
Untargeted Metabolomics Data Acquisition and Analysis
Fermentation, Extraction, and Compound Purification
O-CAS Agar Assay
CNSA002 Whole Genome Sequencing
Enzymatic Hydrolysis of Amphibactin
Ferrichrome and Desferrioxamine Degradation Assays
Data Availability
Mirobulbifer sp. CNSA002 whole genome sequence has been deposited in NCBI under the bioproject PRJNA1173768. NMR data for compound 1 has been deposited to NP-MRD (173) (ID: NP0341873). LCMS data has been deposited in GNPS-MassIVE and the data set ID is MSV000096127.
Supporting Information
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.biochem.4c00706.
Representative feature-based molecular networking for mono- and coculture experiments (Figure S1); Heatmap of the top 50 features in monocultures and coculture of V. coralliilyticus Cn52-H1 and Microbulbifer sp. CNSA002 (Figure S2); natural product extraction and characterization workflow (Figure S3); amphibactin F degradation product, elucidated through 1D and 2D NMR experiments (Figure S4); NMR data for compound 1 (Figures S5–S12); MS2 spectral analysis of amphibactins and new amphibactin analogs (Figures S13 and S14); Microbulbifer sp. CNSA002 O-CAS agar assay (Figure S15); detection of degraded amphibactins in V. coralliilyticus Cn52-H1 in coculture with Microbulbifer sp. CNSA002 and supplemented with Microbulbifer sp. CNSA002 supernatant and CNSA002 fractions (Figures S16 and17); Boxplot of the relative abundances of desferrioxamine G and ferrioxamine G in Pseudoalteromonas sp. Cnat2–18.1 and Microbulbifer sp. CNSA002 monocultures and coculture (Figure S18); mirror plots comparing experimental MS2 spectra of natural products, hydroxamate siderophores and N-acyl amides detected in this study with spectra deposited in the GNPS library (Figures S19–21); upset plot for N-acyl amides detected in different monocultures and cocultures (Figure S22); putative annotation of top 50 features present in the V. coralliilyticus Cn52-H1 and Microbulbifer sp. CNSA002 coculture heatmap (Table S1); putative annotation of 76 features uniquely detected in marine bacteria cocultures with V. coralliilyticus Cn52-H1 (Table S2); list of annotated metabolites detected in this study (Table S3); 1H (700 MHz) and 13C (176 MHz) NMR data of compound 1 in DMSO-d6 (Table S4); biosynthetic gene clusters present in Microbulbifer sp. bacteria analyzed in this study (Table S5); list of annotated N-acyl amides detected in this study (Table S6) (PDF)
Terms & Conditions
Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.
Acknowledgments
This work was supported by the NIH R35GM150870 to N.G. We thank Dr. Valerie Paul at the Smithsonian Marine Station, Dr. Vinayak Agarwal, Georgia Institute of Technology and Dr. Blake Ushijima, UNCW for sharing their bacterial strains with us. We thank Dr. Vinayak Agarwal for his support in NMR data acquisition and compound isolation. We thank Dr. Alistair Dove and the entire research team of Georgia Aquarium for giving us the opportunity to work with them.
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- 28Ritchie, K. B. Regulation of Microbial Populations by Coral Surface Mucus and Mucus-Associated Bacteria. Mar. Ecol.: Prog. Ser. 2006, 322, 1– 14, DOI: 10.3354/meps322001Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtlCisLfO&md5=f88503af746c42dfe7537d4b162e57e2Regulation of microbial populations by coral surface mucus and mucus-associated bacteriaRitchie, Kim B.Marine Ecology: Progress Series (2006), 322 (), 1-14CODEN: MESEDT; ISSN:0171-8630. (Inter-Research)Caribbean populations of the elkhorn coral Acropora palmata have declined due to environmental stress, bleaching, and disease. Potential sources of coral mortality include invasive microbes that become trapped in the surface mucus and thrive under conditions of increased coral stress. In this study, mucus from healthy A. palmata inhibited growth of potentially invasive microbes by up to 10-fold. Among cultured bacteria from the mucus of A. palmata, 20% displayed antibiotic activity against one or more tester strains, including the pathogen implicated in white pox disease. A novel mucus-mediated selection for coral symbionts revealed a discrete subset of bacteria and selected for isolates that produce antibiotics. This result suggests that coral mucus plays a role in the structuring of beneficial coral-assocd. microbial communities and implies a microbial contribution to the antibacterial activity described for coral mucus. Interestingly, antibiotic activity was lost when mucus was collected during a summer bleaching event. Isolates from apparently healthy A. palmata tissue during this event lacked antibiotic-producing bacteria and were dominated by members of the genus Vibrio, including species implicated in temp.-dependent bleaching of corals worldwide. This indicates an environmental shift from beneficial bacteria, and variability in the protective qualities of coral mucus, which may lead to an overgrowth of opportunistic microbes when temps. increase. Finally, coral mucus inhibited antibiotic activity and pigment prodn. in a potentially invasive bacterium, illustrating that coral mucus may inactivate mechanisms used for bacterial niche establishment.
- 29Raina, J.-B.; Tapiolas, D.; Motti, C. A.; Foret, S.; Seemann, T.; Tebben, J.; Willis, B. L.; Bourne, D. G. Isolation of an antimicrobial compound produced by bacteria associated with reef-building corals. PeerJ 2016, 4, e2275 DOI: 10.7717/peerj.2275Google ScholarThere is no corresponding record for this reference.
- 30Kvennefors, E. C. E.; Sampayo, E.; Kerr, C.; Vieira, G.; Roff, G.; Barnes, A. C. Regulation of Bacterial Communities Through Antimicrobial Activity by the Coral Holobiont. Microb. Ecol. 2012, 63 (3), 605– 618, DOI: 10.1007/s00248-011-9946-0Google ScholarThere is no corresponding record for this reference.
- 31Delgadillo-Ordoñez, N.; Garcias-Bonet, N.; Raimundo, I.; García, F. C.; Villela, H.; Osman, E. O.; Santoro, E. P.; Curdia, J.; Rosado, J. G. D.; Cardoso, P.; Alsaggaf, A.; Barno, A.; Antony, C. P.; Bocanegra, C.; Berumen, M. L.; Voolstra, C. R.; Benzoni, F.; Carvalho, S.; Peixoto, R. S. Probiotics reshape the coral microbiome in situ without detectable off-target effects in the surrounding environment. Commun. Biol. 2024, 7 (1), 434 DOI: 10.1038/s42003-024-06135-3Google ScholarThere is no corresponding record for this reference.
- 32Papke, E.; Carreiro, A.; Dennison, C.; Deutsch, J. M.; Isma, L. M.; Meiling, S. S.; Rossin, A. M.; Baker, A. C.; Brandt, M. E.; Garg, N.; Holstein, D. M.; Traylor-Knowles, N.; Voss, J. D.; Ushijima, B. Stony coral tissue loss disease: a review of emergence, impacts, etiology, diagnostics, and intervention. Front. Mar. Sci. 2024, 10, 1321271 DOI: 10.3389/fmars.2023.1321271Google ScholarThere is no corresponding record for this reference.
- 33Vidal-Dupiol, J.; Ladrière, O.; Meistertzheim, A. L.; Fouré, L.; Adjeroud, M.; Mitta, G. Physiological responses of the scleractinian coral Pocillopora damicornis to bacterial stress from Vibrio coralliilyticus. J. Exp. Biol. 2011, 214 (Pt 9), 1533– 1545, DOI: 10.1242/jeb.053165Google ScholarThere is no corresponding record for this reference.
- 34Roder, C.; Arif, C.; Bayer, T.; Aranda, M.; Daniels, C.; Shibl, A.; Chavanich, S.; Voolstra, C. R. Bacterial profiling of White Plague Disease in a comparative coral species framework. Isme J. 2014, 8 (1), 31– 39, DOI: 10.1038/ismej.2013.127Google ScholarThere is no corresponding record for this reference.
- 35Ben-Haim, Y.; Zicherman-Keren, M.; Rosenberg, E. Temperature-regulated bleaching and lysis of the coral Pocillopora damicornis by the novel pathogen Vibrio coralliilyticus. Appl. Environ. Microbiol. 2003, 69 (7), 4236– 4242, DOI: 10.1128/AEM.69.7.4236-4242.2003Google ScholarThere is no corresponding record for this reference.
- 36Estes, R. M.; Friedman, C. S.; Elston, R. A.; Herwig, R. P. Pathogenicity testing of shellfish hatchery bacterial isolates on Pacific oyster Crassostrea gigas larvae. Dis. Aquat. Org. 2004, 58 (2–3), 223– 230, DOI: 10.3354/dao058223Google ScholarThere is no corresponding record for this reference.
- 37Manchanayake, T.; Salleh, A.; Amal, M. N. A.; Yasin, I. S. M.; Zamri-Saad, M. Pathology and pathogenesis of Vibrio infection in fish: A review. Aquacult. Rep. 2023, 28, 101459 DOI: 10.1016/j.aqrep.2022.101459Google ScholarThere is no corresponding record for this reference.
- 38Vizcaino, M. I.; Johnson, W. R.; Kimes, N. E.; Williams, K.; Torralba, M.; Nelson, K. E.; Smith, G. W.; Weil, E.; Moeller, P. D.; Morris, P. J. Antimicrobial resistance of the coral pathogen Vibrio coralliilyticus and Caribbean sister phylotypes isolated from a diseased octocoral. Microb. Ecol. 2010, 59 (4), 646– 657, DOI: 10.1007/s00248-010-9644-3Google ScholarThere is no corresponding record for this reference.
- 39Ushijima, B.; Meyer, J. L.; Thompson, S.; Pitts, K.; Marusich, M. F.; Tittl, J.; Weatherup, E.; Reu, J.; Wetzell, R.; Aeby, G. S.; Häse, C. C.; Paul, V. J. Disease Diagnostics and Potential Coinfections by Vibrio coralliilyticus During an Ongoing Coral Disease Outbreak in Florida. Front. Microbiol. 2020, 11, 569354 DOI: 10.3389/fmicb.2020.569354Google ScholarThere is no corresponding record for this reference.
- 40Heinz, J. M.; Lu, J.; Huebner, L. K.; Salzberg, S. L.; Sommer, M.; Rosales, S. M. Novel metagenomics analysis of stony coral tissue loss disease bioRxiv: The Preprint Server for Biology 2024 DOI: 10.1101/2024.01.02.573916 .Google ScholarThere is no corresponding record for this reference.
- 41Meyer, J. L.; Castellanos-Gell, J.; Aeby, G. S.; Häse, C. C.; Ushijima, B.; Paul, V. J. Microbial Community Shifts Associated With the Ongoing Stony Coral Tissue Loss Disease Outbreak on the Florida Reef Tract. Front. Microbiol. 2019, 10, 2244 DOI: 10.3389/fmicb.2019.02244Google ScholarThere is no corresponding record for this reference.
- 42Shilling, E. N.; Combs, I. R.; Voss, J. D. Assessing the effectiveness of two intervention methods for stony coral tissue loss disease on Montastraea cavernosa. Sci. Rep. 2021, 11 (1), 8566 DOI: 10.1038/s41598-021-86926-4Google ScholarThere is no corresponding record for this reference.
- 43Studivan, M. S.; Eckert, R. J.; Shilling, E.; Soderberg, N.; Enochs, I. C.; Voss, J. D. Stony coral tissue loss disease intervention with amoxicillin leads to a reversal of disease-modulated gene expression pathways. Mol. Ecol. 2023, 32 (19), 5394– 5413, DOI: 10.1111/mec.17110Google ScholarThere is no corresponding record for this reference.
- 44Rubio-Portillo, E.; Santos, F.; Martínez-García, M.; de Los Ríos, A.; Ascaso, C.; Souza-Egipsy, V.; Ramos-Esplá, A. A.; Anton, J. Structure and temporal dynamics of the bacterial communities associated to microhabitats of the coral Oculina patagonica. Environ. Microbiol. 2016, 18 (12), 4564– 4578, DOI: 10.1111/1462-2920.13548Google ScholarThere is no corresponding record for this reference.
- 45Sunagawa, S.; Coelho, L. P.; Chaffron, S.; Kultima, J. R.; Labadie, K.; Salazar, G.; Djahanschiri, B.; Zeller, G.; Mende, D. R.; Alberti, A.; Cornejo-Castillo, F. M.; Costea, P. I.; Cruaud, C.; d’Ovidio, F.; Engelen, S.; Ferrera, I.; Gasol, J. M.; Guidi, L.; Hildebrand, F.; Kokoszka, F.; Lepoivre, C.; Lima-Mendez, G.; Poulain, J.; Poulos, B. T.; Royo-Llonch, M.; Sarmento, H.; Vieira-Silva, S.; Dimier, C.; Picheral, M.; Searson, S.; Kandels-Lewis, S.; Oceans, T.; Bowler, C.; de Vargas, C.; Gorsky, G.; Grimsley, N.; Hingamp, P.; Iudicone, D.; Jaillon, O.; Not, F.; Ogata, H.; Pesant, S.; Speich, S.; Stemmann, L.; Sullivan, M. B.; Weissenbach, J.; Wincker, P.; Karsenti, E.; Raes, J.; Acinas, S. G.; Bork, P.; Boss, E.; Bowler, C.; Follows, M.; Karp-Boss, L.; Krzic, U.; Reynaud, E. G.; Sardet, C.; Sieracki, M.; Velayoudon, D. Structure and function of the global ocean microbiome. Science 2015, 348 (6237), 1261359 DOI: 10.1126/science.1261359Google Scholar45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MfmsVKgtQ%253D%253D&md5=55c0d91e78a4772180b6d5bd6f1769d9Ocean plankton. Structure and function of the global ocean microbiomeSunagawa Shinichi; Coelho Luis Pedro; Kultima Jens Roat; Djahanschiri Bardya; Zeller Georg; Mende Daniel R; Costea Paul I; Hildebrand Falk; Chaffron Samuel; Lima-Mendez Gipsi; Vieira-Silva Sara; Raes Jeroen; Labadie Karine; Alberti Adriana; Cruaud Corinne; Engelen Stefan; Poulain Julie; Salazar Guillem; Cornejo-Castillo Francisco M; Ferrera Isabel; Gasol Josep M; Royo-Llonch Marta; Acinas Silvia G; d'Ovidio Francesco; Guidi Lionel; Picheral Marc; Searson Sarah; Gorsky Gabriel; Stemmann Lars; Kokoszka Florian; Lepoivre Cyrille; Hingamp Pascal; Poulos Bonnie T; Sullivan Matthew B; Sarmento Hugo; Dimier Celine; Kandels-Lewis Stefanie; Bowler Chris; de Vargas Colomban; Not Fabrice; Grimsley Nigel; Iudicone Daniele; Jaillon Olivier; Weissenbach Jean; Wincker Patrick; Ogata Hiroyuki; Pesant Stephane; Speich Sabrina; Karsenti Eric; Bork PeerScience (New York, N.Y.) (2015), 348 (6237), 1261359 ISSN:.Microbes are dominant drivers of biogeochemical processes, yet drawing a global picture of functional diversity, microbial community structure, and their ecological determinants remains a grand challenge. We analyzed 7.2 terabases of metagenomic data from 243 Tara Oceans samples from 68 locations in epipelagic and mesopelagic waters across the globe to generate an ocean microbial reference gene catalog with >40 million nonredundant, mostly novel sequences from viruses, prokaryotes, and picoeukaryotes. Using 139 prokaryote-enriched samples, containing >35,000 species, we show vertical stratification with epipelagic community composition mostly driven by temperature rather than other environmental factors or geography. We identify ocean microbial core functionality and reveal that >73% of its abundance is shared with the human gut microbiome despite the physicochemical differences between these two ecosystems.
- 46Su, H.; Xiao, Z.; Yu, K.; Huang, Q.; Wang, G.; Wang, Y.; Liang, J.; Huang, W.; Huang, X.; Wei, F.; Chen, B. Diversity of cultivable protease-producing bacteria and their extracellular proteases associated to scleractinian corals. PeerJ 2020, 8, e9055 DOI: 10.7717/peerj.9055Google ScholarThere is no corresponding record for this reference.
- 47Wei, Y.; Bu, J.; Long, H.; Zhang, X.; Cai, X.; Huang, A.; Ren, W.; Xie, Z. Community Structure of Protease-Producing Bacteria Cultivated From Aquaculture Systems: Potential Impact of a Tropical Environment. Front. Microbiol. 2021, 12, 638129 DOI: 10.3389/fmicb.2021.638129Google ScholarThere is no corresponding record for this reference.
- 48Zhou, M.-Y.; Wang, G.-L.; Li, D.; Zhao, D.-L.; Qin, Q.-L.; Chen, X.-L.; Chen, B.; Zhou, B.-C.; Zhang, X.-Y.; Zhang, Y.-Z. Diversity of Both the Cultivable Protease-Producing Bacteria and Bacterial Extracellular Proteases in the Coastal Sediments of King George Island, Antarctica. PLoS One 2013, 8 (11), e79668 DOI: 10.1371/journal.pone.0079668Google ScholarThere is no corresponding record for this reference.
- 49Cristóbal, H. A.; López, M. A.; Kothe, E.; Abate, C. M. Diversity of protease-producing marine bacteria from sub-antarctic environments. J. Basic Microbiol. 2011, 51 (6), 590– 600, DOI: 10.1002/jobm.201000413Google ScholarThere is no corresponding record for this reference.
- 50Zhang, J.; Chen, M.; Huang, J.; Guo, X.; Zhang, Y.; Liu, D.; Wu, R.; He, H.; Wang, J. Diversity of the microbial community and cultivable protease-producing bacteria in the sediments of the Bohai Sea, Yellow Sea and South China Sea. PLoS One 2019, 14 (4), e0215328 DOI: 10.1371/journal.pone.0215328Google ScholarThere is no corresponding record for this reference.
- 51Paulsen, S. S.; Strube, M. L.; Bech, P. K.; Gram, L.; Sonnenschein, E. C. Marine Chitinolytic Pseudoalteromonas Represents an Untapped Reservoir of Bioactive Potential. mSystems 2019, 4 (4), e00060-19 DOI: 10.1128/mSystems.00060-19Google ScholarThere is no corresponding record for this reference.
- 52Cimermancic, P.; Medema, M. H.; Claesen, J.; Kurita, K.; Brown, L. C. W.; Mavrommatis, K.; Pati, A.; Godfrey, P. A.; Koehrsen, M.; Clardy, J.; Birren, B. W.; Takano, E.; Sali, A.; Linington, R. G.; Fischbach, M. A. Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters. Cell 2014, 158 (2), 412– 421, DOI: 10.1016/j.cell.2014.06.034Google Scholar52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFyjtLfM&md5=de090354acacade81ebfb103e57200d5Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clustersCimermancic, Peter; Medema, Marnix H.; Claesen, Jan; Kurita, Kenji; Wieland Brown, Laura C.; Mavrommatis, Konstantinos; Pati, Amrita; Godfrey, Paul A.; Koehrsen, Michael; Clardy, Jon; Birren, Bruce W.; Takano, Eriko; Sali, Andrej; Linington, Roger G.; Fischbach, Michael A.Cell (Cambridge, MA, United States) (2014), 158 (2), 412-421CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Although biosynthetic gene clusters (BGCs) have been discovered for hundreds of bacterial metabolites, our knowledge of their diversity remains limited. Here, we used a novel algorithm to systematically identify BGCs in the extensive extant microbial sequencing data. Network anal. of the predicted BGCs revealed large gene cluster families, the vast majority uncharacterized. We exptl. characterized the most prominent family, consisting of two subfamilies of hundreds of BGCs distributed throughout the Proteobacteria; their products are aryl polyenes, lipids with an aryl head group conjugated to a polyene tail. We identified a distant relationship to a third subfamily of aryl polyene BGCs, and together the three subfamilies represent the largest known family of biosynthetic gene clusters, with more than 1000 members. Although these clusters are widely divergent in sequence, their small mol. products are remarkably conserved, indicating for the first time the important roles these compds. play in Gram-neg. cell biol.
- 53Buijs, Y.; Bech, P. K.; Vazquez-Albacete, D.; Bentzon-Tilia, M.; Sonnenschein, E. C.; Gram, L.; Zhang, S.-D. Marine Proteobacteria as a source of natural products: advances in molecular tools and strategies. Nat. Prod. Rep. 2019, 36 (9), 1333– 1350, DOI: 10.1039/C9NP00020HGoogle ScholarThere is no corresponding record for this reference.
- 54Baba, A.; Miyazaki, M.; Nagahama, T.; Nogi, Y. Microbulbifer chitinilyticus sp. nov. and Microbulbifer okinawensis sp. nov., chitin-degrading bacteria isolated from mangrove forests. Int. J. Syst. Evol. Microbiol. 2011, 61 (Pt 9), 2215– 2220, DOI: 10.1099/ijs.0.024158-0Google ScholarThere is no corresponding record for this reference.
- 55Miyazaki, M.; Nogi, Y.; Ohta, Y.; Hatada, Y.; Fujiwara, Y.; Ito, S.; Horikoshi, K. Microbulbifer agarilyticus sp. nov. and Microbulbifer thermotolerans sp. nov., agar-degrading bacteria isolated from deep-sea sediment. Int. J. Syst. Evol. Microbiol. 2008, 58, 1128– 1133, DOI: 10.1099/ijs.0.65507-0Google ScholarThere is no corresponding record for this reference.
- 56Vashist, P.; Nogi, Y.; Ghadi, S. C.; Verma, P.; Shouche, Y. S. Microbulbifer mangrovi sp. nov., a polysaccharide-degrading bacterium isolated from an Indian mangrove. Int. J. Syst. Evol. Microbiol. 2013, 63, 2532– 2537, DOI: 10.1099/ijs.0.042978-0Google ScholarThere is no corresponding record for this reference.
- 57González, J. M.; Mayer, F.; Moran, M. A.; Hodson, R. E.; Whitman, W. B. Microbulbifer hydrolyticus gen. nov., sp. nov., and Marinobacterium georgiense gen. nov., sp. nov., two marine bacteria from a lignin-rich pulp mill waste enrichment community. Int. J. Syst. Bacteriol. 1997, 47 (2), 369– 376, DOI: 10.1099/00207713-47-2-369Google ScholarThere is no corresponding record for this reference.
- 58Lee, Y. S. Isolation and Characterization of a Novel Cold-Adapted Esterase, MtEst45, from Microbulbifer thermotolerans DAU221. Front. Microbiol. 2016, 7, 218 DOI: 10.3389/fmicb.2016.00218Google ScholarThere is no corresponding record for this reference.
- 59Jayanetti, D. R.; Braun, D. R.; Barns, K. J.; Rajski, S. R.; Bugni, T. S. Bulbiferates A and B: Antibacterial Acetamidohydroxybenzoates from a Marine Proteobacterium, Microbulbifer sp. J. Nat. Prod. 2019, 82 (7), 1930– 1934, DOI: 10.1021/acs.jnatprod.9b00312Google ScholarThere is no corresponding record for this reference.
- 60Lu, S.; Zhang, Z.; Sharma, A. R.; Nakajima-Shimada, J.; Harunari, E.; Oku, N.; Trianto, A.; Igarashi, Y. Bulbiferamide, an Antitrypanosomal Hexapeptide Cyclized via an N-Acylindole Linkage from a Marine Obligate Microbulbifer. J. Nat. Prod. 2023, 86 (4), 1081– 1086, DOI: 10.1021/acs.jnatprod.2c01083Google Scholar60https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXjslKrsb0%253D&md5=6e69f4d0d21896f1ef828265d0fc69c1Bulbiferamide, an Antitrypanosomal Hexapeptide Cyclized via an N-Acylindole Linkage from a Marine Obligate MicrobulbiferLu, Shiyang; Zhang, Zhiwei; Sharma, Amit Raj; Nakajima-Shimada, Junko; Harunari, Enjuro; Oku, Naoya; Trianto, Agus; Igarashi, YasuhiroJournal of Natural Products (2023), 86 (4), 1081-1086CODEN: JNPRDF; ISSN:0163-3864. (American Chemical Society-American Society of Pharmacognosy)UV absorption spectroscopy-guided fractionation of the culture ext. of a marine obligate bacterium of the genus Microbulbifer yielded a novel cyclic hexapeptide, bulbiferamide. NMR spectroscopic and mass spectrometric analyses revealed the structure of bulbiferamide to be a cyclic tetrapeptide appending a ureido-bridged two amino acid unit. Notably, Trp is a junction residue, forming on one hand a very rare N-aminoacylated indole linkage for cyclization and on the other hand connecting the ureido-contg. tail structure, which is an unprecedented way of configuring peptides. The component amino acids were detd. to be L by the advanced Marfey's method. Bulbiferamide displayed growth inhibitory activity against Trypanosoma cruzi epimastigotes with an IC50 value of 4.1 μM, comparable to the currently approved drug benznidazole, while it was not cytotoxic to P388 murine leukemia cells at 100 μM.
- 61Zhong, W.; Deutsch, J. M.; Yi, D.; Abrahamse, N. H.; Mohanty, I.; Moore, S. G.; McShan, A. C.; Garg, N.; Agarwal, V. Discovery and Biosynthesis of Ureidopeptide Natural Products Macrocyclized via Indole N-acylation in Marine Microbulbifer spp. Bacteria. ChemBioChem 2023, 24 (12), e202300190 DOI: 10.1002/cbic.202300190Google Scholar61https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhtVSit73F&md5=928d657bc587255525a02b9b3815e585Discovery and Biosynthesis of Ureidopeptide Natural Products Macrocyclized via Indole N-acylation in Marine Microbulbifer spp. BacteriaZhong, Weimao; Deutsch, Jessica M.; Yi, Dongqi; Abrahamse, Nadine H.; Mohanty, Ipsita; Moore, Samuel G.; McShan, Andrew C.; Garg, Neha; Agarwal, VinayakChemBioChem (2023), 24 (12), e202300190CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)Commensal bacteria assocd. with marine invertebrates are underappreciated sources of chem. novel natural products. Using mass spectrometry, we had previously detected the presence of peptidic natural products in obligate marine bacteria of the genus Microbulbifer cultured from marine sponges. In this report, the isolation and structural characterization of a panel of ureidohexapeptide natural products, termed the bulbiferamides, from Microbulbifer strains is reported wherein the tryptophan side chain indole participates in a macrocyclizing peptide bond formation. Genome sequencing identifies biosynthetic gene clusters encoding prodn. of the bulbiferamides and implicates the involvement of a thioesterase in the indolic macrocycle formation. The structural diversity and widespread presence of bulbiferamides in commensal microbiomes of marine invertebrates point toward a possible ecol. role for these natural products.
- 62Zhong, W.; Aiosa, N.; Deutsch, J. M.; Garg, N.; Agarwal, V. Pseudobulbiferamides: Plasmid-Encoded Ureidopeptide Natural Products with Biosynthetic Gene Clusters Shared Among Marine Bacteria of Different Genera. J. Nat. Prod. 2023, 86 (10), 2414– 2420, DOI: 10.1021/acs.jnatprod.3c00595Google ScholarThere is no corresponding record for this reference.
- 63Zhong, W.; Agarwal, V. Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty. Beilstein J. Org. Chem. 2024, 20, 1635– 1651, DOI: 10.3762/bjoc.20.146Google ScholarThere is no corresponding record for this reference.
- 64Mawji, E.; Gledhill, M.; Milton, J. A.; Tarran, G. A.; Ussher, S.; Thompson, A.; Wolff, G. A.; Worsfold, P. J.; Achterberg, E. P. Hydroxamate siderophores: occurrence and importance in the Atlantic Ocean. Environ. Sci. Technol. 2008, 42 (23), 8675– 8680, DOI: 10.1021/es801884rGoogle Scholar64https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhtlWqurzI&md5=392e690d8a01954b78dd82fd9fb1dad2Hydroxamate Siderophores: Occurrence and Importance in the Atlantic OceanMawji, Edward; Gledhill, Martha; Milton, James A.; Tarran, Glen A.; Ussher, Simon; Thompson, Anu; Wolff, George A.; Worsfold, Paul J.; Achterberg, Eric P.Environmental Science & Technology (2008), 42 (23), 8675-8680CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)Siderophores are bacteria-produced chelates as part of a highly specific Fe uptake mechanism. They are thought to be important in the bacterial acquisition of Fe from seawater and affect Fe biogeochem. in the ocean. We have identified and quantified two types of siderophores in seawater samples collected from the Atlantic Ocean. The authors identified and quantified 2 types of siderophores in seawater collected from the Atlantic Ocean. These siderophores were identified as hydroxamate siderophores, both ferrioxamine species representative of the more sol. marine siderophores characterized to date. Ferrioxamine G is widely distributed in surface water throughout the Atlantic ferrioxamine E has a more varied distribution. Total concns. of these 2 siderophores is 3-20 pM in the euphotic zone. If these compds. are fully complexed in seawater, they represent ∼0.2-4.6% of the <0.2 μm Fe pool. Data confirmed siderophore-mediated Fe acquisition is important for marine heterotrophic bacteria and indicated siderophores play an important role in the oceanic biogeochem. Fe cycling.
- 65Boiteau, R. M.; Mende, D. R.; Hawco, N. J.; McIlvin, M. R.; Fitzsimmons, J. N.; Saito, M. A.; Sedwick, P. N.; DeLong, E. F.; Repeta, D. J. Siderophore-Based Microbial Adaptations to Iron Scarcity Across the Eastern Pacific Ocean. Proc. Natl. Acad. Sci. U.S.A. 2016, 113 (50), 14237– 14242, DOI: 10.1073/pnas.1608594113Google Scholar65https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvFOgs7rK&md5=7ad913c2e3a5ca860b8eb7431d4a91b4Siderophore-based microbial adaptations to iron scarcity across the eastern Pacific OceanBoiteau, Rene M.; Mende, Daniel R.; Hawco, Nicholas J.; McIlvin, Matthew R.; Fitzsimmons, Jessica N.; Saito, Mak A.; Sedwick, Peter N.; DeLong, Edward F.; Repeta, Daniel J.Proceedings of the National Academy of Sciences of the United States of America (2016), 113 (50), 14237-14242CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Nearly all iron dissolved in the ocean is complexed by strong org. ligands of unknown compn. The effect of ligand compn. on microbial iron acquisition is poorly understood, but amendment expts. using model ligands show they can facilitate or impede iron uptake depending on their identity. Here we show that siderophores, org. compds. synthesized by microbes to facilitate iron uptake, are a dynamic component of the marine ligand pool in the eastern tropical Pacific Ocean. Siderophore concns. in iron-deficient waters averaged 9 pM, up to fivefold higher than in iron-rich coastal and nutrient-depleted oligotrophic waters, and were dominated by amphibactins, amphiphilic siderophores with cell membrane affinity. Phylogenetic anal. of amphibactin biosynthetic genes suggests that the ability to produce amphibactins has transferred horizontally across multiple Gammaproteobacteria, potentially driven by pressures to compete for iron. In coastal and oligotrophic regions of the eastern Pacific Ocean, amphibactins were replaced with lower concns. (1-2 pM) of hydrophilic ferrioxamine siderophores. Our results suggest that org. ligand compn. changes across the surface ocean in response to environmental pressures. Hydrophilic siderophores are predominantly found across regions of the ocean where iron is not expected to be the limiting nutrient for the microbial community at large. However, in regions with intense competition for iron, some microbes optimize iron acquisition by producing siderophores that minimize diffusive losses to the environment. These siderophores affect iron bioavailability and thus may be an important component of the marine iron cycle.
- 66Deutsch, J. M.; Green, M. O.; Akavaram, P.; Davis, A. C.; Diskalkar, S. S.; Du Plessis, I. A.; Fallon, H. A.; Grason, E. M.; Kauf, E. G.; Kim, Z. M.; Miller, J. R.; Neal, A. L.; Riera, T.; Stroeva, S.-E.; Tran, J.; Tran, V.; Coronado, A. V.; Coronado, V. V.; Wall, B. T.; Yang, Cm.; Mohanty, I.; Abrahamse, N. H.; Freeman, C. J.; Easson, C. G.; Fiore, C. L.; Onstine, A. E.; Djeddar, N.; Biliya, S.; Bryksin, A. V.; Garg, N.; Agarwal, V. Limited Metabolomic Overlap between Commensal Bacteria and Marine Sponge Holobionts Revealed by Large Scale Culturing and Mass Spectrometry-Based Metabolomics: An Undergraduate Laboratory Pedagogical Effort at Georgia Tech. Mar. Drugs 2023, 21 (1), 53 DOI: 10.3390/md21010053Google ScholarThere is no corresponding record for this reference.
- 67Buijs, Y.; Isbrandt, T.; Zhang, S.-D.; Larsen, T. O.; Gram, L. The Antibiotic Andrimid Produced by Vibrio coralliilyticus Increases Expression of Biosynthetic Gene Clusters and Antibiotic Production in Photobacterium galatheae. Front. Microbiol. 2020, 11, 622055 DOI: 10.3389/fmicb.2020.622055Google ScholarThere is no corresponding record for this reference.
- 68Pluskal, T.; Castillo, S.; Villar-Briones, A.; Orešič, M. MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinf. 2010, 11 (1), 395 DOI: 10.1186/1471-2105-11-395Google Scholar68https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3cjjsVymsA%253D%253D&md5=e6e2ac996767f8526daccbdb7f4929e0MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile dataPluskal Tomas; Castillo Sandra; Villar-Briones Alejandro; Oresic MatejBMC bioinformatics (2010), 11 (), 395 ISSN:.BACKGROUND: Mass spectrometry (MS) coupled with online separation methods is commonly applied for differential and quantitative profiling of biological samples in metabolomic as well as proteomic research. Such approaches are used for systems biology, functional genomics, and biomarker discovery, among others. An ongoing challenge of these molecular profiling approaches, however, is the development of better data processing methods. Here we introduce a new generation of a popular open-source data processing toolbox, MZmine 2. RESULTS: A key concept of the MZmine 2 software design is the strict separation of core functionality and data processing modules, with emphasis on easy usability and support for high-resolution spectra processing. Data processing modules take advantage of embedded visualization tools, allowing for immediate previews of parameter settings. Newly introduced functionality includes the identification of peaks using online databases, MSn data support, improved isotope pattern support, scatter plot visualization, and a new method for peak list alignment based on the random sample consensus (RANSAC) algorithm. The performance of the RANSAC alignment was evaluated using synthetic datasets as well as actual experimental data, and the results were compared to those obtained using other alignment algorithms. CONCLUSIONS: MZmine 2 is freely available under a GNU GPL license and can be obtained from the project website at: http://mzmine.sourceforge.net/. The current version of MZmine 2 is suitable for processing large batches of data and has been applied to both targeted and non-targeted metabolomic analyses.
- 69Wang, M.; Carver, J. J.; Phelan, V. V.; Sanchez, L. M.; Garg, N.; Peng, Y.; Nguyen, D. D.; Watrous, J.; Kapono, C. A.; Luzzatto-Knaan, T.; Porto, C.; Bouslimani, A.; Melnik, A. V.; Meehan, M. J.; Liu, W.-T.; Crüsemann, M.; Boudreau, P. D.; Esquenazi, E.; Sandoval-Calderón, M.; Kersten, R. D.; Pace, L. A.; Quinn, R. A.; Duncan, K. R.; Hsu, C.-C.; Floros, D. J.; Gavilan, R. G.; Kleigrewe, K.; Northen, T.; Dutton, R. J.; Parrot, D.; Carlson, E. E.; Aigle, B.; Michelsen, C. F.; Jelsbak, L.; Sohlenkamp, C.; Pevzner, P.; Edlund, A.; McLean, J.; Piel, J.; Murphy, B. T.; Gerwick, L.; Liaw, C.-C.; Yang, Y.-L.; Humpf, H.-U.; Maansson, M.; Keyzers, R. A.; Sims, A. C.; Johnson, A. R.; Sidebottom, A. M.; Sedio, B. E.; Klitgaard, A.; Larson, C. B.; Boya P, C. A.; Torres-Mendoza, D.; Gonzalez, D. J.; Silva, D. B.; Marques, L. M.; Demarque, D. P.; Pociute, E.; O’Neill, E. C.; Briand, E.; Helfrich, E. J. N.; Granatosky, E. A.; Glukhov, E.; Ryffel, F.; Houson, H.; Mohimani, H.; Kharbush, J. J.; Zeng, Y.; Vorholt, J. A.; Kurita, K. L.; Charusanti, P.; McPhail, K. L.; Nielsen, K. F.; Vuong, L.; Elfeki, M.; Traxler, M. F.; Engene, N.; Koyama, N.; Vining, O. B.; Baric, R.; Silva, R. R.; Mascuch, S. J.; Tomasi, S.; Jenkins, S.; Macherla, V.; Hoffman, T.; Agarwal, V.; Williams, P. G.; Dai, J.; Neupane, R.; Gurr, J.; Rodríguez, A. M. C.; Lamsa, A.; Zhang, C.; Dorrestein, K.; Duggan, B. M.; Almaliti, J.; Allard, P.-M.; Phapale, P.; Nothias, L.-F.; Alexandrov, T.; Litaudon, M.; Wolfender, J.-L.; Kyle, J. E.; Metz, T. O.; Peryea, T.; Nguyen, D.-T.; VanLeer, D.; Shinn, P.; Jadhav, A.; Müller, R.; Waters, K. M.; Shi, W.; Liu, X.; Zhang, L.; Knight, R.; Jensen, P. R.; Palsson, B. Ø.; Pogliano, K.; Linington, R. G.; Gutiérrez, M.; Lopes, N. P.; Gerwick, W. H.; Moore, B. S.; Dorrestein, P. C.; Bandeira, N. Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nat. Biotechnol. 2016, 34 (8), 828– 837, DOI: 10.1038/nbt.3597Google Scholar69https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlaitLnE&md5=e6ca23ede2d85dd1460a5d73da542444Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular NetworkingWang, Mingxun; Carver, Jeremy J.; Phelan, Vanessa V.; Sanchez, Laura M.; Garg, Neha; Peng, Yao; Nguyen, Don Duy; Watrous, Jeramie; Kapono, Clifford A.; Luzzatto-Knaan, Tal; Porto, Carla; Bouslimani, Amina; Melnik, Alexey V.; Meehan, Michael J.; Liu, Wei-Ting; Crusemann, Max; Boudreau, Paul D.; Esquenazi, Eduardo; Sandoval-Calderon, Mario; Kersten, Roland D.; Pace, Laura A.; Quinn, Robert A.; Duncan, Katherine R.; Hsu, Cheng-Chih; Floros, Dimitrios J.; Gavilan, Ronnie G.; Kleigrewe, Karin; Northen, Trent; Dutton, Rachel J.; Parrot, Delphine; Carlson, Erin E.; Aigle, Bertrand; Michelsen, Charlotte F.; Jelsbak, Lars; Sohlenkamp, Christian; Pevzner, Pavel; Edlund, Anna; McLean, Jeffrey; Piel, Jorn; Murphy, Brian T.; Gerwick, Lena; Liaw, Chih-Chuang; Yang, Yu-Liang; Humpf, Hans-Ulrich; Maansson, Maria; Keyzers, Robert A.; Sims, Amy C.; Johnson, Andrew R.; Sidebottom, Ashley M.; Sedio, Brian E.; Klitgaard, Andreas; Larson, Charles B.; Boya P, Cristopher A.; Torres-Mendoza, Daniel; Gonzalez, David J.; Silva, Denise B.; Marques, Lucas M.; Demarque, Daniel P.; Pociute, Egle; O'Neill, Ellis C.; Briand, Enora; Helfrich, Eric J. N.; Granatosky, Eve A.; Glukhov, Evgenia; Ryffel, Florian; Houson, Hailey; Mohimani, Hosein; Kharbush, Jenan J.; Zeng, Yi; Vorholt, Julia A.; Kurita, Kenji L.; Charusanti, Pep; McPhail, Kerry L.; Nielsen, Kristian Fog; Vuong, Lisa; Elfeki, Maryam; Traxler, Matthew F.; Engene, Niclas; Koyama, Nobuhiro; Vining, Oliver B.; Baric, Ralph; Silva, Ricardo R.; Mascuch, Samantha J.; Tomasi, Sophie; Jenkins, Stefan; Macherla, Venkat; Hoffman, Thomas; Agarwal, Vinayak; Williams, Philip G.; Dai, Jingqui; Neupane, Ram; Gurr, Joshua; Rodriguez, Andres M. C.; Lamsa, Anne; Zhang, Chen; Dorrestein, Kathleen; Duggan, Brendan M.; Almaliti, Jehad; Allard, Pierre-Marie; Phapale, Prasad; Nothias, Louis-Felix; Alexandrov, Theodore; Litaudon, Marc; Wolfender, Jean-Luc; Kyle, Jennifer E.; Metz, Thomas O.; Peryea, Tyler; Nguyen, Dac-Trung; Van Leer, Danielle; Shinn, Paul; Jadhav, Ajit; Muller, Rolf; Waters, Katrina M.; Shi, Wenyuan; Liu, Xueting; Zhang, Lixin; Knight, Rob; Jensen, Paul R.; Palsson, Bernhard O.; Pogliano, Kit; Linington, Roger G.; Gutierrez, Marcelino; Lopes, Norberto P.; Gerwick, William H.; Moore, Bradley S.; Dorrestein, Pieter C.; Bandeira, NunoNature Biotechnology (2016), 34 (8), 828-837CODEN: NABIF9; ISSN:1087-0156. (Nature Publishing Group)The potential of the diverse chemistries present in natural products (NP) for biotechnol. and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry (MS) techniques are well-suited to high-throughput characterization of NP, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social Mol. Networking (GNPS; http://gnps.ucsd.edu), an open-access knowledge base for community-wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS, crowdsourced curation of freely available community-wide ref. MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of 'living data' through continuous reanal. of deposited data.
- 70Shannon, P.; Markie, A.; Ozier, O.; Baliga, N. S.; Wang, J. T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks. Genome Res. 2003, 13, 2498– 2504, DOI: 10.1101/gr.1239303Google Scholar70https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXovFWrtr4%253D&md5=2bcbca9a3bd04717761f0424c0209e43Cytoscape: A software environment for integrated models of biomolecular interaction networksShannon, Paul; Markiel, Andrew; Ozier, Owen; Baliga, Nitin S.; Wang, Jonathan T.; Ramage, Daniel; Amin, Nada; Schwikowski, Benno; Ideker, TreyGenome Research (2003), 13 (11), 2498-2504CODEN: GEREFS; ISSN:1088-9051. (Cold Spring Harbor Laboratory Press)Cytoscape is an open source software project for integrating biomol. interaction networks with high-throughput expression data and other mol. states into a unified conceptual framework. Although applicable to any system of mol. components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other mol. states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of addnl. computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined phys./functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
- 71Khan, A.; Mathelier, A. Intervene: a tool for intersection and visualization of multiple gene or genomic region sets. BMC Bioinf. 2017, 18 (1), 287 DOI: 10.1186/s12859-017-1708-7Google ScholarThere is no corresponding record for this reference.
- 72Dührkop, K.; Fleischauer, M.; Ludwig, M.; Aksenov, A. A.; Melnik, A. V. SIRIUS 4: A Rapid Tool for Turning Tandem Mass Spectra into Metabolite Structure Information. Nat. Methods 2019, 16, 299– 302, DOI: 10.1038/s41592-019-0344-8Google Scholar72https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmslKgurg%253D&md5=9f47c714d2412974315fcde740227da3SIRIUS 4: a rapid tool for turning tandem mass spectra into metabolite structure informationDuehrkop, Kai; Fleischauer, Markus; Ludwig, Marcus; Aksenov, Alexander A.; Melnik, Alexey V.; Meusel, Marvin; Dorrestein, Pieter C.; Rousu, Juho; Boecker, SebastianNature Methods (2019), 16 (4), 299-302CODEN: NMAEA3; ISSN:1548-7091. (Nature Research)Mass spectrometry is a predominant exptl. technique in metabolomics and related fields, but metabolite structural elucidation remains highly challenging. We report SIRIUS 4 (https://bio.informatik.uni-jena.de/sirius/), which provides a fast computational approach for mol. structure identification. SIRIUS 4 integrates CSI:FingerID for searching in mol. structure databases. Using SIRIUS 4, we achieved identification rates of more than 70% on challenging metabolomics datasets.
- 73Dührkop, K.; Nothias, L.-F.; Fleischauer, M.; Reher, R.; Ludwig, M.; Hoffmann, M. A.; Petras, D.; Gerwick, W. H.; Rousu, J.; Dorrestein, P. C.; Böcker, S. Systematic Classification of Unknown Metabolites Using High-Resolution Fragmentation Mass Spectra. Nat. Biotechnol. 2021, 39, 462– 471, DOI: 10.1038/s41587-020-0740-8Google Scholar73https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXisVSlu7jK&md5=120b8fd8fe78db3c2623391833b3bd32Systematic classification of unknown metabolites using high-resolution fragmentation mass spectraDuehrkop, Kai; Nothias, Louis-Felix; Fleischauer, Markus; Reher, Raphael; Ludwig, Marcus; Hoffmann, Martin A.; Petras, Daniel; Gerwick, William H.; Rousu, Juho; Dorrestein, Pieter C.; Boecker, SebastianNature Biotechnology (2021), 39 (4), 462-471CODEN: NABIF9; ISSN:1087-0156. (Nature Portfolio)Metabolomics using nontargeted tandem mass spectrometry can detect thousands of mols. in a biol. sample. However, structural mol. annotation is limited to structures present in libraries or databases, restricting anal. and interpretation of exptl. data. Here we describe CANOPUS (class assignment and ontol. prediction using mass spectrometry), a computational tool for systematic compd. class annotation. CANOPUS uses a deep neural network to predict 2,497 compd. classes from fragmentation spectra, including all biol. relevant classes. CANOPUS explicitly targets compds. for which neither spectral nor structural ref. data are available and predicts classes lacking tandem mass spectrometry training data. In evaluation using ref. data, CANOPUS reached very high prediction performance (av. accuracy of 99.7% in cross-validation) and outperformed four baseline methods. We demonstrate the broad utility of CANOPUS by investigating the effect of microbial colonization in the mouse digestive system, through anal. of the chemodiversity of different Euphorbia plants and regarding the discovery of a marine natural product, revealing biol. insights at the compd. class level.
- 74van der Hooft, J. J. J.; Wandy, J.; Barrett, M. P.; Burgess, K. E. V.; Rogers, S. Topic modeling for untargeted substructure exploration in metabolomics. Proc. Natl. Acad. Sci. U.S.A. 2016, 113 (48), 13738– 13743, DOI: 10.1073/pnas.1608041113Google Scholar74https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2snntlKntQ%253D%253D&md5=ac0b3c57ed44886cbc2d969522548e34Topic modeling for untargeted substructure exploration in metabolomicsvan der Hooft Justin Johan Jozias; Wandy Joe; Barrett Michael P; Burgess Karl E V; Rogers Simon; van der Hooft Justin Johan Jozias; Wandy Joe; Rogers Simon; Barrett Michael PProceedings of the National Academy of Sciences of the United States of America (2016), 113 (48), 13738-13743 ISSN:.The potential of untargeted metabolomics to answer important questions across the life sciences is hindered because of a paucity of computational tools that enable extraction of key biochemically relevant information. Available tools focus on using mass spectrometry fragmentation spectra to identify molecules whose behavior suggests they are relevant to the system under study. Unfortunately, fragmentation spectra cannot identify molecules in isolation but require authentic standards or databases of known fragmented molecules. Fragmentation spectra are, however, replete with information pertaining to the biochemical processes present, much of which is currently neglected. Here, we present an analytical workflow that exploits all fragmentation data from a given experiment to extract biochemically relevant features in an unsupervised manner. We demonstrate that an algorithm originally used for text mining, latent Dirichlet allocation, can be adapted to handle metabolomics datasets. Our approach extracts biochemically relevant molecular substructures ("Mass2Motifs") from spectra as sets of co-occurring molecular fragments and neutral losses. The analysis allows us to isolate molecular substructures, whose presence allows molecules to be grouped based on shared substructures regardless of classical spectral similarity. These substructures, in turn, support putative de novo structural annotation of molecules. Combining this spectral connectivity to orthogonal correlations (e.g., common abundance changes under system perturbation) significantly enhances our ability to provide mechanistic explanations for biological behavior.
- 75van Santen, J. A.; Jacob, G.; Singh, A. L.; Aniebok, V.; Balunas, M. J.; Bunsko, D.; Neto, F. C.; Castaño-Espriu, L.; Chang, C.; Clark, T. N.; Cleary Little, J. L.; Delgadillo, D. A.; Dorrestein, P. C.; Duncan, K. R.; Egan, J. M.; Galey, M. M.; Haeckl, F. P. J.; Hua, A.; Hughes, A. H.; Iskakova, D.; Khadilkar, A.; Lee, J.-H.; Lee, S.; LeGrow, N.; Liu, D. Y.; Macho, J. M.; McCaughey, C. S.; Medema, M. H.; Neupane, R. P.; O’Donnell, T. J.; Paula, J. S.; Sanchez, L. M.; Shaikh, A. F.; Soldatou, S.; Terlouw, B. R.; Tran, T. A.; Valentine, M.; van der Hooft, J. J. J.; Vo, D. A.; Wang, M.; Wilson, D.; Zink, K. E.; Linington, R. G. The Natural Products Atlas: An Open Access Knowledge Base for Microbial Natural Products Discovery. ACS Cent. Sci. 2019, 5 (11), 1824– 1833, DOI: 10.1021/acscentsci.9b00806Google Scholar75https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitFCit73P&md5=1ebc951ca96d93dd36d65dd8b3b3ad67The Natural Products Atlas: An Open Access Knowledge Base for Microbial Natural Products Discoveryvan Santen, Jeffrey A.; Jacob, Gregoire; Singh, Amrit Leen; Aniebok, Victor; Balunas, Marcy J.; Bunsko, Derek; Neto, Fausto Carnevale; Castano-Espriu, Laia; Chang, Chen; Clark, Trevor N.; Cleary Little, Jessica L.; Delgadillo, David A.; Dorrestein, Pieter C.; Duncan, Katherine R.; Egan, Joseph M.; Galey, Melissa M.; Haeckl, F. P. Jake; Hua, Alex; Hughes, Alison H.; Iskakova, Dasha; Khadilkar, Aswad; Lee, Jung-Ho; Lee, Sanghoon; LeGrow, Nicole; Liu, Dennis Y.; Macho, Jocelyn M.; McCaughey, Catherine S.; Medema, Marnix H.; Neupane, Ram P.; ODonnell, Timothy J.; Paula, Jasmine S.; Sanchez, Laura M.; Shaikh, Anam F.; Soldatou, Sylvia; Terlouw, Barbara R.; Tran, Tuan Anh; Valentine, Mercia; van der Hooft, Justin J. J.; Vo, Duy A.; Wang, Mingxun; Wilson, Darryl; Zink, Katherine E.; Linington, Roger G.ACS Central Science (2019), 5 (11), 1824-1833CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)Despite rapid evolution in the area of microbial natural products chem., there is currently no open access database contg. all microbially produced natural product structures. Lack of availability of these data is preventing the implementation of new technologies in natural products science. Specifically, development of new computational strategies for compd. characterization and identification are being hampered by the lack of a comprehensive database of known compds. against which to compare exptl. data. The creation of an open access, community-maintained database of microbial natural product structures would enable the development of new technologies in natural products discovery, and improve the interoperability of existing natural products data resources. However, these data are spread unevenly throughout the historical scientific literature, including both journal articles and international patents. These documents have no std. format, are often not digitized as machine readable text, and are not publicly available. Further, none of these documents have assocd. structure files (e.g., MOL, InChI, or SMILES), instead contg. images of structures. This makes extn. and formatting of relevant natural products data a formidable challenge. Using a combination of manual curation and automated data mining approaches we have created a database of microbial natural products (The Natural Products Atlas, www.npatlas.org) that includes 24,594 compds. and contains referenced data for structure, compd. names, source organisms, isolation refs., total syntheses and instances of structural reassignment. This database is accompanied by an interactive web portal that permits searching by structure, substructure, and phys. properties. The Web site also provides mechanisms for visualizing natural products chem. space, and dashboards for displaying author and discovery timeline data. These interactive tools offer a powerful knowledge base for natural products discovery with a central interface for structure and property-based searching, and presents new viewpoints on structural diversity in natural products. The Natural Products Atlas has been developed under FAIR principles (Findable, Accessible, Interoperable, and Reusable) and is integrated with other emerging natural product databases, including the Min. Information About a Biosynthetic Gene Cluster (MIBiG) repository, and the Global Natural Products Social Mol. Networking (GNPS) platform. It is designed as a community-supported resource to provide a central repository for known natural product structures from microorganisms, and is the 1st comprehensive, open access resource of this type. It is expected that the Natural Products Atlas will enable the development of new natural products discovery modalities and accelerate the process of structural characterization for complex natural products libraries. The Natural Products Atlas is a new online database of microbially derived natural product structures, designed as a comprehensive open access repository for the scientific community.
- 76MarinLit. A Database of the Marine Natural Products Literature, Royal Society of Chemistry http://pubs.rsc.org/marinlit/. (accessed January 20, 2023).Google ScholarThere is no corresponding record for this reference.
- 77Al Shaer, D.; Al Musaimi, O.; de la Torre, B. G.; Albericio, F. Hydroxamate siderophores: Natural occurrence, chemical synthesis, iron binding affinity and use as Trojan horses against pathogens. Eur. J. Med. Chem. 2020, 208, 112791 DOI: 10.1016/j.ejmech.2020.112791Google Scholar77https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVynurfI&md5=5ac6f84332f643caede5b195cef1b835Hydroxamate siderophores: Natural occurrence, chemical synthesis, iron binding affinity and use as Trojan horses against pathogensAl Shaer, Danah; Al Musaimi, Othman; de la Torre, Beatriz G.; Albericio, FernandoEuropean Journal of Medicinal Chemistry (2020), 208 (), 112791CODEN: EJMCA5; ISSN:0223-5234. (Elsevier Masson SAS)A review. Hydroxamic acids are an important class of mols., in particular because of their metal-chelating ability. Microorganisms, including pathogenic bacteria, use hydroxamate-based entities (siderophores), among others, to acquire Fe (III). The "Trojan horse" strategy exploits the need of bacteria for this metal by using Fe (III) active transporters to carry antibacterial or bactericidal moieties into the bacterial cell. Many natural Trojan horses (sideromycins) are derived from hydroxamic acids, thereby reflecting their potency. Various artificial sideromycins and their antibacterial activities have been reported. This review discusses the structural aspects of the hydroxamate-siderophores isolated in the last two decades, the chem. synthesis of their building blocks, their binding affinity towards Fe (III), and their application as Trojan horses (weaknesses and strengths).
- 78Martinez, J. S.; Carter-Franklin, J. N.; Mann, E. L.; Martin, J. D.; Haygood, M. G.; Butler, A. Structure and membrane affinity of a suite of amphiphilic siderophores produced by a marine bacterium. Proc. Natl. Acad. Sci. U.S.A. 2003, 100 (7), 3754– 3759, DOI: 10.1073/pnas.0637444100Google Scholar78https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXivFSqsbs%253D&md5=f97cddc20add56b20664316273764d9eStructure and membrane affinity of a suite of amphiphilic siderophores produced by a marine bacteriumMartinez, Jennifer S.; Carter-Franklin, Jayme N.; Mann, Elizabeth L.; Martin, Jessica D.; Haygood, Margo G.; Butler, AlisonProceedings of the National Academy of Sciences of the United States of America (2003), 100 (7), 3754-3759CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Iron concns. in the ocean are low enough to limit the growth of marine microorganisms, which raises questions about the mol. mechanisms these organisms use to acquire iron. Marine bacteria have been shown to produce siderophores to facilitate iron(III) uptake. We describe the structures of a suite of amphiphilic siderophores, named the amphibactins, which are produced by a nearshore isolate, γ Proteobacterium, Vibrio sp. R-10. Each amphibactin has the same Tris-hydroxamate-contg. peptidic headgroup composed of three ornithine residues and one serine residue but differs in the acyl appendage, which ranges from C-14 to C-18 and varies in the degree of satn. and hydroxylation. Although amphiphilic siderophores are relatively rare, cell-assocd. amphiphilic siderophores are even less common. We find that the amphibactins are cell-assocd. siderophores. As a result of the variation in the nature of the fatty acid appendage and the cellular location of the amphibactins, the membrane partitioning of these siderophores was investigated. The physiol. mixt. of amphibactins had a range of membrane affinities (3.8 × 103 to 8.3 × 102 M-1) that are larger overall than other amphiphilic siderophores, likely accounting for their cell assocn. This cell assocn. is likely an important defense against siderophore diffusion in the oceanic environment. The phylogenetic affiliation of Vibrio sp. R-10 is discussed, as well as the obsd. predominance of amphiphilic siderophores produced by marine bacteria in contrast to those produced by terrestrial bacteria.
- 79Walker, L. R.; Tfaily, M. M.; Shaw, J. B.; Hess, N. J.; Paša-Tolić, L.; Koppenaal, D. W. Unambiguous identification and discovery of bacterial siderophores by direct injection 21 T Fourier transform ion cyclotron resonance mass spectrometry. Metallomics 2017, 9 (1), 82– 92, DOI: 10.1039/C6MT00201CGoogle Scholar79https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitVWqu77I&md5=2ddad7a08c033090c4bad1037b8c9c14Unambiguous identification and discovery of bacterial siderophores by direct injection 21 Tesla Fourier transform ion cyclotron resonance mass spectrometryWalker, Lawrence R.; Tfaily, Malak M.; Shaw, Jared B.; Hess, Nancy J.; Pasa-Tolic, Ljiljana; Koppenaal, David W.Metallomics (2017), 9 (1), 82-92CODEN: METAJS; ISSN:1756-591X. (Royal Society of Chemistry)Under iron-limiting conditions, bacteria produce low mol. mass Fe(iii) binding mols. known as siderophores to sequester the Fe(iii), along with other elements, increasing their bioavailability. Siderophores are thought to influence iron cycling and biogeochem. in both marine and terrestrial ecosystems and hence the need for rapid, confident characterization of these compds. has increased. In this study, the type of siderophores produced by two marine bacterial species, Synechococcus sp. PCC 7002 and Vibrio cyclitrophicus 1F53, were characterized by use of a newly developed 21 T Fourier-transform ion cyclotron resonance mass spectrometer (FTICR MS) with direct injection electrospray ionization. This technique allowed for the rapid detection of synechobactins from Synechococcus sp. PCC 7002 as well as amphibactins from Vibrio cyclitrophicus 1F53 based on high mass accuracy and resoln. allowing for observation of specific Fe isotopes and isotopic fine structure enabling highly confident identification of these siderophores. When combined with mol. network anal. two new amphibactins were discovered and verified by tandem MS. These results show that high-field FTICR MS is a powerful technique that will greatly improve the ability to rapidly identify and discover metal binding species in the environment.
- 80Pérez-Miranda, S.; Cabirol, N.; George-Téllez, R.; Zamudio-Rivera, L. S.; Fernández, F. J. O-CAS, a fast and universal method for siderophore detection. J. Microbiol. Methods 2007, 70 (1), 127– 131, DOI: 10.1016/j.mimet.2007.03.023Google Scholar80https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXmvVKmu74%253D&md5=70124c1ff07c8c607680221459c41b97O-CAS, a fast and universal method for siderophore detectionPerez-Miranda, S.; Cabirol, N.; George-Tellez, R.; Zamudio-Rivera, L. S.; Fernandez, F. J.Journal of Microbiological Methods (2007), 70 (1), 127-131CODEN: JMIMDQ; ISSN:0167-7012. (Elsevier B.V.)In this work, the popular CAS assay for siderophore detection, based on the utilization of chrome azurol S, was redesigned and optimized to produce a new, fast, non-toxic, and easy method to det. a wide variety of microorganisms capable of siderophore prodn. on a solid medium. Furthermore, this specific bioassay allows for the identification of more than one single siderophore-producing microorganism at the same time, using an overlay technique in which a modified CAS medium is cast upon culture agar plates (thus its name "O-CAS", for overlaid CAS). Detection was optimized through adjustments to the medium's compn. and a quantifying strategy. Specificity of the bioassay was tested on microorganisms known for siderophore prodn. As a result, a total of 48 microorganisms were isolated from three different types of samples (fresh water, salt water, and alk. soil), of which 36 were detd. as siderophore producers. The compds. identified through this method belonged to both hydroxamate and catechol-types, previously reported to cause color change of the CAS medium from blue to orange and purple, resp. Some isolated microorganisms, however, caused a color change that differed from previous descriptions.
- 81Raines, D. J.; Sanderson, T. J.; Wilde, E. J.; Duhme-Klair, A. K. Siderophores. In Reference Module in Chemistry, Molecular Sciences and Chemical Engineering; Elsevier, 2015.Google ScholarThere is no corresponding record for this reference.
- 82Hou, Z.; Raymond, K. N.; O’Sulliva, B.; Esker, T. W.; Nishio, T. A Preorganized Siderophore: Thermodynamic and Structural Characterization of Alcaligin and Bisucaberin, Microbial Macrocyclic Dihydroxamate Chelating Agents1. Inorg. Chem. 1998, 37 (26), 6630– 6637, DOI: 10.1021/ic9810182Google Scholar82https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXnsFKnsL4%253D&md5=29e4130272fe191f38587469c4980b9dA Preorganized Siderophore: Thermodynamic and Structural Characterization of Alcaligin and Bisucaberin, Microbial Macrocyclic Dihydroxamate Chelating AgentsHou, Zhiguo; Raymond, Kenneth N.; O'Sullivan, Brendon; Esker, Todd W.; Nishio, TakayukiInorganic Chemistry (1998), 37 (26), 6630-6637CODEN: INOCAJ; ISSN:0020-1669. (American Chemical Society)The Fe coordination chem. of two macrocyclic dihydroxamate siderophores, alcaligin (AG) and bisucaberin (BR), was studied thermodynamically and structurally. Alcaligin is a siderophore of freshwater bacteria as well as mammalian pathogens, including the bacterium that causes whooping cough in humans, while bisucaberin, a structural analog of alcaligin, is produced by marine bacteria. Both alcaligin and bisucaberin form 1:1 ferric complexes (FeL+) in acidic conditions and 2:3 ferric complexes (Fe2L3) at and above neutral pH. The stability consts. of these macrocyclic dihydroxamate siderophores differ significantly from that of rhodotorulic acid (RA), a linear dihydroxamate siderophore. Notably, KFeL of alcaligin is 32 times greater than that of rhodotorulic acid, while the subsequent stepwise formation const. for Fe2L3 is 3 times less. The Fe(III) complexes of alcaligin are stereospecific; the abs. configuration of the Fe2L3 complex (CD and x-ray structure) is Λ. The structure of the Fe2L3 alcaligin complex is a topol. alternative to the triple-helicate structure of the rhodotorulic complex Fe2(RA)3. The structures of the free ligand and the bisbidentate ligand in the FeL complex are essentially identical, indicating that alcaligin is highly preorganized for metal ion binding. This explains the difference in KFeL between alcaligin and rhodotorulic acid, as well as explaining the monobridged topol. of the Fe2L3 alcaligin complex. The protonation consts. (log Ka1 and log Ka2) are 9.42(5) and 8.61(1) for alcaligin and 9.49(2) and 8.76(3) for bisucaberin. The stepwise formation consts. of the Fe(III) complexes (log KML and log KM2L3) are 23.5(2) and 17.7(2) for alcaligin and 23.5(5) and 17.2(5) for bisucaberin. The overall formation consts. (log β230) of alcaligin and bisucaberin are 64.7(1) and 64.3(1). The soln. chem. of Fe(III) and alcaligin was further studied at a lower ligand to metal ratio (1:1). At high pH, a novel 2:2 ferric bis-μ-oxo-bridged complex of alcaligin forms (Fe2L2O22-) with a log β22-4 of 16.7(2). This species exhibits behavior consistent with an Fe bis-μ-oxo complex, including antiferromagnetic coupling. Fe2(AG)3·25H2O crystallizes in the orthorhombic space group P212121 with a 13.3374(4), b 16.1879(5), c 37.886(1) Å, V = 8179.7(4), Z = 4, final R (Rw) = 0.053(0.068).
- 83Harris, W. R.; Carrano, C. J.; Raymond, K. N. Coordination chemistry of microbial iron transport compounds. 16. Isolation, characterization, and formation constants of ferric aerobactin. J. Am. Chem. Soc. 1979, 101 (10), 2722– 2727, DOI: 10.1021/ja00504a038Google Scholar83https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE1MXkvVGrsbg%253D&md5=5fffdb06f632741d94b80c99eb5331c7Coordination chemistry of microbial iron transport compounds. 16. Isolation, characterization, and formation constants of ferric aerobactinHarris, Wesley R.; Carrano, Carl J.; Raymond, Kenneth N.Journal of the American Chemical Society (1979), 101 (10), 2722-7CODEN: JACSAT; ISSN:0002-7863.Aerobactin, a dihydroxamate deriv. of citric acid, is a siderophore produced by Aerobacter aerogenes. The Fe complex was isolated from neutral aq. solns. as the trisodium salt. The high-spin octahedral complex was formed using the 2 bidentate hydroxamate groups and the central carboxylate and hydroxyl moieties of the citrate backbone. Ferric aerobactin exists predominantly as the Λ optical isomer in aq. solns. The stability consts. (logβ113 = 31.74, log β112 = 29.70, log β111 = 26.68, log β110 = 23.06, logβ11‾1 = 18.48) and redox potential also were detd. from spectroscopic, potentiometric titrn., and electrochem. techniques. The implication of these results to the mechanism of Fe uptake and release by A. aerogenes is discussed.
- 84Ito, T.; Neilands, J. B. Products of “Low-iron Fermentation” with Bacillus subilis: Isolation, Characterization and Synthesis of 2,3-Dihydroxybenzoylglycine1,2. J. Am. Chem. Soc. 1958, 80 (17), 4645– 4647, DOI: 10.1021/ja01550a058Google Scholar84https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaG1MXivFeqsA%253D%253D&md5=0cce30ee41e36a134f885e500f9d95edProducts of low-iron fermentation with Bacillus subtilis: isolation, characterization, and synthesis of 2,3-dihydroxybenzoylglycineIto, Takeru; Neilands, J. B.Journal of the American Chemical Society (1958), 80 (), 4645-7CODEN: JACSAT; ISSN:0002-7863.cf. C.A. 51, 14004i. The phenolic acid produced by B. subtilis NRRL B-1471 in Fe deficiency was crystd. and identified by synthesis as 2,3-dihydroxybenzoylglycine (I); synthetic I was indistinguishable from natural I by paper chromatography in various systems, color reactions with FeCl3, reaction with HNO2, soly., ultraviolet spectrum, infrared spectrum, apparent pKa values, and mol. wt. 2,3-(HO)2C6H3CO2H (1 g.) and 0.7-0.8 g. glycine Et ester in 5-6 ml. tetrahydrofuran (THF) treated with 1.5 g. dicyclohexylcarbodiimide in 3-5 ml. THF, the mixt. held overnight at room temp. under N, a small amt. of AcOH added, the soln. filtered, the solvent evapd., the residue dissolved in EtOAc, washed with dil. HCl, the EtOAc evapd., the residue stirred 4 hrs. at room temp. under N in 20-30 ml. N NaOH, filtered, the filtrate acidified with 4-6 ml. dil. H2SO4, extd. with EtOAc, the solvent evapd. to dryness, and the residue in dil. NH4OH treated (ice bath) with dil. HCl yielded 500 mg. I, m. 210-11°.
- 85Barghouthi, S.; Young, R.; Olson, M. O.; Arceneaux, J. E.; Clem, L. W.; Byers, B. R. Amonabactin, a novel tryptophan- or phenylalanine-containing phenolate siderophore in Aeromonas hydrophila. J. Bacteriol. 1989, 171 (4), 1811– 1816, DOI: 10.1128/jb.171.4.1811-1816.1989Google ScholarThere is no corresponding record for this reference.
- 86Atkin, C. L.; Neilands, J. B. Rhodotorulic acid, a diketopiperazine dihydroxamic acid with growth-factor activity. I. Isolation and characterization. Biochemistry 1968, 7 (10), 3734– 3739, DOI: 10.1021/bi00850a054Google Scholar86https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF1MXhtVSn&md5=52982880fd8eae737b0cd9aaaeff7af9Rhodotorulic acid, a diketopiperazine dihydroxamic acid with growth-factor activity. I. Isolation and characterizationAtkin, Curtis L.; Neilands, J. B.Biochemistry (1968), 7 (10), 3734-9CODEN: BICHAW; ISSN:0006-2960.A strongly Fe(III)-binding compd. with the properties of a secondary hydroxamic acid was isolated from supernatants of Fe-deficient cultures of a red yeast, subsequently identified as Rhodotorula pilimaniae. The name rhodotorulic acid was selected inasmuch as a no. of Rhodotorula species produce the compound in low Fe media. It was characterized by degradation, spectral properties, and synthetic expts. as LL-3,6-bis(N-acetyl-3-hydroxyaminopropyl)-2,5-piperazinedione, i.e., the diketopiperazine of δ-N-acetyl-L-δ-N-hydroxyornithine, which amino acid is a constituent of ferrichromes, albomycins, and fusarinines. The analogous diketopiperazine of δ-N-acetyl-L-ornithine was identical with a redn. product of rhodotorulic acid. Rhodotorulic acid has biol. activity comparable with that of schizokinen in Lankford's Bacillus test system (Byers, et al., 1967). It also shows potent growth-factor activity in assays with Arthrobacter species, although lacking the antagonistic effect of other sideramine growth factors on albomycin inhibition of bacterial growth.
- 87Spasojević, I.; Boukhalfa, H.; Stevens, R. D.; Crumbliss, A. L. Aqueous Solution Speciation of Fe(III) Complexes with Dihydroxamate Siderophores Alcaligin and Rhodotorulic Acid and Synthetic Analogues Using Electrospray Ionization Mass Spectrometry. Inorg. Chem. 2001, 40 (1), 49– 58, DOI: 10.1021/ic991390xGoogle ScholarThere is no corresponding record for this reference.
- 88Xu, G.; Martinez, J. S.; Groves, J. T.; Butler, A. Membrane Affinity of the Amphiphilic Marinobactin Siderophores. J. Am. Chem. Soc. 2002, 124 (45), 13408– 13415, DOI: 10.1021/ja026768wGoogle Scholar88https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XotVegtrg%253D&md5=a0dde8ef0fbecc71e02ec4fd10f668baMembrane Affinity of the Amphiphilic Marinobactin SiderophoresXu, Guofeng; Martinez, Jennifer S.; Groves, John T.; Butler, AlisonJournal of the American Chemical Society (2002), 124 (45), 13408-13415CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Marinobactins are a class of newly discovered marine bacterial siderophores with a unique amphiphilic structure, suggesting that their functions relate to interactions with cell membranes. Here we use small and large unilamellar L-α-dimyristoylphosphatidylcholine vesicles (SUVs and LUVs) as model membranes to examine the thermodn. and kinetics of the membrane binding of marinobactins, particularly marinobactin E (apo-ME) and its iron(III) complex, Fe-ME. Siderophore-membrane interactions are characterized by NMR line broadening, stopped-flow spectrophotometry, fluorescence quenching, and ultracentrifugation. It is detd. that apo-ME has a strong affinity for lipid membranes with molar fraction partition coeffs. Kxapo-ME = 6.3×105 for SUVs and 3.6×105 for LUVs. This membrane assocn. is shown to cause only a 2-fold decrease in the rate of iron(III) binding by apo-ME. However, upon the formation of the iron(III) complex Fe-ME, the membrane affinity of the siderophore decreased substantially (KxFe-ME = 1.3×104 for SUVs and 9.6×103 for LUVs). The kinetics of membrane binding and dissocn. by Fe-ME were also detd. (konFe-ME = 1.01 M-1 s-1; koffFe-ME = 4.4×10-3 s-1). The suite of marinobactins with different fatty acid chain lengths and degrees of chain unsatn. showed a range of membrane affinities (5.8×103 to 36 M-1). The affinity that marinobactins exhibit for membranes and the changes obsd. upon iron binding could provide unique biol. advantages in a receptor-assisted iron acquisition process in which loss of the iron-free siderophore by diffusion is limited by the strong assocn. with the lipid phase.
- 89Harrington, J. M.; Crumbliss, A. L. The redox hypothesis in siderophore-mediated iron uptake. BioMetals 2009, 22 (4), 679– 689, DOI: 10.1007/s10534-009-9233-4Google Scholar89https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXotFCisrs%253D&md5=bd753fb87d6736aa7ca07f39afc3ca45The redox hypothesis in siderophore-mediated iron uptakeHarrington, James M.; Crumbliss, Alvin L.BioMetals (2009), 22 (4), 679-689CODEN: BOMEEH; ISSN:0966-0844. (Springer)A review. The viability of iron(III/II) redn. as the initial step in the in vivo release of iron from its thermodynamically stable siderophore complex is explored.
- 90Schalk, I. J.; Guillon, L. Fate of ferrisiderophores after import across bacterial outer membranes: different iron release strategies are observed in the cytoplasm or periplasm depending on the siderophore pathways. Amino Acids 2013, 44 (5), 1267– 1277, DOI: 10.1007/s00726-013-1468-2Google Scholar90https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXlvVCis7w%253D&md5=14a340b3a3a5fa9b8f9d775da504a4b1Fate of ferrisiderophores after import across bacterial outer membranes: different iron release strategies are observed in the cytoplasm or periplasm depending on the siderophore pathwaysSchalk, Isabelle J.; Guillon, LaurentAmino Acids (2013), 44 (5), 1267-1277CODEN: AACIE6; ISSN:0939-4451. (SpringerWienNewYork)A review. Siderophore prodn. and utilization is one of the major strategies deployed by bacteria to get access to iron, a key nutrient for bacterial growth. The biol. function of siderophores is to solubilize iron in the bacterial environment and to shuttle it back to the cytoplasm of the microorganisms. This uptake process for Gram-neg. species involves TonB-dependent transporters for translocation across the outer membranes. In Escherichia coli and many other Gram-neg. bacteria, ABC transporters assocd. with periplasmic binding proteins import ferrisiderophores across cytoplasmic membranes. Recent data reveal that in some siderophore pathways, this step can also be carried out by proton-motive force-dependent permeases, for example the ferrichrome and ferripyochelin pathways in Pseudomonas aeruginosa. Iron is then released from the siderophores in the bacterial cytoplasm by different enzymic mechanisms depending on the nature of the siderophore. Another strategy has been reported for the pyoverdine pathway in P. aeruginosa: iron is released from the siderophore in the periplasm and only siderophore-free iron is transported into the cytoplasm by an ABC transporter having two atypical periplasmic binding proteins. This review presents recent findings concerning both ferrisiderophore and siderophore-free iron transport across bacterial cytoplasmic membranes and considers current knowledge about the mechanisms involved in iron release from siderophores.
- 91Miethke, M.; Marahiel, M. A. Siderophore-Based Iron Acquisition and Pathogen Control. Microbiol. Mol. Biol. Rev. 2007, 71 (3), 413– 451, DOI: 10.1128/MMBR.00012-07Google Scholar91https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtFClu7jM&md5=70073a51cf331c919781a80bc403d780Siderophore-based iron acquisition and pathogen controlMiethke, Marcus; Marahiel, Mohamed A.Microbiology and Molecular Biology Reviews (2007), 71 (3), 413-451CODEN: MMBRF7; ISSN:1092-2172. (American Society for Microbiology)A review. High-affinity iron acquisition is mediated by siderophore-dependent pathways in the majority of pathogenic and nonpathogenic bacteria and fungi. Considerable progress has been made in characterizing and understanding mechanisms of siderophore synthesis, secretion, iron scavenging, and siderophore-delivered iron uptake and its release. The regulation of siderophore pathways reveals multilayer networks at the transcriptional and posttranscriptional levels. Due to the key role of many siderophores during virulence, coevolution led to sophisticated strategies of siderophore neutralization by mammals and (re)utilization by bacterial pathogens. Surprisingly, hosts also developed essential siderophore-based iron delivery and cell conversion pathways, which are of interest for diagnostic and therapeutic studies. In the last decades, natural and synthetic compds. have gained attention as potential therapeutics for iron-dependent treatment of infections and further diseases. Promising results for pathogen inhibition were obtained with various siderophore-antibiotic conjugates acting as "Trojan horse" toxins and siderophore pathway inhibitors. In this article, general aspects of siderophore-mediated iron acquisition, recent findings regarding iron-related pathogen-host interactions, and current strategies for iron-dependent pathogen control will be reviewed. Further concepts including the inhibition of novel siderophore pathway targets are discussed.
- 92Greenwood, K. T.; Luke, R. K. J. Enzymatic hydrolysis of enterochelin and its iron complex in Escherichia coli K-12. Properties of enterochelin esterase. Biochim. Biophys. Acta, Enzymol. 1978, 525 (1), 209– 218, DOI: 10.1016/0005-2744(78)90216-4Google ScholarThere is no corresponding record for this reference.
- 93Langman, L.; Young, I. G.; Frost, G. E.; Rosenberg, H.; Gibson, F. Enterochelin system of iron transport in Escherichia coli: mutations affecting ferric-enterochelin esterase. J. Bacteriol. 1972, 112 (3), 1142– 1149, DOI: 10.1128/jb.112.3.1142-1149.1972Google ScholarThere is no corresponding record for this reference.
- 94O’Brien, I. G.; Cox, G. B.; Gibson, F. Enterochelin hydrolysis and iron metabolism in Escherichia coli. Biochim. Biophys. Acta, Gen. Subj. 1971, 237 (3), 537– 549, DOI: 10.1016/0304-4165(71)90274-1Google ScholarThere is no corresponding record for this reference.
- 95Lin, H.; Fischbach, M. A.; Liu, D. R.; Walsh, C. T. In Vitro Characterization of Salmochelin and Enterobactin Trilactone Hydrolases IroD, IroE, and Fes. J. Am. Chem. Soc. 2005, 127 (31), 11075– 11084, DOI: 10.1021/ja0522027Google Scholar95https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmtVClsb0%253D&md5=8c32cf17a0a6a6a84848d76c890aa834In Vitro Characterization of Salmochelin and Enterobactin Trilactone Hydrolases IroD, IroE, and FesLin, Hening; Fischbach, Michael A.; Liu, David R.; Walsh, Christopher T.Journal of the American Chemical Society (2005), 127 (31), 11075-11084CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The iroA locus encodes five genes (iroB, iroC, iroD, iroE, iroN) that are found in pathogenic Salmonella and Escherichia coli strains. We recently reported that IroB is an enterobactin (Ent) C-glucosyltransferase, converting the siderophore into mono-, di-, and triglucosyl enterobactins (MGE, DGE, and TGE, resp.). Here, we report the characterization of IroD and IroE as esterases for the apo and Fe3+-bound forms of Ent, MGE, DGE, and TGE, and we compare their activities with those of Fes, the previously characterized enterobactin esterase. IroD hydrolyzes both apo and Fe3+-bound siderophores distributively to generate DHB-Ser and/or Glc-DHB-Ser, with higher catalytic efficiencies (kcat/Km) on Fe3+-bound forms, suggesting that IroD is the ferric MGE/DGE esterase responsible for cytoplasmic iron release. Similarly, Fes hydrolyzes ferric Ent more efficiently than apo Ent, confirming Fes is the ferric Ent esterase responsible for Fe3+ release from ferric Ent. Although each enzyme exhibits lower kcat's processing ferric siderophores, dramatic decreases in Km's for ferric siderophores result in increased catalytic efficiencies. The inability of Fes to efficiently hydrolyze ferric MGE, ferric DGE, or ferric TGE explains the requirement for IroD in the iroA cluster. IroE, in contrast, prefers apo siderophores as substrates and tends to hydrolyze the trilactone just once to produce linearized trimers. These data and the periplasmic location of IroE suggest that it hydrolyzes apo enterobactins while they are being exported. IroD hydrolyzes apo MGE (and DGE) regioselectively to give a single linear trimer product and a single linear dimer product as detd. by NMR.
- 96Miethke, M.; Klotz, O.; Linne, U.; May, J. J.; Beckering, C. L.; Marahiel, M. A. Ferri-bacillibactin uptake and hydrolysis in Bacillus subtilis. Mol. Microbiol. 2006, 61 (6), 1413– 1427, DOI: 10.1111/j.1365-2958.2006.05321.xGoogle ScholarThere is no corresponding record for this reference.
- 97Abergel, R. J.; Zawadzka, A. M.; Hoette, T. M.; Raymond, K. N. Enzymatic Hydrolysis of Trilactone Siderophores: Where Chiral Recognition Occurs in Enterobactin and Bacillibactin Iron Transport. J. Am. Chem. Soc. 2009, 131 (35), 12682– 12692, DOI: 10.1021/ja903051qGoogle Scholar97https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXps1yksr4%253D&md5=f33553eeb9bd456100451e708ce67e9aEnzymatic Hydrolysis of Trilactone Siderophores: Where Chiral Recognition Occurs in Enterobactin and Bacillibactin Iron TransportAbergel, Rebecca J.; Zawadzka, Anna M.; Hoette, Trisha M.; Raymond, Kenneth N.Journal of the American Chemical Society (2009), 131 (35), 12682-12692CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Bacillibactin and enterobactin are hexadentate catecholate siderophores produced by bacteria upon iron limitation to scavenge ferric ion and seem to be the ultimate siderophores of their two resp. domains: Gram-pos. and Gram-neg. Iron acquisition mediated by these trilactone-based ligands necessitates enzymic hydrolysis of the scaffold for successful intracellular iron delivery. The esterases BesA and Fes hydrolyze bacillibactin and enterobactin, resp., as well as the corresponding iron complexes. Bacillibactin binds iron through three 2,3-catecholamide moieties linked to a trithreonine scaffold via glycine spacers, whereas in enterobactin the iron-binding moieties are directly attached to a tri-L-serine backbone; although apparently minor, these structural differences result in markedly different iron coordination properties and iron transport behavior. Comparison of the soln. thermodn. and CD properties of bacillibactin, enterobactin and the synthetic analogs D-enterobactin, SERGlyCAM and D-SERGlyCAM has detd. the role of each different feature in the siderophores' mol. structures in ferric complex stability and metal chirality. While opposite metal chiralities in the different complexes did not affect transport and incorporation in Bacillus subtilis, ferric complexes formed with the various siderophores did not systematically promote growth of the bacteria. The bacillibactin esterase BesA is less specific than the enterobactin esterase Fes; BesA can hydrolyze the trilactones of both siderophores, while only the tri-L-serine trilactone is a substrate of Fes. Both enzymes are stereospecific and cannot cleave tri-D-serine lactones. These data provide a complete picture of the microbial iron transport mediated by these two siderophores, from initial recognition and transport to intracellular iron release.
- 98Ecker, F.; Haas, H.; Groll, M.; Huber, E. M. Iron Scavenging in Aspergillus Species: Structural and Biochemical Insights into Fungal Siderophore Esterases. Angew. Chem., Int. Ed. 2018, 57 (44), 14624– 14629, DOI: 10.1002/anie.201807093Google ScholarThere is no corresponding record for this reference.
- 99Gründlinger, M.; Gsaller, F.; Schrettl, M.; Lindner, H.; Haas, H. Aspergillus fumigatus SidJ mediates intracellular siderophore hydrolysis. Appl. Environ. Microbiol. 2013, 79 (23), 7534– 7536, DOI: 10.1128/AEM.01285-13Google ScholarThere is no corresponding record for this reference.
- 100Kragl, C.; Schrettl, M.; Abt, B.; Sarg, B.; Lindner, H. H.; Haas, H. EstB-mediated hydrolysis of the siderophore triacetylfusarinine C optimizes iron uptake of Aspergillus fumigatus. Eukaryotic Cell 2007, 6 (8), 1278– 1285, DOI: 10.1128/EC.00066-07Google ScholarThere is no corresponding record for this reference.
- 101Winkelmann, G.; Schmidtkunz, K.; Rainey, F. A. Characterization of a novel Spirillum-like bacterium that degrades ferrioxamine-type siderophores. BioMetals 1996, 9 (1), 78– 83, DOI: 10.1007/BF00188094Google ScholarThere is no corresponding record for this reference.
- 102Winkelmann, G.; Busch, B.; Hartmann, A.; Kirchhof, G.; Süssmuth, R.; Jung, G. Degradation of desferrioxamines by Azospirillum irakense: assignment of metabolites by HPLC/electrospray mass spectrometry. BioMetals 1999, 12 (3), 255– 264, DOI: 10.1023/A:1009242307134Google ScholarThere is no corresponding record for this reference.
- 103Pierwola, A.; Krupinski, T.; Zalupski, P.; Chiarelli, M.; Castignetti, D. Degradation Pathway and Generation of Monohydroxamic Acids from the Trihydroxamate Siderophore Deferrioxamine B. Appl. Environ. Microbiol. 2004, 70 (2), 831– 836, DOI: 10.1128/AEM.70.2.831-836.2004Google ScholarThere is no corresponding record for this reference.
- 104DeAngelis, R.; Forsyth, M.; Castignetti, D. The nutritional selectivity of a siderophore-catabolizing bacterium. BioMetals 1993, 6 (4), 234– 238, DOI: 10.1007/BF00187761Google ScholarThere is no corresponding record for this reference.
- 105Castignetti, D.; Siddiqui, A. S. The catabolism and heterotrophic nitrification of the siderophore deferrioxamine B. Biol. Met. 1990, 3 (3–4), 197– 203, DOI: 10.1007/BF01140579Google ScholarThere is no corresponding record for this reference.
- 106Sanchez, N.; Peterson, C. K.; Gonzalez, S. V.; Vadstein, O.; Olsen, Y.; Ardelan, M. V. Effect of hydroxamate and catecholate siderophores on iron availability in the diatom Skeletonema costatum: Implications of siderophore degradation by associated bacteria. Mar. Chem. 2019, 209, 107– 119, DOI: 10.1016/j.marchem.2019.01.005Google ScholarThere is no corresponding record for this reference.
- 107French, K. S.; Chukwuma, E.; Linshitz, I.; Namba, K.; Duckworth, O. W.; Cubeta, M. A.; Baars, O. Inactivation of siderophore iron-chelating moieties by the fungal wheat root symbiont Pyrenophora biseptata. Environ. Microbiol. Rep. 2024, 16 (1), e13234 DOI: 10.1111/1758-2229.13234Google ScholarThere is no corresponding record for this reference.
- 108Villavicencio, M.; Neilands, J. B. An inducible ferrichrome A-degrading peptidase from Pseudomonas FC-1. Biochemistry 1965, 4 (6), 1092– 1097, DOI: 10.1021/bi00882a017Google Scholar108https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF2MXktFyjt70%253D&md5=3680afaed7f51f32ab3e845e028841b4An inducible ferrichrome A-degrading peptidase from Pseudomonas FC-1Villavicencio, M.; Neilands, J. B.Biochemistry (1965), 4 (6), 1092-7CODEN: BICHAW; ISSN:0006-2960.Growth of Pseudomonas FC-1 on ferrichrome A or exposure of the cells to this cyclic peptide induced the formation of an alk. peptidase. Enzyme induction, which was inhibited by chloramphenicol, could not be obtained with general proteinaceous substrates such as peptone. The peptidase opens the ring of ferrichrome A at an acyl serine bond. The product, a linear hexapeptide, was isolated and characterized. An assay for the peptidase was developed, based on periodate oxidn. of the newly formed N-terminal serine residue, followed by detn. of H2CO via chromotropic acid. The enzyme, which is intracellular, was isolated in sol. form from ferrichrome A-grown cells by treatment of an acetone powder with snake venom in slightly alk. medium. A 40-fold purification was achieved by (NH4)2SO4 pptn. and gel filtration on Sephadex G-100. The purified enzyme was neither strongly activated nor inhibited by a series of bivalent metal ions; SH reagents did not destroy the activity. The pH optimum was about 9.0.
- 109Warren, R. A. J.; Neilands, J. B. Microbial degradation of the ferrichrome compounds. J. Gen. Microbiol. 1964, 35, 459– 470, DOI: 10.1099/00221287-35-3-459Google ScholarThere is no corresponding record for this reference.
- 110Warren, R. A.; Neilands, J. B. Mechanism of microbial catabolism of ferrichrome A. J. Biol. Chem. 1965, 240, 2055– 2058, DOI: 10.1016/S0021-9258(18)97424-7Google ScholarThere is no corresponding record for this reference.
- 111Hider, R. C.; Kong, X. Chemistry and biology of siderophores. Nat. Prod. Rep. 2010, 27 (5), 637– 657, DOI: 10.1039/b906679aGoogle Scholar111https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXls1Wrsb0%253D&md5=e4e2a8e10cc41de3d7f526b33802b4f7Chemistry and biology of siderophoresHider, Robert C.; Kong, Xiao-LeNatural Product Reports (2010), 27 (5), 637-657CODEN: NPRRDF; ISSN:0265-0568. (Royal Society of Chemistry)A review. Siderophores are compds. produced by bacteria, fungi and graminaceous plants for scavenging iron from the environment. They are low-mol.-wt. compds. (500-1500 daltons) possessing a high affinity for iron(iii) (Kf > 1030), the biosynthesis of which is regulated by iron levels and the function of which is to supply iron to the cell. This article briefly describes the classification and chem. properties of siderophores, before outlining research on siderophore biosynthesis and transport. Clin. important siderophores and the therapeutic potential of siderophore design are described. Appendix 1 provides a comprehensive list of siderophore structures.
- 112Kaipanchery, V.; Sharma, A.; Albericio, F.; de la Torre, B. G. Insights into the chemistry of the amphibactin–metal (M3+) interaction and its role in antibiotic resistance. Sci. Rep. 2020, 10 (1), 21049 DOI: 10.1038/s41598-020-77807-3Google ScholarThere is no corresponding record for this reference.
- 113Dhungana, S.; Crumbliss, A. L. Coordination Chemistry and Redox Processes in Siderophore-Mediated Iron Transport. Geomicrobiol. J. 2005, 22 (3–4), 87– 98, DOI: 10.1080/01490450590945870Google ScholarThere is no corresponding record for this reference.
- 114Gauglitz, J. M.; Iinishi, A.; Ito, Y.; Butler, A. Microbial Tailoring of Acyl Peptidic Siderophores. Biochemistry 2014, 53 (16), 2624– 2631, DOI: 10.1021/bi500266xGoogle Scholar114https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXmtFWksbw%253D&md5=f1a8bfec1d0d5c5e10373f7c68612494Microbial tailoring of acyl peptidic siderophoresGauglitz, Julia M.; Iinishi, Akira; Ito, Yusai; Butler, AlisonBiochemistry (2014), 53 (16), 2624-2631CODEN: BICHAW; ISSN:0006-2960. (American Chemical Society)Marine bacteria produce an abundance of suites of acylated siderophores characterized by a unique, species-dependent headgroup that binds iron(III) and one of a series of fatty acid appendages. Marinobacter sp. DS40M6 produces a suite of seven acylated marinobactins, with fatty acids ranging from satd. and unsatd. C12-C18 fatty acids. In the present study, the authors report that in the late log phase of growth, the fatty acids are hydrolyzed by an amide hydrolase producing the peptidic marinobactin headgroup. Halomonas aquamarina str. DS40M3, another marine bacterium isolated originally from the same sample of open ocean water as Marinobacter sp. DS40M6, produces the acyl aquachelins, also as a suite composed of a peptidic headgroup distinct from that of the marinobactins. In contrast to the acyl marinobactins, hydrolysis of the suite of acyl aquachelins is not detected, even when H. aquamarina str. DS40M3 is grown into the stationary phase. The Marinobacter cell-free ext. contg. the acyl amide hydrolase is active toward exogenous acyl-peptidic siderophores (e.g., aquachelin C, loihichelin C, as well as octanoyl homoserine lactone used in quorum sensing). Further, when H. aquamarina str. DS40M3 is cultured together with Marinobacter sp. DS40M6, the fatty acids of both suites of siderophores are hydrolyzed, and the aquachelin headgroup is also produced. Thus, the present study demonstrates that coculturing bacteria leads to metabolically tailored metabolites compared to growth in a single pure culture, which is interesting given the importance of siderophore-mediated iron acquisition for bacterial growth and that Marinobacter sp. DS40M6 and H. aquamarina str. DS40M3 were isolated from the same sample of seawater.
- 115Perraud, Q.; Moynié, L.; Gasser, V.; Munier, M.; Godet, J.; Hoegy, F.; Mély, Y.; Mislin, G. L. A.; Naismith, J. H.; Schalk, I. J. A Key Role for the Periplasmic PfeE Esterase in Iron Acquisition via the Siderophore Enterobactin in Pseudomonas aeruginosa. ACS Chem. Biol. 2018, 13 (9), 2603– 2614, DOI: 10.1021/acschembio.8b00543Google Scholar115https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsVCqtb%252FM&md5=7d511ea3d38706dd95cfa1d5a24daf5dA Key Role for the Periplasmic PfeE Esterase in Iron Acquisition via the Siderophore Enterobactin in Pseudomonas aeruginosaPerraud, Quentin; Moynie, Lucile; Gasser, Veronique; Munier, Mathilde; Godet, Julien; Hoegy, Francoise; Mely, Yves; Mislin, Gaetan. L. A.; Naismith, James H.; Schalk, Isabelle J.ACS Chemical Biology (2018), 13 (9), 2603-2614CODEN: ACBCCT; ISSN:1554-8929. (American Chemical Society)Enterobactin (ENT) is a siderophore (iron-chelating compd.) produced by Escherichia coli to gain access to iron, an indispensable nutrient for bacterial growth. ENT is used as an exosiderophore by Pseudomonas aeruginosa with transport of ferri-ENT across the outer membrane by the PfeA transporter. Next to the pfeA gene on the chromosome is localized a gene encoding for an esterase, PfeE, whose transcription is regulated, as for pfeA, by the presence of ENT in bacterial environment. Purified PfeE hydrolyzed ferri-ENT into three mols. of 2,3-DHBS (2,3-dihydroxybenzoylserine) still complexed with ferric iron, and complete dissocn. of iron from ENT chelating groups was only possible in the presence of both PfeE and an iron reducer, such as DTT. The crystal structure of PfeE and an inactive PfeE mutant complexed with ferri-ENT or a nonhydrolyzable ferri-catechol complex allowed identification of the enzyme binding site and the catalytic triad. Finally, cell fractionation and fluorescence microscopy showed periplasmic localization of PfeE in P. aeruginosa cells. Thus, the mol. mechanism of iron dissocn. from ENT in P. aeruginosa differs from that previously described in E. coli. In P. aeruginosa, siderophore hydrolysis occurs in the periplasm, with ENT never reaching the bacterial cytoplasm. In E. coli, ferri-ENT crosses the inner membrane via the ABC transporter FepBCD and ferri-ENT is hydrolyzed by the esterase Fes only once it is in the cytoplasm.
- 116Zeng, X.; Mo, Y.; Xu, F.; Lin, J. Identification and characterization of a periplasmic trilactone esterase, Cee, revealed unique features of ferric enterobactin acquisition in Campylobacter. Mol. Microbiol. 2013, 87 (3), 594– 608, DOI: 10.1111/mmi.12118Google ScholarThere is no corresponding record for this reference.
- 117Noinaj, N.; Guillier, M.; Barnard, T. J.; Buchanan, S. K. TonB-dependent transporters: regulation, structure, and function. Annu. Rev. Microbiol. 2010, 64, 43– 60, DOI: 10.1146/annurev.micro.112408.134247Google Scholar117https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsVeisL%252FO&md5=fa894bcacb012f9a74ada742cea84ea3TonB-dependent transporters: Regulation, structure, and functionNoinaj, Nicholas; Guillier, Maude; Barnard, Travis J.; Buchanan, Susan K.Annual Review of Microbiology (2010), 64 (), 43-60CODEN: ARMIAZ; ISSN:0066-4227. (Annual Reviews Inc.)A review. TonB-dependent transporters (TBDTs) are bacterial outer membrane proteins that bind and transport ferric chelates, called siderophores, as well as vitamin B12, nickel complexes, and carbohydrates. The transport process requires energy in the form of proton motive force and a complex of three inner membrane proteins, TonB-ExbB-ExbD, to transduce this energy to the outer membrane. The siderophore substrates range in complexity from simple small mols. such as citrate to large proteins such as serum transferrin and Hb. Because iron uptake is vital for almost all bacteria, expression of TBDTs is regulated in a no. of ways that include metal-dependent regulators, σ/anti-σ factor systems, small RNAs, and even a riboswitch. In recent years, many new structures of TBDTs have been solved in various states, resulting in a more complete understanding of siderophore selectivity and binding, signal transduction across the outer membrane, and interaction with the TonB-ExbB-ExbD complex. However, the transport mechanism is still unclear. In this review, the authors summarize recent progress in understanding regulation, structure, and function in TBDTs and questions remaining to be answered.
- 118Rivera, M. Bacterioferritin: Structure, Dynamics, and Protein–Protein Interactions at Play in Iron Storage and Mobilization. Acc. Chem. Res. 2017, 50 (2), 331– 340, DOI: 10.1021/acs.accounts.6b00514Google ScholarThere is no corresponding record for this reference.
- 119Kramer, J.; Özkaya, Ö.; Kümmerli, R. Bacterial siderophores in community and host interactions. Nat. Rev. Microbiol. 2020, 18 (3), 152– 163, DOI: 10.1038/s41579-019-0284-4Google Scholar119https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitF2qt7bP&md5=e1ab70ab7a7effab401a6a792ad6320eBacterial siderophores in community and host interactionsKramer, Jos; Ozkaya, Ozhan; Kummerli, RolfNature Reviews Microbiology (2020), 18 (3), 152-163CODEN: NRMACK; ISSN:1740-1526. (Nature Research)Iron is an essential trace element for most organisms. A common way for bacteria to acquire this nutrient is through the secretion of siderophores, which are secondary metabolites that scavenge iron from environmental stocks and deliver it to cells via specific receptors. While there has been tremendous interest in understanding the mol. basis of siderophore synthesis, uptake and regulation, questions about the ecol. and evolutionary consequences of siderophore secretion have only recently received increasing attention. In this Review, we outline how eco-evolutionary questions can complement the mechanistic perspective and help to obtain a more integrated view of siderophores. In particular, we explain how secreted diffusible siderophores can affect other community members, leading to cooperative, exploitative and competitive interactions between individuals. These social interactions in turn can spur co-evolutionary arms races between strains and species, lead to ecol. dependencies between them and potentially contribute to the formation of stable communities. In brief, this Review shows that siderophores are much more than just iron carriers: they are important mediators of interactions between members of microbial assemblies and the eukaryotic hosts they inhabit.
- 120Barber, M. F.; Elde, N. C. Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy. Trends Genet. 2015, 31 (11), 627– 636, DOI: 10.1016/j.tig.2015.09.001Google Scholar120https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFCrurfE&md5=5b688bdf399f88dc883a3a09866afb53Buried Treasure: Evolutionary Perspectives on Microbial Iron PiracyBarber, Matthew F.; Elde, Nels C.Trends in Genetics (2015), 31 (11), 627-636CODEN: TRGEE2; ISSN:0168-9525. (Elsevier Ltd.)A review. Host-pathogen interactions provide valuable systems for the study of evolutionary genetics and natural selection. The sequestration of essential iron has emerged as a crucial innate defense system termed nutritional immunity, leading pathogens to evolve mechanisms of iron piracy to scavenge this metal from host proteins. This battle for iron carries numerous consequences not only for host-pathogen evolution but also microbial community interactions. Here the authors highlight recent and potential future areas of study on the evolutionary implications of microbial iron piracy in relation to mol. arms races, host range, competition, and virulence. Applying evolutionary genetic approaches to the study of microbial iron acquisition could also provide new inroads for understanding and combating infectious disease.
- 121Gauglitz, J. M.; Boiteau, R. M.; McLean, C.; Babcock-Adams, L.; McIlvin, M. R.; Moran, D. M.; Repeta, D. J.; Saito, M. A. Dynamic proteome response of a marine Vibrio to a gradient of iron and ferrioxamine bioavailability. Mar. Chem. 2021, 229, 103913 DOI: 10.1016/j.marchem.2020.103913Google ScholarThere is no corresponding record for this reference.
- 122Thode, S. K.; Rojek, E.; Kozlowski, M.; Ahmad, R.; Haugen, P. Distribution of siderophore gene systems on a Vibrionaceae phylogeny: Database searches, phylogenetic analyses and evolutionary perspectives. PLoS One 2018, 13 (2), e0191860 DOI: 10.1371/journal.pone.0191860Google ScholarThere is no corresponding record for this reference.
- 123Eickhoff, M. J.; Bassler, B. L. Vibrio fischeri siderophore production drives competitive exclusion during dual-species growth. Mol. Microbiol. 2020, 114 (2), 244– 261, DOI: 10.1111/mmi.14509Google ScholarThere is no corresponding record for this reference.
- 124González, J. M.; Mayer, F.; Moran, M. A.; Hodson, R. E.; Whitman, W. B. Microbulbifer hydrolyticus gen. nov., sp. nov., and Marinobacterium georgiense gen. nov., sp. nov., Two Marine Bacteria from a Lignin-Rich Pulp Mill Waste Enrichment Community. Int. J. Syst. Bacteriol. 1997, 47 (2), 369– 376, DOI: 10.1099/00207713-47-2-369Google ScholarThere is no corresponding record for this reference.
- 125Williamson, N. R.; Fineran, P. C.; Gristwood, T.; Chawrai, S. R.; Leeper, F. J.; Salmond, G. P. Anticancer and immunosuppressive properties of bacterial prodiginines. Future Microbiol. 2007, 2 (6), 605– 618, DOI: 10.2217/17460913.2.6.605Google ScholarThere is no corresponding record for this reference.
- 126Nguyen, S. L. T.; Nguyen, T. C.; Do, T. T.; Vu, T. L.; Nguyen, T. T.; Do, T. T.; Nguyen, T. H. T.; Le, T. H.; Trinh, D. K.; Nguyen, T. A. T. Study on the Anticancer Activity of Prodigiosin from Variants of Serratia Marcescens QBN VTCC 910026. BioMed Res. Int. 2022, 2022 (1), 4053074 DOI: 10.1155/2022/4053074Google ScholarThere is no corresponding record for this reference.
- 127Danevčič, T.; Borić Vezjak, M.; Zorec, M.; Stopar, D. Prodigiosin - A Multifaceted Escherichia coli Antimicrobial Agent. PLoS One 2016, 11 (9), e0162412 DOI: 10.1371/journal.pone.0162412Google ScholarThere is no corresponding record for this reference.
- 128Arivuselvam, R.; Dera, A. A.; Parween Ali, S.; Alraey, Y.; Saif, A.; Hani, U.; Ramakrishnan, S. A.; Azeeze, M.; Rajeshkumar, R.; Susil, A.; Harindranath, H.; Kumar, B. R. P. Isolation, Identification, and Antibacterial Properties of Prodigiosin, a Bioactive Product Produced by a New Serratia marcescens JSSCPM1 Strain: Exploring the Biosynthetic Gene Clusters of Serratia Species for Biological Applications. Antibiotics 2023, 12 (9), 1466 DOI: 10.3390/antibiotics12091466Google ScholarThere is no corresponding record for this reference.
- 129Kim, H. J.; Lee, M.-S.; Jeong, S. K.; Lee, S. J. Transcriptomic analysis of the antimicrobial activity of prodigiosin against Cutibacterium acnes. Sci. Rep. 2023, 13 (1), 17412 DOI: 10.1038/s41598-023-44612-7Google ScholarThere is no corresponding record for this reference.
- 130Zhang, H.; Peng, Y.; Zhang, S.; Cai, G.; Li, Y.; Yang, X.; Yang, K.; Chen, Z.; Zhang, J.; Wang, H.; Zheng, T.; Zheng, W. Algicidal Effects of Prodigiosin on the Harmful Algae Phaeocystis globosa. Front. Microbiol. 2016, 7, 602 DOI: 10.3389/fmicb.2016.00602Google ScholarThere is no corresponding record for this reference.
- 131Yang, K.; Chen, Q.; Zhang, D.; Zhang, H.; Lei, X.; Chen, Z.; Li, Y.; Hong, Y.; Ma, X.; Zheng, W.; Tian, Y.; Zheng, T.; Xu, H. The algicidal mechanism of prodigiosin from Hahella sp. KA22 against Microcystis aeruginosa. Sci. Rep. 2017, 7 (1), 7750 DOI: 10.1038/s41598-017-08132-5Google ScholarThere is no corresponding record for this reference.
- 132Gomez Valdez, L.; Rondan Dueñas, J. C.; Andrade, A. J.; Del Valle, E. E.; Doucet, M. E.; Lax, P. In vitro and in vivo nematicidal activity of prodigiosin against the plant-parasitic nematode Nacobbus celatus. Biocontrol Sci. Technol. 2022, 32 (6), 741– 751, DOI: 10.1080/09583157.2022.2045474Google ScholarThere is no corresponding record for this reference.
- 133Longeon, A.; Copp, B. R.; Quévrain, E.; Roué, M.; Kientz, B.; Cresteil, T.; Petek, S.; Debitus, C.; Bourguet-Kondracki, M.-L. Bioactive Indole Derivatives from the South Pacific Marine Sponges Rhopaloeides odorabile and Hyrtios sp. Mar. Drugs 2011, 9 (5), 879– 888, DOI: 10.3390/md9050879Google ScholarThere is no corresponding record for this reference.
- 134Miguel-Gordo, M.; Gegunde, S.; Calabro, K.; Jennings, L. K.; Alfonso, A.; Genta-Jouve, G.; Vacelet, J.; Botana, L. M.; Thomas, O. P. Bromotryptamine and Bromotyramine Derivatives from the Tropical Southwestern Pacific Sponge Narrabeena nigra. Mar. Drugs 2019, 17 (6), 319 DOI: 10.3390/md17060319Google ScholarThere is no corresponding record for this reference.
- 135Peters, L.; König, G. M.; Terlau, H.; Wright, A. D. Four New Bromotryptamine Derivatives from the Marine Bryozoan Flustra foliacea. J. Nat. Prod. 2002, 65 (11), 1633– 1637, DOI: 10.1021/np0105984Google Scholar135https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XmvVGnt7k%253D&md5=e7ae9af1dbb3480de82de1035e601958Four new bromotryptamine derivatives from the marine bryozoan Flustra foliaceaPeters, Lars; Koenig, Gabriele M.; Terlau, Heinrich; Wright, Anthony D.Journal of Natural Products (2002), 65 (11), 1633-1637CODEN: JNPRDF; ISSN:0163-3864. (American Chemical Society)Ten brominated alkaloids, 6-bromo-2-(1,1-dimethyl-2-propenyl)-1H-indole-3-carbaldehyde (I), N-(2-[6-bromo-2-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]ethyl)-N-methylmethanesulfonamide (II), deformylflustrabromine (III), flustrabromine (IV), (3aR*,8aR*)-6-bromo-3a-[(2E)-3,7-dimethyl-2,6-octadienyl]-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-7-ol (V), flustramine C (VI), dihydroflustramine C (VII), flustramine A (VIII), flustramine D, and flustraminol A, and the diterpene 4,6-bis(4-methylpent-3-en-1-yl)-6-methylcyclohexa-1,3-diene-carbaldehyde were isolated from the dichloromethane ext. of the North Sea bryozoan Flustra foliacea. Of the 10, four (I-III and V) represent new natural products. The structures of all isolates were elucidated by interpretation of their spectroscopic data (NMR, MS, UV, and IR). For compd. IV complete 13C NMR data are reported for the first time. Compds. III and VI-VIII were tested on voltage-activated potassium and sodium channels. Flustramine A shows an unspecific blocking activity on Kv1.4 potassium-mediated currents.
- 136Di, X.; Wang, S.; Oskarsson, J. T.; Rouger, C.; Tasdemir, D.; Hardardottir, I.; Freysdottir, J.; Wang, X.; Molinski, T. F.; Omarsdottir, S. Bromotryptamine and Imidazole Alkaloids with Anti-inflammatory Activity from the Bryozoan Flustra foliacea. J. Nat. Prod. 2020, 83 (10), 2854– 2866, DOI: 10.1021/acs.jnatprod.0c00126Google Scholar136https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvFOmsLnL&md5=168cdc55e3ac5958d768e7f65c1b92caBromotryptamine and Imidazole Alkaloids with Anti-inflammatory Activity from the Bryozoan Flustra foliaceaDi, Xiaxia; Wang, Shuqi; Oskarsson, Jon T.; Rouger, Caroline; Tasdemir, Deniz; Hardardottir, Ingibjorg; Freysdottir, Jona; Wang, Xiao; Molinski, Tadeusz F.; Omarsdottir, SesseljaJournal of Natural Products (2020), 83 (10), 2854-2866CODEN: JNPRDF; ISSN:0163-3864. (American Chemical Society-American Society of Pharmacognosy)Chem. investigation of the marine bryozoan Flustra foliacea collected in Iceland resulted in isolation of 13 new bromotryptamine alkaloids, flustramines Q-W and flustraminols C-H, and 2 new imidazole alkaloids, flustrimidazoles A and B, together with 12 previously described compds. Their structures were established by detailed spectroscopic anal. using 1D and 2D NMR and HRESIMS. The structure of flustramine R was verified by calcns. of the 13C and 1H NMR chem. shifts using d. functional theory. The relative and abs. configurations of the new compds. were elucidated on the basis of coupling const. anal., NOESY, [α]D, and ECD spectroscopic data, in addn. to chem. derivatization. The compds. were tested for in vitro anti-inflammatory activity using a dendritic cell model. Eight compds. decreased dendritic cell secretion of the pro-inflammatory cytokine IL-12p40, and 2 compds. increased secretion of the anti-inflammatory cytokine IL-10. Deformylflustrabromine B showed the most potent anti-inflammatory effect (IC50 2.9 μM). These results demonstrate that F. foliacea from Iceland expresses a broad range of brominated alkaloids, many without structural precedents. The potent anti-inflammatory activity in vitro of deformylflustrabromine B warrants further investigations into its potential as a lead for inflammation-related diseases.
- 137Simmons, T. L.; Coates, R. C.; Clark, B. R.; Engene, N.; Gonzalez, D.; Esquenazi, E.; Dorrestein, P. C.; Gerwick, W. H. Biosynthetic origin of natural products isolated from marine microorganism–invertebrate assemblages. Proc. Natl. Acad. Sci. U.S.A. 2008, 105 (12), 4587– 4594, DOI: 10.1073/pnas.0709851105Google ScholarThere is no corresponding record for this reference.
- 138Ding, L.; He, S.; Wu, W.; Jin, H.; Zhu, P.; Zhang, J.; Wang, T.; Yuan, Y.; Yan, X. Discovery and Structure-Based Optimization of 6-Bromotryptamine Derivatives as Potential 5-HT2A Receptor Antagonists. Molecules 2015, 20 (9), 17675– 17683, DOI: 10.3390/molecules200917675Google ScholarThere is no corresponding record for this reference.
- 139Diep, C. N.; Lyakhova, E. G.; Berdyshev, D. V.; Kalinovsky, A. I.; Tu, V. A.; Cuong, N. X.; Nam, N. H.; Minh, C. V.; Stonik, V. A. Structures and absolute stereochemistry of guaiane sesquiterpenoids from the gorgonian Menella woodin. Tetrahedron Lett. 2015, 56 (50), 7001– 7004, DOI: 10.1016/j.tetlet.2015.10.102Google ScholarThere is no corresponding record for this reference.
- 140Phan, C.-S.; Kamada, T.; Ishii, T.; Hamada, T.; Vairappan, C. S. A New Guaiane-type Sesquiterpenoid from a Bornean Soft Coral, Xenia stellifera. Nat. Prod. Commun. 2018, 13, 1934578X1801300105 DOI: 10.1177/1934578x1801300105Google ScholarThere is no corresponding record for this reference.
- 141Kozawa, S.; Ishiyama, H.; Fromont, J.; Kobayashi, J. Halichonadin E, a Dimeric Sesquiterpenoid from the Sponge Halichondria sp. J. Nat. Prod. 2008, 71 (3), 445– 447, DOI: 10.1021/np0703139Google Scholar141https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtlOhu7nK&md5=344532936687a8f37493c7f52ebf936cHalichonadin E, a Dimeric Sesquiterpenoid from the Sponge Halichondria sp.Kozawa, Shingo; Ishiyama, Haruaki; Fromont, Jane; Kobayashi, Jun'ichiJournal of Natural Products (2008), 71 (3), 445-447CODEN: JNPRDF; ISSN:0163-3864. (American Chemical Society-American Society of Pharmacognosy)A new dimeric sesquiterpenoid with eudesmane and aromadendrane skeletons linked through a urea fragment, halichonadin E (I), was isolated from a marine sponge Halichondria sp., and the gross structure and relative configuration of I were elucidated on the basis of spectroscopic data. Halichonadin E is the first hetero-dimeric sesquiterpenoid with eudesmane and aromadendrane skeletons linked through a urea fragment.
- 142Drew, D. P.; Krichau, N.; Reichwald, K.; Simonsen, H. T. Guaianolides in apiaceae: perspectives on pharmacology and biosynthesis. Phytochem. Rev. 2009, 8 (3), 581– 599, DOI: 10.1007/s11101-009-9130-zGoogle ScholarThere is no corresponding record for this reference.
- 143Li, X.-W.; Weng, L.; Gao, X.; Zhao, Y.; Pang, F.; Liu, J.-H.; Zhang, H.-F.; Hu, J.-F. Antiproliferative and apoptotic sesquiterpene lactones from Carpesium faberi. Bioorg. Med. Chem. Lett. 2011, 21 (1), 366– 372, DOI: 10.1016/j.bmcl.2010.10.138Google ScholarThere is no corresponding record for this reference.
- 144Wang, S.; Sun, J.; Zeng, K.; Chen, X.; Zhou, W.; Zhang, C.; Jin, H.; Jiang, Y.; Tu, P. Sesquiterpenes from Artemisia argyi: Absolute Configurations and Biological Activities. Eur. J. Org. Chem. 2014, 2014 (5), 973– 983, DOI: 10.1002/ejoc.201301445Google ScholarThere is no corresponding record for this reference.
- 145Yuuya, S.; Hagiwara, H.; Suzuki, T.; Ando, M.; Yamada, A.; Suda, K.; Kataoka, T.; Nagai, K. Guaianolides as immunomodulators. Synthesis and biological activities of dehydrocostus lactone, mokko lactone, eremanthin, and their derivatives. J. Nat. Prod. 1999, 62 (1), 22– 30, DOI: 10.1021/np980092uGoogle Scholar145https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXns1ylsr8%253D&md5=8f3c277e050eeba0fcc6e0a09bb7182eGuaianolides as Immunomodulators. Synthesis and Biological Activities of Dehydrocostus Lactone, Mokko Lactone, Eremanthin, and Their DerivativesYuuya, Saori; Hagiwara, Hisahiro; Suzuki, Toshio; Ando, Masayoshi; Yamada, Atsushi; Suda, Kouji; Kataoka, Takao; Nagai, KazuoJournal of Natural Products (1999), 62 (1), 22-30CODEN: JNPRDF; ISSN:0163-3864. (American Chemical Society)The naturally occurring guaianolides, namely mokko lactone (I; R1 = H, R2 = Me), dehydrocostus lactone (I; R1R2 = CH2), eremanthin (II), and related guaianolides, e.g. III, IV, V and VI, have been synthesized starting from l-α-santonin in an effort to examine their structure-activity relationship as inhibitors of the killing function of cytotoxic T lymphocytes (CTL) and the induction of intercellular adhesion mol.-1 (ICAM-1). It was obsd. during the present study that the guaianolides possessing an α-methylene γ-lactone moiety, i.e., I (R1R2 = CH2), II, III, IV, V, and VI, exhibited significant inhibitory activity toward the killing function of CTL and the induction of ICAM-1.
- 146De Toledo, J. S.; Ambrósio, S. R.; Borges, C. H. G.; Manfrim, V.; Cerri, D. G.; Cruz, A. K.; Da Costa, F. B. In Vitro Leishmanicidal Activities of Sesquiterpene Lactones from Tithonia diversifolia against Leishmania braziliensis Promastigotes and Amastigotes. Molecules 2014, 19 (5), 6070– 6079, DOI: 10.3390/molecules19056070Google ScholarThere is no corresponding record for this reference.
- 147Niu, S.; Xie, C.-L.; Xia, J.-M.; Luo, Z.-H.; Shao, Z.; Yang, X.-W. New anti-inflammatory guaianes from the Atlantic hydrotherm-derived fungus Graphostroma sp. MCCC 3A00421. Sci. Rep. 2018, 8 (1), 530 DOI: 10.1038/s41598-017-18841-6Google ScholarThere is no corresponding record for this reference.
- 148Chakraborty, K.; Lipton, A. P.; Paulraj, R.; Chakraborty, R. D. Guaiane sesquiterpenes from seaweed Ulva fasciata Delile and their antibacterial properties. Eur. J. Med. Chem. 2010, 45 (6), 2237– 2244, DOI: 10.1016/j.ejmech.2010.01.065Google ScholarThere is no corresponding record for this reference.
- 149Zhou, L.; Chen, B.; Zhang, Y.; Zhang, X.; Li, X.; Wang, C. New Anti-HSV-1 Guaiane Lactone from Hainan Gorgonian Echinomuricea indomalaccensis. J. Ocean Univ. China 2022, 21 (4), 965– 968, DOI: 10.1007/s11802-022-4878-yGoogle ScholarThere is no corresponding record for this reference.
- 150Battista, N.; Bari, M.; Bisogno, T. N-Acyl Amino Acids: Metabolism, Molecular Targets, and Role in Biological Processes. Biomolecules 2019, 9 (12), 822 DOI: 10.3390/biom9120822Google Scholar150https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVWgt70%253D&md5=a340c5acb9b4c9dbfe9b0d0762287b8bN-acyl amino acids: metabolism, molecular targets, and role in biological processesBattista, Natalia; Bari, Monica; Bisogno, TizianaBiomolecules (2019), 9 (12), 822CODEN: BIOMHC; ISSN:2218-273X. (MDPI AG)A review. The lipid signal is becoming increasingly crowded as increasingly fatty acid amide derivs. are being identified and considered relevant therapeutic targets. The identification of N-arachidonoyl-ethanolamine as endogenous ligand of cannabinoid type-1 and type-2 receptors as well as the development of different -omics technologies have the merit to have led to the discovery of a huge no. of naturally occurring N-acyl-amines. Among those mediators, N-acyl amino acids, chem. related to the endocannabinoids and belonging to the complex lipid signaling system now known as endocannabinoidome, have been rapidly growing for their therapeutic potential. Here, we review the current knowledge of the mechanisms for the biosynthesis and inactivation of the N-acyl amino acids, as well as the various mol. targets for some of the N-acyl amino acids described so far.
- 151Burstein, S. The elmiric acids: Biologically active anandamide analogs. Neuropharmacology 2008, 55 (8), 1259– 1264, DOI: 10.1016/j.neuropharm.2007.11.011Google ScholarThere is no corresponding record for this reference.
- 152Cani, P. D.; Plovier, H.; Van Hul, M.; Geurts, L.; Delzenne, N. M.; Druart, C.; Everard, A. Endocannabinoids ─ at the crossroads between the gut microbiota and host metabolism. Nat. Rev. Endocrinol. 2016, 12 (3), 133– 143, DOI: 10.1038/nrendo.2015.211Google ScholarThere is no corresponding record for this reference.
- 153Pacher, P.; Kunos, G. Modulating the endocannabinoid system in human health and disease – successes and failures. FEBS J. 2013, 280 (9), 1918– 1943, DOI: 10.1111/febs.12260Google ScholarThere is no corresponding record for this reference.
- 154Arul Prakash, S.; Kamlekar, R. K. Function and therapeutic potential of N-acyl amino acids. Chem. Phys. Lipids 2021, 239, 105114 DOI: 10.1016/j.chemphyslip.2021.105114Google ScholarThere is no corresponding record for this reference.
- 155Miyazaki, Y.; Oka, S.; Hara-Hotta, H.; Yano, I. Stimulation and inhibition of polymorphonuclear leukocytes phagocytosis by lipoamino acids isolated from Serratia marcescens. FEMS Immunol. Med. Microbiol. 1993, 6 (4), 265– 271, DOI: 10.1111/j.1574-695X.1993.tb00338.xGoogle ScholarThere is no corresponding record for this reference.
- 156Cho, W.; York, A. G.; Wang, R.; Wyche, T. P.; Piizzi, G.; Flavell, R. A.; Crawford, J. M. N-Acyl Amides from Neisseria meningitidis and Their Role in Sphingosine Receptor Signaling. Chembiochem 2022, 23 (22), e202200490 DOI: 10.1002/cbic.202200490Google ScholarThere is no corresponding record for this reference.
- 157Cohen, L. J.; Esterhazy, D.; Kim, S.-H.; Lemetre, C.; Aguilar, R. R.; Gordon, E. A.; Pickard, A. J.; Cross, J. R.; Emiliano, A. B.; Han, S. M.; Chu, J.; Vila-Farres, X.; Kaplitt, J.; Rogoz, A.; Calle, P. Y.; Hunter, C.; Bitok, J. K.; Brady, S. F. Commensal bacteria make GPCR ligands that mimic human signalling molecules. Nature 2017, 549 (7670), 48– 53, DOI: 10.1038/nature23874Google Scholar157https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsVWhu7vF&md5=a0fdeb4b2d2bbfd62542e4daba87822dCommensal bacteria make GPCR ligands that mimic human signalling moleculesCohen, Louis J.; Esterhazy, Daria; Kim, Seong-Hwan; Lemetre, Christophe; Aguilar, Rhiannon R.; Gordon, Emma A.; Pickard, Amanda J.; Cross, Justin R.; Emiliano, Ana B.; Han, Sun M.; Chu, John; Vila-Farres, Xavier; Kaplitt, Jeremy; Rogoz, Aneta; Calle, Paula Y.; Hunter, Craig; Bitok, J. Kipchirchir; Brady, Sean F.Nature (London, United Kingdom) (2017), 549 (7670), 48-53CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Commensal bacteria are believed to have important roles in human health. The mechanisms by which they affect mammalian physiol. remain poorly understood, but bacterial metabolites are likely to be key components of host interactions. Here we use bioinformatics and synthetic biol. to mine the human microbiota for N-acyl amides that interact with G-protein-coupled receptors (GPCRs). We found that N-acyl amide synthase genes are enriched in gastrointestinal bacteria and the lipids that they encode interact with GPCRs that regulate gastrointestinal tract physiol. Mouse and cell-based models demonstrate that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands, although future studies are needed to define their potential physiol. role in humans. Our results suggest that chem. mimicry of eukaryotic signaling mols. may be common among commensal bacteria and that manipulation of microbiota genes encoding metabolites that elicit host cellular responses represents a possible small-mol. therapeutic modality (microbiome-biosynthetic gene therapy).
- 158Brady, S. F.; Chao, C. J.; Clardy, J. New Natural Product Families from an Environmental DNA (eDNA) Gene Cluster. J. Am. Chem. Soc. 2002, 124 (34), 9968– 9969, DOI: 10.1021/ja0268985Google Scholar158https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XlslKjsb8%253D&md5=e67210cb279b3df95d96814ed5460bcbNew natural product families from an environmental DNA (eDNA) gene clusterBrady, Sean F.; Chao, Carol J.; Clardy, JonJournal of the American Chemical Society (2002), 124 (34), 9968-9969CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Uncultured bacteria represent a potentially rich source of new and useful natural products. Studying these natural products requires the development of effective yet straightforward methods to access the small-mol. chem. diversity produced by uncultured bacteria. In this study, DNA extd. directly from soil samples (environmental DNA, eDNA) was used to construct cosmid libraries in Escherichia coli, and these clones were then assayed for the prodn. of antibiosis. A 13 open reading frame (ORF) biosynthetic gene cluster (feeA-M) found in one of the antibacterial active clones, CSLC-2, confers to E. coli the prodn. of two new families of natural products that are derived from long chain N-acyltyrosines. The fee gene cluster and three families of the long chain acyl phenols derived from tyrosine (families 1, 2, and 3) are described.
- 159Brady, S. F.; Clardy, J. Long-Chain N-Acyl Amino Acid Antibiotics Isolated from Heterologously Expressed Environmental DNA. J. Am. Chem. Soc. 2000, 122 (51), 12903– 12904, DOI: 10.1021/ja002990uGoogle Scholar159https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXptVClsbg%253D&md5=7ce546caf1f69af61224060174f90e3bLong-Chain N-Acyl Amino Acid Antibiotics Isolated from Heterologously Expressed Environmental DNABrady, Sean F.; Clardy, JonJournal of the American Chemical Society (2000), 122 (51), 12903-12904CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The authors report the characterization of new natural products which are a series of long-chain N-acyl-L-tyrosine antibiotics and the gene for a long-chain N-acyl amino acid synthase. A cosmid library of DNA extd. from soil samples (eDNA) was screened for prodn. of antibacterial activity using a plate assay. A clone which produced an org. ext. with antibacterial activity was further characterized by insertion mutagenesis and sequence anal. The antibacterial activity was assocd. with an open reading frame ORF1 which encodes a predicted N-acyl transferase. The active org. ext. produced by subclone CLS12.1 was purified and analyzed by mass spectroscopy and ninhydrin assay and consisted of a series of long-chain satd. and unsatd. acyl deriv. of tyrosine named CSL12-A through CSL12-M. CSL12-A through CSL12-M varied in antibacterial activity. Activity and structure of the most abundant (CSL12-C, N-decanoyl-L-tyrosine), and one of the most active (CSL12-G, N-myristoyl-L-tyrosine) were confirmed by total synthesis.
- 160Brady, S. F.; Chao, C. J.; Clardy, J. Long-chain N-acyltyrosine synthases from environmental DNA. Appl. Environ. Microbiol. 2004, 70 (11), 6865– 6870, DOI: 10.1128/AEM.70.11.6865-6870.2004Google ScholarThere is no corresponding record for this reference.
- 161Peypoux, F.; Laprévote, O.; Pagadoy, M.; Wallach, J. N-Acyl derivatives of Asn, new bacterial N-acyl D-amino acids with surfactant activity. Amino Acids 2004, 26 (2), 209– 214, DOI: 10.1007/s00726-003-0056-2Google ScholarThere is no corresponding record for this reference.
- 162Geiger, O.; González-Silva, N.; López-Lara, I. M.; Sohlenkamp, C. Amino acid-containing membrane lipids in bacteria. Prog. Lipid Res. 2010, 49 (1), 46– 60, DOI: 10.1016/j.plipres.2009.08.002Google Scholar162https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhsFykt7vJ&md5=bebdaea080253a8e5d25d63f9cac663cAmino acid-containing membrane lipids in bacteriaGeiger, Otto; Gonzalez-Silva, Napoleon; Lopez-Lara, Isabel M.; Sohlenkamp, ChristianProgress in Lipid Research (2010), 49 (1), 46-60CODEN: PLIRDW; ISSN:0163-7827. (Elsevier Ltd.)A review. In the bacterial model organism Escherichia coli only the three major membrane lipids phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin occur, all of which belong to the glycerophospholipids. The amino acid-contg. phosphatidylserine is a major lipid in eukaryotic membranes but in most bacteria it occurs only as a minor biosynthetic intermediate. In some bacteria, the anionic glycerophospholipids phosphatidylglycerol and cardiolipin can be decorated with aminoacyl residues. For example, phosphatidylglycerol can be decorated with lysine, alanine, or arginine whereas in the case of cardiolipin, lysine or -alanine modifications are known. In few bacteria, diacylglycerol-derived lipids can be substituted with lysine or homoserine. Acyl-oxyacyl lipids in which the lipidic part is amide-linked to the α-amino group of an amino acid are widely distributed among bacteria and ornithine-contg. lipids are the most common version of this lipid type. Only few bacterial groups form glycine-contg. lipids, serineglycine-contg. lipids, sphingolipids, or sulfonolipids. Although many of these amino acid-contg. bacterial membrane lipids are produced in response to certain stress conditions, little is known about the specific mol. functions of these lipids.
- 163Yagi, H.; Corzo, G.; Nakahara, T. N-acyl amino acid biosynthesis in marine bacterium, Deleya marina. Biochim. Biophys. Acta, Gen. Subj. 1997, 1336 (1), 28– 32, DOI: 10.1016/S0304-4165(97)00009-3Google ScholarThere is no corresponding record for this reference.
- 164Craig, J. W.; Cherry, M. A.; Brady, S. F. Long-chain N-acyl amino acid synthases are linked to the putative PEP-CTERM/exosortase protein-sorting system in Gram-negative bacteria. J. Bacteriol. 2011, 193 (20), 5707– 5715, DOI: 10.1128/JB.05426-11Google ScholarThere is no corresponding record for this reference.
- 165Little, A. E. F.; Robinson, C. J.; Peterson, S. B.; Raffa, K. F.; Handelsman, J. Rules of Engagement: Interspecies Interactions that Regulate Microbial Communities. Annu. Rev. Microbiol. 2008, 62, 375– 401, DOI: 10.1146/annurev.micro.030608.101423Google Scholar165https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXht1Gls73K&md5=58ba8b32a71f62f37b61e19f1b537b6aRules of engagement: interspecies interactions that regulate microbial communitiesLittle, Ainslie E. F.; Robinson, Courtney J.; Peterson, S. Brook; Raffa, Kenneth F.; Handelsman, JoAnnual Review of Microbiology (2008), 62 (), 375-401CODEN: ARMIAZ; ISSN:0066-4227. (Annual Reviews Inc.)Microbial communities comprise an interwoven matrix of biol. diversity modified by phys. and chem. variation over space and time. Although these communities are the major drivers of biosphere processes, relatively little is known about their structure and function, and predictive modeling is limited by a dearth of comprehensive ecol. principles that describe microbial community processes. Here we discuss working definitions of central ecol. terms that have been used in various fashions in microbial ecol., provide a framework by focusing on different types of interactions within communities, review the status of the interface between evolutionary and ecol. study, and highlight important similarities and differences between macro- and microbial ecol. We describe current approaches to study microbial ecol. and progress toward predictive modeling.
- 166Davies, J.; Spiegelman, G. B.; Yim, G. The world of subinhibitory antibiotic concentrations. Curr. Opin. Microbiol. 2006, 9 (5), 445– 453, DOI: 10.1016/j.mib.2006.08.006Google Scholar166https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XpvFSis7s%253D&md5=ae53c1459f735416c867a892cc01a415The world of subinhibitory antibiotic concentrationsDavies, Julian; Spiegelman, George B.; Yim, GraceCurrent Opinion in Microbiology (2006), 9 (5), 445-453CODEN: COMIF7; ISSN:1369-5274. (Elsevier Ltd.)A review. Although antibiotics have long been known to have multiple effects on bacterial cells at low concns., it is only with the advent of genome transcription analyses that these activities have been studied in detail at the level of cell metab. It has been shown that all antibiotics, regardless of their receptors and mode of action, exhibit the phenomenon of hormesis and provoke considerable transcription activation at low concns. These analyses should be of value in providing information on antibiotic side-effects, in bioactive natural product discovery and antibiotic mode-of-action studies.
- 167Chevrette, M. G.; Thomas, C. S.; Hurley, A.; Rosario-Meléndez, N.; Sankaran, K.; Tu, Y.; Hall, A.; Magesh, S.; Handelsman, J. Microbiome composition modulates secondary metabolism in a multispecies bacterial community. Proc. Natl. Acad. Sci. U.S.A. 2022, 119 (42), e2212930119 DOI: 10.1073/pnas.2212930119Google ScholarThere is no corresponding record for this reference.
- 168Mohimani, H.; Gurevich, A.; Mikheenko, A.; Garg, N.; Nothias, L.-F.; Ninomiya, A.; Takada, K.; Dorrestein, P. C.; Pevzner, P. A. Dereplication of peptidic natural products through database search of mass spectra. Nat. Chem. Biol. 2017, 13 (1), 30– 37, DOI: 10.1038/nchembio.2219Google Scholar168https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhslehur3O&md5=cabf3d72af4f89ffc36933d3a65715e1Dereplication of peptidic natural products through database search of mass spectraMohimani, Hosein; Gurevich, Alexey; Mikheenko, Alla; Garg, Neha; Nothias, Louis-Felix; Ninomiya, Akihiro; Takada, Kentaro; Dorrestein, Pieter C.; Pevzner, Pavel A.Nature Chemical Biology (2017), 13 (1), 30-37CODEN: NCBABT; ISSN:1552-4450. (Nature Publishing Group)Peptidic natural products (PNPs) are widely used compds. that include many antibiotics and a variety of other bioactive peptides. Although recent breakthroughs in PNP discovery raised the challenge of developing new algorithms for their anal., identification of PNPs via database search of tandem mass spectra remains an open problem. To address this problem, natural product researchers use dereplication strategies that identify known PNPs and lead to the discovery of new ones, even in cases when the ref. spectra are not present in existing spectral libraries. DEREPLICATOR is a new dereplication algorithm that enables high-throughput PNP identification and that is compatible with large-scale mass-spectrometry-based screening platforms for natural product discovery. After searching nearly one hundred million tandem mass spectra in the Global Natural Products Social (GNPS) mol. networking infrastructure, DEREPLICATOR identified an order of magnitude more PNPs (and their new variants) than any previous dereplication efforts.
- 169Mohimani, H.; Gurevich, A.; Shlemov, A.; Mikheenko, A.; Korobeynikov, A.; Cao, L.; Shcherbin, E.; Nothias, L.-F.; Dorrestein, P. C.; Pevzner, P. A. Dereplication of microbial metabolites through database search of mass spectra. Nat. Commun. 2018, 9 (1), 4035 DOI: 10.1038/s41467-018-06082-8Google Scholar169https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3czltFyltw%253D%253D&md5=bd0a0706a71d117937789a8dc36095b4Dereplication of microbial metabolites through database search of mass spectraMohimani Hosein; Cao Liu; Mohimani Hosein; Pevzner Pavel A; Gurevich Alexey; Shlemov Alexander; Mikheenko Alla; Korobeynikov Anton; Pevzner Pavel A; Korobeynikov Anton; Shcherbin Egor; Nothias Louis-Felix; Dorrestein Pieter C; Dorrestein Pieter CNature communications (2018), 9 (1), 4035 ISSN:.Natural products have traditionally been rich sources for drug discovery. In order to clear the road toward the discovery of unknown natural products, biologists need dereplication strategies that identify known ones. Here we report DEREPLICATOR+, an algorithm that improves on the previous approaches for identifying peptidic natural products, and extends them for identification of polyketides, terpenes, benzenoids, alkaloids, flavonoids, and other classes of natural products. We show that DEREPLICATOR+ can search all spectra in the recently launched Global Natural Products Social molecular network and identify an order of magnitude more natural products than previous dereplication efforts. We further demonstrate that DEREPLICATOR+ enables cross-validation of genome-mining and peptidogenomics/glycogenomics results.
- 170Cao, L.; Guler, M.; Tagirdzhanov, A.; Lee, Y.-Y.; Gurevich, A.; Mohimani, H. MolDiscovery: Learning Mass Spectrometry Fragmentation of Small Molecules. Nat. Commun. 2021, 12 (1), 3718 DOI: 10.1038/s41467-021-23986-0Google Scholar170https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhsFKgu7bF&md5=7373aab1941e89f63bf8eb0765812279MolDiscovery: learning mass spectrometry fragmentation of small moleculesCao, Liu; Guler, Mustafa; Tagirdzhanov, Azat; Lee, Yi-Yuan; Gurevich, Alexey; Mohimani, HoseinNature Communications (2021), 12 (1), 3718CODEN: NCAOBW; ISSN:2041-1723. (Nature Research)Identification of small mols. is a crit. task in various areas of life science. Recent advances in mass spectrometry have enabled the collection of tandem mass spectra of small mols. from hundreds of thousands of environments. To identify which mols. are present in a sample, one can search mass spectra collected from the sample against millions of mol. structures in small mol. databases. The existing approaches are based on chem. domain knowledge, and they fail to explain many of the peaks in mass spectra of small mols. Here, we present molDiscovery, a mass spectral database search method that improves both efficiency and accuracy of small mol. identification by learning a probabilistic model to match small mols. with their mass spectra. A search of over 8 million spectra from the Global Natural Product Social mol. networking infrastructure shows that molDiscovery correctly identify six times more unique small mols. than previous methods.
- 171Dührkop, K.; Shen, H.; Meusel, M.; Rousu, J.; S, B. Searching Molecular Structure Databases with Tandem Mass Spectra Using CSI:FingerID. Proc. Natl. Acad. Sci. U.S.A. 2015, 112 (41), 12580– 12585, DOI: 10.1073/pnas.1509788112Google Scholar171https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsFamsLzF&md5=8ccf25648836ca6271ebe8516b4c257cSearching molecular structure databases with tandem mass spectra using CSI:FingerIDDuehrkop, Kai; Shen, Huibin; Meusel, Marvin; Rousu, Juho; Boecker, SebastianProceedings of the National Academy of Sciences of the United States of America (2015), 112 (41), 12580-12585CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Metabolites provide a direct functional signature of cellular state. Untargeted metabolomics expts. usually rely on tandem MS to identify the thousands of compds. in a biol. sample. Today, the vast majority of metabolites remain unknown. The authors present a method for searching mol. structure databases using tandem MS data of small mols. The authors' method computes a fragmentation tree that best explains the fragmentation spectrum of an unknown mol. The authors use the fragmentation tree to predict the mol. structure fingerprint of the unknown compd. using machine learning. This fingerprint is then used to search a mol. structure database such as PubChem. The authors' method is shown to improve on the competing methods for computational metabolite identification by a considerable margin.
- 172Pang, Z.; Chong, J.; Zhou, G.; de Lima Morais, D. A.; Chang, L.; Barrette, M.; Gauthier, C.; Jacques, P.-É.; Li, S.; Xia, J. MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights. Nucleic Acids Res. 2021, 49 (W1), W388– W396, DOI: 10.1093/nar/gkab382Google Scholar172https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhvFWgtb3I&md5=2be7e10d38222772b35b35c14aa0f623MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insightsPang, Zhiqiang; Chong, Jasmine; Zhou, Guangyan; Anderson de Lima Morais, David; Chang, Le; Barrette, Michel; Gauthier, Carol; Jacques, Pierre-Etienne; Li, Shuzhao; Xia, JianguoNucleic Acids Research (2021), 49 (W1), W388-W396CODEN: NARHAD; ISSN:1362-4962. (Oxford University Press)Since its first release over a decade ago, the MetaboAnalyst web-based platform has become widely used for comprehensive metabolomics data anal. and interpretation. Here we introduce MetaboAnalyst version 5.0, aiming to narrow the gap from raw data to functional insights for global metabolomics based on high-resoln. mass spectrometry (HRMS). Three modules have been developed to help achieve this goal, including: (i) a LC-MS Spectra Processing module which offers an easy-to-use pipeline that can perform automated parameter optimization and resumable anal. to significantly lower the barriers to LC-MS1 spectra processing; (ii) a Functional Anal. module which expands the previous MS Peaks to Pathways module to allow users to intuitively select any peak groups of interest and evaluate their enrichment of potential functions as defined by metabolic pathways and metabolite sets; (iii) a Functional Meta-Anal. module to combine multiple global metabolomics datasets obtained under complementary conditions or from similar studies to arrive at comprehensive functional insights. There are many other new functions including weighted joint-pathway anal., data-driven network anal., batch effect correction, merging tech. replicates, improved compd. name matching, etc. The web interface, graphics and underlying codebase have also been refactored to improve performance and user experience. At the end of an anal. session, users can now easily switch to other compatible modules for a more streamlined data anal.
- 173Wishart, D. S.; Sayeeda, Z.; Budinski, Z.; Guo, A.; Lee, B. L.; Berjanskii, M.; Rout, M.; Peters, H.; Dizon, R.; Mah, R.; Torres-Calzada, C.; Hiebert-Giesbrecht, M.; Varshavi, D.; Varshavi, D.; Oler, E.; Allen, D.; Cao, X.; Gautam, V.; Maras, A.; Poynton, E. F.; Tavangar, P.; Yang, V.; van Santen, J. A.; Ghosh, R.; Sarma, S.; Knutson, E.; Sullivan, V.; Jystad, A. M.; Renslow, R.; Sumner, L. W.; Linington, R. G.; Cort, J. R. NP-MRD: the Natural Products Magnetic Resonance Database. Nucleic Acids Res. 2022, 50 (D1), D665– D677, DOI: 10.1093/nar/gkab1052Google Scholar173https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38Xis1ChtLc%253D&md5=e7c68d12b29ddd907c490a2914be32b8NP-MRD: the natural products magnetic resonance databaseWishart, David S.; Sayeeda, Zinat; Budinski, Zachary; Guo, AnChi; Lee, Brian L.; Berjanskii, Mark; Rout, Manoj; Peters, Harrison; Dizon, Raynard; Mah, Robert; Torres-Calzada, Claudia; Hiebert-Giesbrecht, Mickel; Varshavi, Dorna; Varshavi, Dorsa; Oler, Eponine; Allen, Dana; Cao, Xuan; Gautam, Vasuk; Maras, Andrew; Poynton, Ella F.; Tavangar, Pegah; Yang, Vera; van Santen, Jeffrey A.; Ghosh, Rajarshi; Sarma, Saurav; Knutson, Eleanor; Sullivan, Victoria; Jystad, Amy M.; Renslow, Ryan; Sumner, Lloyd W.; Linington, Roger G.; Cort, John R.Nucleic Acids Research (2022), 50 (D1), D665-D677CODEN: NARHAD; ISSN:1362-4962. (Oxford University Press)A review. The Natural Products Magnetic Resonance Database (NP-MRD) is a comprehensive, freely available electronic resource for the deposition, distribution, searching and retrieval of NMR (NMR) data on natural products, metabolites and other biol. derived chems. NMR spectroscopy has long been viewed as the 'gold std.' for the structure detn. of novel natural products and novel metabolites. NMR is also widely used in natural product dereplication and the characterization of biofluid mixts. (metabolomics). All of these NMR applications require large collections of high quality, well-annotated, referential NMR spectra of pure compds. Unfortunately, referential NMR spectral collections for natural products are quite limited. It is because of the crit. need for dedicated, open access natural product NMR resources that the NP-MRD was funded by the National Institute of Health (NIH). Since its launch in 2020, the NP-MRD has grown quickly to become the world's largest repository for NMR data on natural products and other biol. substances. It currently contains both structural and NMR data for nearly 41,000 natural product compds. from >7400 different living species. All structural, spectroscopic and descriptive data in the NP-MRD is interactively viewable, searchable and fully downloadable in multiple formats. Extensive hyperlinks to other databases of relevance are also provided. The NP-MRD also supports community deposition of NMR assignments and NMR spectra (1D and 2D) of natural products and related meta-data. The deposition system performs extensive data enrichment, automated data format conversion and spectral/assignment evaluation. Details of these database features, how they are implemented and plans for future upgrades are also provided.
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Abstract
Figure 1
Figure 1. Bacterial isolation and metabolomics workflow. (A) Bacterial isolation from coral mucus, tissue, and the remaining skeleton was performed on six different culture media. Morphologically distinct colonies were isolated and restreaked to ensure purity. (B) Prioritized isolates’ phenotype in mono- and coculture with V. coralliilyticus Cn52-H1. (C) Prioritized strains were cocultured with V. coralliilyticus Cn52-H1, metabolites were extracted using liquid–liquid extraction (LLE), solid phase extraction (SPE), and solid–liquid extraction (SLE). The extracts were analyzed using UPLC-MS and the data was processed for downstream analysis using a suite of cheminformatics tools for compound annotation.
Figure 2
Figure 2. Metabolome profiling of bacterial mono- and cocultures. (A) FBMN showcasing a subset of features that were annotated in this study and their representative chemical structures. The amphibactin cluster and a cluster of unknown metabolites detected in coculture with Microbulbifer sp. CNSA0002 and sharing the MS2LDA motif 531 with the amphibactin cluster are highlighted with a green circle. (B) A Venn diagram representation of the number of features detected across different culture conditions. (C) An UpSet plot is used to show the distribution of 76 features unique to cocultures. (D) PCA plot of untargeted metabolomics data acquired on extracts of V. coralliilyticus Cn52-H1 monoculture, Microbulbifer sp. CNSA002 monoculture and their coculture.
Figure 3
Figure 3. Amphibactin degradation by Microbulbifer sp. CNSA002. (A) MS2LDA motif 531, annotated as containing N-acetyl-N-hydroxy-ornithine. (B) Spectral comparison of amphibactin F and unknown feature with m/z 617.411 produced only in coculture. (C) MS2 mirror plot of amphibactin F and Fe(III)-amphibactin F. No Fe(III)-bound complex of m/z 617.411 was observed. (D) Amphibactin F, produced by V. coralliilyticus Cn52-H1 is degraded in the presence of Microbulbifer sp. CNSA002 cell-free supernatant producing compound 1, structurally elucidated through NMR (Table S4 and Figures S4–S12). Iron-binding hydroxamate moieties are circled. (E) Boxplots of the relative abundances of amphibactin F and its degradation product in their apo- and complex form in monoculture and coculture. (F) Petri plate showing iron chelating activity of purified compound 1 using O-CAS agar assay.
Figure 4
Figure 4. Detection of amphibactins and their degradation products. (A) Boxplots of the relative abundances of amphibactin F (876.529 m/z) and its degradation product (617.412 m/z) in monoculture of V. coralliilyticus Cn52-H1, Microbulbifer sp. CNSA002, their coculture, and Cn52-H1 culture in the presence of cell-free supernatant of CNSA002. (B) Boxplots of relative abundances of degraded amphibactin F in V. coralliilyticus Cn52-H1 cell-free supernatant alone, after boiling, and in the presence of flow through or retentate of an ultrafiltration experiment with either a 3 kDa or 10 kDa membrane. (C) Boxplots of amphibactins and (D) their degradation products in V. coralliilyticus Cn52-H1 monoculture and its coculture with Microbulbifer sp. CNSA002. (E) New amphibactin analogs indirectly identified through their degradation products in Microbulbifer sp. CNSA002 and V. coralliilyticus Cn52-H1 cocultures. The position of double bond was not determined and is putatively placed (shown with dashed line). (F) Boxplots of the relative abundances of amphibactin F and its degradation product in V. coralliilyticus Cn52-H1 monoculture and in coculture with several Microbulbifer sp. strains.
Figure 5
Figure 5. Detection of hydroxamate siderophores and ferrisiderophores in the presence of Microbulbifer sp. CNSA002. (A) Boxplot of the relative abundances of desferrioxamine E and ferrioxamine E (601.356 m/z and 654.267 m/z respectively) in Pseudoalteromonas sp. Cnat2–18.1 and Microbulbifer sp. CNSA002 mono- and coculture. (B) Boxplot of the relative abundances of desferrichrome and ferrichrome (688.326 m/z and 741.237 m/z respectively) when supplemented in a Microbulbifer sp. CNSA002 culture and controls. (C) Representative structures of peptidic hydroxamate siderophores: aquachelin, marinobactin, and moanachelin.
Figure 6
Figure 6. Boxplots of the relative abundances of bulbiferamide A, prodigiosin and bromotryptamine as well as a representative panel of N-acyl amides, in monoculture and coculture conditions. Asterisks indicate significant differences between the compared groups.
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- 23Deutsch, J. M.; Mandelare-Ruiz, P.; Yang, Y.; Foster, G.; Routhu, A.; Houk, J.; De La Flor, Y. T.; Ushijima, B.; Meyer, J. L.; Paul, V. J.; Garg, N. Metabolomics Approaches to Dereplicate Natural Products from Coral-Derived Bioactive Bacteria. J. Nat. Prod. 2022, 85 (3), 462– 478, DOI: 10.1021/acs.jnatprod.1c01110There is no corresponding record for this reference.
- 24Sweet, M.; Villela, H.; Keller-Costa, T.; Costa, R.; Romano, S.; Bourne, D. G.; Cárdenas, A.; Huggett, M. J.; Kerwin, A. H.; Kuek, F.; Medina, M.; Meyer, J. L.; Müller, M.; Pollock, F. J.; Rappé, M. S.; Sere, M.; Sharp, K. H.; Voolstra, C. R.; Zaccardi, N.; Ziegler, M.; Peixoto, R.; Bouskill, N.; Speare, L.; Shore, A. Insights into the Cultured Bacterial Fraction of Corals. mSystems 2021, 6 (3), e0124920 DOI: 10.1128/mSystems.01249-20There is no corresponding record for this reference.
- 25Ziegler, M.; Seneca, F. O.; Yum, L. K.; Palumbi, S. R.; Voolstra, C. R. Bacterial community dynamics are linked to patterns of coral heat tolerance. Nat. Commun. 2017, 8, 14213 DOI: 10.1038/ncomms1421325https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXisVyqtLg%253D&md5=d7025135ee61db463bf96c3426f9562fBacterial community dynamics are linked to patterns of coral heat toleranceZiegler, Maren; Seneca, Francois O.; Yum, Lauren K.; Palumbi, Stephen R.; Voolstra, Christian R.Nature Communications (2017), 8 (), 14213CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)Ocean warming threatens corals and the coral reef ecosystem. Nevertheless, corals can be adapted to their thermal environment and inherit heat tolerance across generations. In addn., the diverse microbes that assoc. with corals have the capacity for more rapid change, potentially aiding the adaptation of long-lived corals. Here, we show that the microbiome of reef corals is different across thermally variable habitats and changes over time when corals are reciprocally transplanted. Exposing these corals to thermal bleaching conditions changes the microbiome for heat-sensitive corals, but not for heat-tolerant corals growing in habitats with natural high heat extremes. Importantly, particular bacterial taxa predict the coral host response in a short-term heat stress expt. Such assocns. could result from parallel responses of the coral and the microbial community to living at high natural temps. A competing hypothesis is that the microbial community and coral heat tolerance are causally linked.
- 26Flórez, L. V.; Biedermann, P. H. W.; Engl, T.; Kaltenpoth, M. Defensive symbioses of animals with prokaryotic and eukaryotic microorganisms. Nat. Prod. Rep. 2015, 32 (7), 904– 936, DOI: 10.1039/C5NP00010FThere is no corresponding record for this reference.
- 27Uria, A.; Piel, J. Cultivation-independent approaches to investigate the chemistry of marine symbiotic bacteria. Phytochem. Rev. 2009, 8 (2), 401– 414, DOI: 10.1007/s11101-009-9127-7There is no corresponding record for this reference.
- 28Ritchie, K. B. Regulation of Microbial Populations by Coral Surface Mucus and Mucus-Associated Bacteria. Mar. Ecol.: Prog. Ser. 2006, 322, 1– 14, DOI: 10.3354/meps32200128https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtlCisLfO&md5=f88503af746c42dfe7537d4b162e57e2Regulation of microbial populations by coral surface mucus and mucus-associated bacteriaRitchie, Kim B.Marine Ecology: Progress Series (2006), 322 (), 1-14CODEN: MESEDT; ISSN:0171-8630. (Inter-Research)Caribbean populations of the elkhorn coral Acropora palmata have declined due to environmental stress, bleaching, and disease. Potential sources of coral mortality include invasive microbes that become trapped in the surface mucus and thrive under conditions of increased coral stress. In this study, mucus from healthy A. palmata inhibited growth of potentially invasive microbes by up to 10-fold. Among cultured bacteria from the mucus of A. palmata, 20% displayed antibiotic activity against one or more tester strains, including the pathogen implicated in white pox disease. A novel mucus-mediated selection for coral symbionts revealed a discrete subset of bacteria and selected for isolates that produce antibiotics. This result suggests that coral mucus plays a role in the structuring of beneficial coral-assocd. microbial communities and implies a microbial contribution to the antibacterial activity described for coral mucus. Interestingly, antibiotic activity was lost when mucus was collected during a summer bleaching event. Isolates from apparently healthy A. palmata tissue during this event lacked antibiotic-producing bacteria and were dominated by members of the genus Vibrio, including species implicated in temp.-dependent bleaching of corals worldwide. This indicates an environmental shift from beneficial bacteria, and variability in the protective qualities of coral mucus, which may lead to an overgrowth of opportunistic microbes when temps. increase. Finally, coral mucus inhibited antibiotic activity and pigment prodn. in a potentially invasive bacterium, illustrating that coral mucus may inactivate mechanisms used for bacterial niche establishment.
- 29Raina, J.-B.; Tapiolas, D.; Motti, C. A.; Foret, S.; Seemann, T.; Tebben, J.; Willis, B. L.; Bourne, D. G. Isolation of an antimicrobial compound produced by bacteria associated with reef-building corals. PeerJ 2016, 4, e2275 DOI: 10.7717/peerj.2275There is no corresponding record for this reference.
- 30Kvennefors, E. C. E.; Sampayo, E.; Kerr, C.; Vieira, G.; Roff, G.; Barnes, A. C. Regulation of Bacterial Communities Through Antimicrobial Activity by the Coral Holobiont. Microb. Ecol. 2012, 63 (3), 605– 618, DOI: 10.1007/s00248-011-9946-0There is no corresponding record for this reference.
- 31Delgadillo-Ordoñez, N.; Garcias-Bonet, N.; Raimundo, I.; García, F. C.; Villela, H.; Osman, E. O.; Santoro, E. P.; Curdia, J.; Rosado, J. G. D.; Cardoso, P.; Alsaggaf, A.; Barno, A.; Antony, C. P.; Bocanegra, C.; Berumen, M. L.; Voolstra, C. R.; Benzoni, F.; Carvalho, S.; Peixoto, R. S. Probiotics reshape the coral microbiome in situ without detectable off-target effects in the surrounding environment. Commun. Biol. 2024, 7 (1), 434 DOI: 10.1038/s42003-024-06135-3There is no corresponding record for this reference.
- 32Papke, E.; Carreiro, A.; Dennison, C.; Deutsch, J. M.; Isma, L. M.; Meiling, S. S.; Rossin, A. M.; Baker, A. C.; Brandt, M. E.; Garg, N.; Holstein, D. M.; Traylor-Knowles, N.; Voss, J. D.; Ushijima, B. Stony coral tissue loss disease: a review of emergence, impacts, etiology, diagnostics, and intervention. Front. Mar. Sci. 2024, 10, 1321271 DOI: 10.3389/fmars.2023.1321271There is no corresponding record for this reference.
- 33Vidal-Dupiol, J.; Ladrière, O.; Meistertzheim, A. L.; Fouré, L.; Adjeroud, M.; Mitta, G. Physiological responses of the scleractinian coral Pocillopora damicornis to bacterial stress from Vibrio coralliilyticus. J. Exp. Biol. 2011, 214 (Pt 9), 1533– 1545, DOI: 10.1242/jeb.053165There is no corresponding record for this reference.
- 34Roder, C.; Arif, C.; Bayer, T.; Aranda, M.; Daniels, C.; Shibl, A.; Chavanich, S.; Voolstra, C. R. Bacterial profiling of White Plague Disease in a comparative coral species framework. Isme J. 2014, 8 (1), 31– 39, DOI: 10.1038/ismej.2013.127There is no corresponding record for this reference.
- 35Ben-Haim, Y.; Zicherman-Keren, M.; Rosenberg, E. Temperature-regulated bleaching and lysis of the coral Pocillopora damicornis by the novel pathogen Vibrio coralliilyticus. Appl. Environ. Microbiol. 2003, 69 (7), 4236– 4242, DOI: 10.1128/AEM.69.7.4236-4242.2003There is no corresponding record for this reference.
- 36Estes, R. M.; Friedman, C. S.; Elston, R. A.; Herwig, R. P. Pathogenicity testing of shellfish hatchery bacterial isolates on Pacific oyster Crassostrea gigas larvae. Dis. Aquat. Org. 2004, 58 (2–3), 223– 230, DOI: 10.3354/dao058223There is no corresponding record for this reference.
- 37Manchanayake, T.; Salleh, A.; Amal, M. N. A.; Yasin, I. S. M.; Zamri-Saad, M. Pathology and pathogenesis of Vibrio infection in fish: A review. Aquacult. Rep. 2023, 28, 101459 DOI: 10.1016/j.aqrep.2022.101459There is no corresponding record for this reference.
- 38Vizcaino, M. I.; Johnson, W. R.; Kimes, N. E.; Williams, K.; Torralba, M.; Nelson, K. E.; Smith, G. W.; Weil, E.; Moeller, P. D.; Morris, P. J. Antimicrobial resistance of the coral pathogen Vibrio coralliilyticus and Caribbean sister phylotypes isolated from a diseased octocoral. Microb. Ecol. 2010, 59 (4), 646– 657, DOI: 10.1007/s00248-010-9644-3There is no corresponding record for this reference.
- 39Ushijima, B.; Meyer, J. L.; Thompson, S.; Pitts, K.; Marusich, M. F.; Tittl, J.; Weatherup, E.; Reu, J.; Wetzell, R.; Aeby, G. S.; Häse, C. C.; Paul, V. J. Disease Diagnostics and Potential Coinfections by Vibrio coralliilyticus During an Ongoing Coral Disease Outbreak in Florida. Front. Microbiol. 2020, 11, 569354 DOI: 10.3389/fmicb.2020.569354There is no corresponding record for this reference.
- 40Heinz, J. M.; Lu, J.; Huebner, L. K.; Salzberg, S. L.; Sommer, M.; Rosales, S. M. Novel metagenomics analysis of stony coral tissue loss disease bioRxiv: The Preprint Server for Biology 2024 DOI: 10.1101/2024.01.02.573916 .There is no corresponding record for this reference.
- 41Meyer, J. L.; Castellanos-Gell, J.; Aeby, G. S.; Häse, C. C.; Ushijima, B.; Paul, V. J. Microbial Community Shifts Associated With the Ongoing Stony Coral Tissue Loss Disease Outbreak on the Florida Reef Tract. Front. Microbiol. 2019, 10, 2244 DOI: 10.3389/fmicb.2019.02244There is no corresponding record for this reference.
- 42Shilling, E. N.; Combs, I. R.; Voss, J. D. Assessing the effectiveness of two intervention methods for stony coral tissue loss disease on Montastraea cavernosa. Sci. Rep. 2021, 11 (1), 8566 DOI: 10.1038/s41598-021-86926-4There is no corresponding record for this reference.
- 43Studivan, M. S.; Eckert, R. J.; Shilling, E.; Soderberg, N.; Enochs, I. C.; Voss, J. D. Stony coral tissue loss disease intervention with amoxicillin leads to a reversal of disease-modulated gene expression pathways. Mol. Ecol. 2023, 32 (19), 5394– 5413, DOI: 10.1111/mec.17110There is no corresponding record for this reference.
- 44Rubio-Portillo, E.; Santos, F.; Martínez-García, M.; de Los Ríos, A.; Ascaso, C.; Souza-Egipsy, V.; Ramos-Esplá, A. A.; Anton, J. Structure and temporal dynamics of the bacterial communities associated to microhabitats of the coral Oculina patagonica. Environ. Microbiol. 2016, 18 (12), 4564– 4578, DOI: 10.1111/1462-2920.13548There is no corresponding record for this reference.
- 45Sunagawa, S.; Coelho, L. P.; Chaffron, S.; Kultima, J. R.; Labadie, K.; Salazar, G.; Djahanschiri, B.; Zeller, G.; Mende, D. R.; Alberti, A.; Cornejo-Castillo, F. M.; Costea, P. I.; Cruaud, C.; d’Ovidio, F.; Engelen, S.; Ferrera, I.; Gasol, J. M.; Guidi, L.; Hildebrand, F.; Kokoszka, F.; Lepoivre, C.; Lima-Mendez, G.; Poulain, J.; Poulos, B. T.; Royo-Llonch, M.; Sarmento, H.; Vieira-Silva, S.; Dimier, C.; Picheral, M.; Searson, S.; Kandels-Lewis, S.; Oceans, T.; Bowler, C.; de Vargas, C.; Gorsky, G.; Grimsley, N.; Hingamp, P.; Iudicone, D.; Jaillon, O.; Not, F.; Ogata, H.; Pesant, S.; Speich, S.; Stemmann, L.; Sullivan, M. B.; Weissenbach, J.; Wincker, P.; Karsenti, E.; Raes, J.; Acinas, S. G.; Bork, P.; Boss, E.; Bowler, C.; Follows, M.; Karp-Boss, L.; Krzic, U.; Reynaud, E. G.; Sardet, C.; Sieracki, M.; Velayoudon, D. Structure and function of the global ocean microbiome. Science 2015, 348 (6237), 1261359 DOI: 10.1126/science.126135945https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2MfmsVKgtQ%253D%253D&md5=55c0d91e78a4772180b6d5bd6f1769d9Ocean plankton. Structure and function of the global ocean microbiomeSunagawa Shinichi; Coelho Luis Pedro; Kultima Jens Roat; Djahanschiri Bardya; Zeller Georg; Mende Daniel R; Costea Paul I; Hildebrand Falk; Chaffron Samuel; Lima-Mendez Gipsi; Vieira-Silva Sara; Raes Jeroen; Labadie Karine; Alberti Adriana; Cruaud Corinne; Engelen Stefan; Poulain Julie; Salazar Guillem; Cornejo-Castillo Francisco M; Ferrera Isabel; Gasol Josep M; Royo-Llonch Marta; Acinas Silvia G; d'Ovidio Francesco; Guidi Lionel; Picheral Marc; Searson Sarah; Gorsky Gabriel; Stemmann Lars; Kokoszka Florian; Lepoivre Cyrille; Hingamp Pascal; Poulos Bonnie T; Sullivan Matthew B; Sarmento Hugo; Dimier Celine; Kandels-Lewis Stefanie; Bowler Chris; de Vargas Colomban; Not Fabrice; Grimsley Nigel; Iudicone Daniele; Jaillon Olivier; Weissenbach Jean; Wincker Patrick; Ogata Hiroyuki; Pesant Stephane; Speich Sabrina; Karsenti Eric; Bork PeerScience (New York, N.Y.) (2015), 348 (6237), 1261359 ISSN:.Microbes are dominant drivers of biogeochemical processes, yet drawing a global picture of functional diversity, microbial community structure, and their ecological determinants remains a grand challenge. We analyzed 7.2 terabases of metagenomic data from 243 Tara Oceans samples from 68 locations in epipelagic and mesopelagic waters across the globe to generate an ocean microbial reference gene catalog with >40 million nonredundant, mostly novel sequences from viruses, prokaryotes, and picoeukaryotes. Using 139 prokaryote-enriched samples, containing >35,000 species, we show vertical stratification with epipelagic community composition mostly driven by temperature rather than other environmental factors or geography. We identify ocean microbial core functionality and reveal that >73% of its abundance is shared with the human gut microbiome despite the physicochemical differences between these two ecosystems.
- 46Su, H.; Xiao, Z.; Yu, K.; Huang, Q.; Wang, G.; Wang, Y.; Liang, J.; Huang, W.; Huang, X.; Wei, F.; Chen, B. Diversity of cultivable protease-producing bacteria and their extracellular proteases associated to scleractinian corals. PeerJ 2020, 8, e9055 DOI: 10.7717/peerj.9055There is no corresponding record for this reference.
- 47Wei, Y.; Bu, J.; Long, H.; Zhang, X.; Cai, X.; Huang, A.; Ren, W.; Xie, Z. Community Structure of Protease-Producing Bacteria Cultivated From Aquaculture Systems: Potential Impact of a Tropical Environment. Front. Microbiol. 2021, 12, 638129 DOI: 10.3389/fmicb.2021.638129There is no corresponding record for this reference.
- 48Zhou, M.-Y.; Wang, G.-L.; Li, D.; Zhao, D.-L.; Qin, Q.-L.; Chen, X.-L.; Chen, B.; Zhou, B.-C.; Zhang, X.-Y.; Zhang, Y.-Z. Diversity of Both the Cultivable Protease-Producing Bacteria and Bacterial Extracellular Proteases in the Coastal Sediments of King George Island, Antarctica. PLoS One 2013, 8 (11), e79668 DOI: 10.1371/journal.pone.0079668There is no corresponding record for this reference.
- 49Cristóbal, H. A.; López, M. A.; Kothe, E.; Abate, C. M. Diversity of protease-producing marine bacteria from sub-antarctic environments. J. Basic Microbiol. 2011, 51 (6), 590– 600, DOI: 10.1002/jobm.201000413There is no corresponding record for this reference.
- 50Zhang, J.; Chen, M.; Huang, J.; Guo, X.; Zhang, Y.; Liu, D.; Wu, R.; He, H.; Wang, J. Diversity of the microbial community and cultivable protease-producing bacteria in the sediments of the Bohai Sea, Yellow Sea and South China Sea. PLoS One 2019, 14 (4), e0215328 DOI: 10.1371/journal.pone.0215328There is no corresponding record for this reference.
- 51Paulsen, S. S.; Strube, M. L.; Bech, P. K.; Gram, L.; Sonnenschein, E. C. Marine Chitinolytic Pseudoalteromonas Represents an Untapped Reservoir of Bioactive Potential. mSystems 2019, 4 (4), e00060-19 DOI: 10.1128/mSystems.00060-19There is no corresponding record for this reference.
- 52Cimermancic, P.; Medema, M. H.; Claesen, J.; Kurita, K.; Brown, L. C. W.; Mavrommatis, K.; Pati, A.; Godfrey, P. A.; Koehrsen, M.; Clardy, J.; Birren, B. W.; Takano, E.; Sali, A.; Linington, R. G.; Fischbach, M. A. Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters. Cell 2014, 158 (2), 412– 421, DOI: 10.1016/j.cell.2014.06.03452https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFyjtLfM&md5=de090354acacade81ebfb103e57200d5Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clustersCimermancic, Peter; Medema, Marnix H.; Claesen, Jan; Kurita, Kenji; Wieland Brown, Laura C.; Mavrommatis, Konstantinos; Pati, Amrita; Godfrey, Paul A.; Koehrsen, Michael; Clardy, Jon; Birren, Bruce W.; Takano, Eriko; Sali, Andrej; Linington, Roger G.; Fischbach, Michael A.Cell (Cambridge, MA, United States) (2014), 158 (2), 412-421CODEN: CELLB5; ISSN:0092-8674. (Cell Press)Although biosynthetic gene clusters (BGCs) have been discovered for hundreds of bacterial metabolites, our knowledge of their diversity remains limited. Here, we used a novel algorithm to systematically identify BGCs in the extensive extant microbial sequencing data. Network anal. of the predicted BGCs revealed large gene cluster families, the vast majority uncharacterized. We exptl. characterized the most prominent family, consisting of two subfamilies of hundreds of BGCs distributed throughout the Proteobacteria; their products are aryl polyenes, lipids with an aryl head group conjugated to a polyene tail. We identified a distant relationship to a third subfamily of aryl polyene BGCs, and together the three subfamilies represent the largest known family of biosynthetic gene clusters, with more than 1000 members. Although these clusters are widely divergent in sequence, their small mol. products are remarkably conserved, indicating for the first time the important roles these compds. play in Gram-neg. cell biol.
- 53Buijs, Y.; Bech, P. K.; Vazquez-Albacete, D.; Bentzon-Tilia, M.; Sonnenschein, E. C.; Gram, L.; Zhang, S.-D. Marine Proteobacteria as a source of natural products: advances in molecular tools and strategies. Nat. Prod. Rep. 2019, 36 (9), 1333– 1350, DOI: 10.1039/C9NP00020HThere is no corresponding record for this reference.
- 54Baba, A.; Miyazaki, M.; Nagahama, T.; Nogi, Y. Microbulbifer chitinilyticus sp. nov. and Microbulbifer okinawensis sp. nov., chitin-degrading bacteria isolated from mangrove forests. Int. J. Syst. Evol. Microbiol. 2011, 61 (Pt 9), 2215– 2220, DOI: 10.1099/ijs.0.024158-0There is no corresponding record for this reference.
- 55Miyazaki, M.; Nogi, Y.; Ohta, Y.; Hatada, Y.; Fujiwara, Y.; Ito, S.; Horikoshi, K. Microbulbifer agarilyticus sp. nov. and Microbulbifer thermotolerans sp. nov., agar-degrading bacteria isolated from deep-sea sediment. Int. J. Syst. Evol. Microbiol. 2008, 58, 1128– 1133, DOI: 10.1099/ijs.0.65507-0There is no corresponding record for this reference.
- 56Vashist, P.; Nogi, Y.; Ghadi, S. C.; Verma, P.; Shouche, Y. S. Microbulbifer mangrovi sp. nov., a polysaccharide-degrading bacterium isolated from an Indian mangrove. Int. J. Syst. Evol. Microbiol. 2013, 63, 2532– 2537, DOI: 10.1099/ijs.0.042978-0There is no corresponding record for this reference.
- 57González, J. M.; Mayer, F.; Moran, M. A.; Hodson, R. E.; Whitman, W. B. Microbulbifer hydrolyticus gen. nov., sp. nov., and Marinobacterium georgiense gen. nov., sp. nov., two marine bacteria from a lignin-rich pulp mill waste enrichment community. Int. J. Syst. Bacteriol. 1997, 47 (2), 369– 376, DOI: 10.1099/00207713-47-2-369There is no corresponding record for this reference.
- 58Lee, Y. S. Isolation and Characterization of a Novel Cold-Adapted Esterase, MtEst45, from Microbulbifer thermotolerans DAU221. Front. Microbiol. 2016, 7, 218 DOI: 10.3389/fmicb.2016.00218There is no corresponding record for this reference.
- 59Jayanetti, D. R.; Braun, D. R.; Barns, K. J.; Rajski, S. R.; Bugni, T. S. Bulbiferates A and B: Antibacterial Acetamidohydroxybenzoates from a Marine Proteobacterium, Microbulbifer sp. J. Nat. Prod. 2019, 82 (7), 1930– 1934, DOI: 10.1021/acs.jnatprod.9b00312There is no corresponding record for this reference.
- 60Lu, S.; Zhang, Z.; Sharma, A. R.; Nakajima-Shimada, J.; Harunari, E.; Oku, N.; Trianto, A.; Igarashi, Y. Bulbiferamide, an Antitrypanosomal Hexapeptide Cyclized via an N-Acylindole Linkage from a Marine Obligate Microbulbifer. J. Nat. Prod. 2023, 86 (4), 1081– 1086, DOI: 10.1021/acs.jnatprod.2c0108360https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXjslKrsb0%253D&md5=6e69f4d0d21896f1ef828265d0fc69c1Bulbiferamide, an Antitrypanosomal Hexapeptide Cyclized via an N-Acylindole Linkage from a Marine Obligate MicrobulbiferLu, Shiyang; Zhang, Zhiwei; Sharma, Amit Raj; Nakajima-Shimada, Junko; Harunari, Enjuro; Oku, Naoya; Trianto, Agus; Igarashi, YasuhiroJournal of Natural Products (2023), 86 (4), 1081-1086CODEN: JNPRDF; ISSN:0163-3864. (American Chemical Society-American Society of Pharmacognosy)UV absorption spectroscopy-guided fractionation of the culture ext. of a marine obligate bacterium of the genus Microbulbifer yielded a novel cyclic hexapeptide, bulbiferamide. NMR spectroscopic and mass spectrometric analyses revealed the structure of bulbiferamide to be a cyclic tetrapeptide appending a ureido-bridged two amino acid unit. Notably, Trp is a junction residue, forming on one hand a very rare N-aminoacylated indole linkage for cyclization and on the other hand connecting the ureido-contg. tail structure, which is an unprecedented way of configuring peptides. The component amino acids were detd. to be L by the advanced Marfey's method. Bulbiferamide displayed growth inhibitory activity against Trypanosoma cruzi epimastigotes with an IC50 value of 4.1 μM, comparable to the currently approved drug benznidazole, while it was not cytotoxic to P388 murine leukemia cells at 100 μM.
- 61Zhong, W.; Deutsch, J. M.; Yi, D.; Abrahamse, N. H.; Mohanty, I.; Moore, S. G.; McShan, A. C.; Garg, N.; Agarwal, V. Discovery and Biosynthesis of Ureidopeptide Natural Products Macrocyclized via Indole N-acylation in Marine Microbulbifer spp. Bacteria. ChemBioChem 2023, 24 (12), e202300190 DOI: 10.1002/cbic.20230019061https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhtVSit73F&md5=928d657bc587255525a02b9b3815e585Discovery and Biosynthesis of Ureidopeptide Natural Products Macrocyclized via Indole N-acylation in Marine Microbulbifer spp. BacteriaZhong, Weimao; Deutsch, Jessica M.; Yi, Dongqi; Abrahamse, Nadine H.; Mohanty, Ipsita; Moore, Samuel G.; McShan, Andrew C.; Garg, Neha; Agarwal, VinayakChemBioChem (2023), 24 (12), e202300190CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)Commensal bacteria assocd. with marine invertebrates are underappreciated sources of chem. novel natural products. Using mass spectrometry, we had previously detected the presence of peptidic natural products in obligate marine bacteria of the genus Microbulbifer cultured from marine sponges. In this report, the isolation and structural characterization of a panel of ureidohexapeptide natural products, termed the bulbiferamides, from Microbulbifer strains is reported wherein the tryptophan side chain indole participates in a macrocyclizing peptide bond formation. Genome sequencing identifies biosynthetic gene clusters encoding prodn. of the bulbiferamides and implicates the involvement of a thioesterase in the indolic macrocycle formation. The structural diversity and widespread presence of bulbiferamides in commensal microbiomes of marine invertebrates point toward a possible ecol. role for these natural products.
- 62Zhong, W.; Aiosa, N.; Deutsch, J. M.; Garg, N.; Agarwal, V. Pseudobulbiferamides: Plasmid-Encoded Ureidopeptide Natural Products with Biosynthetic Gene Clusters Shared Among Marine Bacteria of Different Genera. J. Nat. Prod. 2023, 86 (10), 2414– 2420, DOI: 10.1021/acs.jnatprod.3c00595There is no corresponding record for this reference.
- 63Zhong, W.; Agarwal, V. Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty. Beilstein J. Org. Chem. 2024, 20, 1635– 1651, DOI: 10.3762/bjoc.20.146There is no corresponding record for this reference.
- 64Mawji, E.; Gledhill, M.; Milton, J. A.; Tarran, G. A.; Ussher, S.; Thompson, A.; Wolff, G. A.; Worsfold, P. J.; Achterberg, E. P. Hydroxamate siderophores: occurrence and importance in the Atlantic Ocean. Environ. Sci. Technol. 2008, 42 (23), 8675– 8680, DOI: 10.1021/es801884r64https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhtlWqurzI&md5=392e690d8a01954b78dd82fd9fb1dad2Hydroxamate Siderophores: Occurrence and Importance in the Atlantic OceanMawji, Edward; Gledhill, Martha; Milton, James A.; Tarran, Glen A.; Ussher, Simon; Thompson, Anu; Wolff, George A.; Worsfold, Paul J.; Achterberg, Eric P.Environmental Science & Technology (2008), 42 (23), 8675-8680CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)Siderophores are bacteria-produced chelates as part of a highly specific Fe uptake mechanism. They are thought to be important in the bacterial acquisition of Fe from seawater and affect Fe biogeochem. in the ocean. We have identified and quantified two types of siderophores in seawater samples collected from the Atlantic Ocean. The authors identified and quantified 2 types of siderophores in seawater collected from the Atlantic Ocean. These siderophores were identified as hydroxamate siderophores, both ferrioxamine species representative of the more sol. marine siderophores characterized to date. Ferrioxamine G is widely distributed in surface water throughout the Atlantic ferrioxamine E has a more varied distribution. Total concns. of these 2 siderophores is 3-20 pM in the euphotic zone. If these compds. are fully complexed in seawater, they represent ∼0.2-4.6% of the <0.2 μm Fe pool. Data confirmed siderophore-mediated Fe acquisition is important for marine heterotrophic bacteria and indicated siderophores play an important role in the oceanic biogeochem. Fe cycling.
- 65Boiteau, R. M.; Mende, D. R.; Hawco, N. J.; McIlvin, M. R.; Fitzsimmons, J. N.; Saito, M. A.; Sedwick, P. N.; DeLong, E. F.; Repeta, D. J. Siderophore-Based Microbial Adaptations to Iron Scarcity Across the Eastern Pacific Ocean. Proc. Natl. Acad. Sci. U.S.A. 2016, 113 (50), 14237– 14242, DOI: 10.1073/pnas.160859411365https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvFOgs7rK&md5=7ad913c2e3a5ca860b8eb7431d4a91b4Siderophore-based microbial adaptations to iron scarcity across the eastern Pacific OceanBoiteau, Rene M.; Mende, Daniel R.; Hawco, Nicholas J.; McIlvin, Matthew R.; Fitzsimmons, Jessica N.; Saito, Mak A.; Sedwick, Peter N.; DeLong, Edward F.; Repeta, Daniel J.Proceedings of the National Academy of Sciences of the United States of America (2016), 113 (50), 14237-14242CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Nearly all iron dissolved in the ocean is complexed by strong org. ligands of unknown compn. The effect of ligand compn. on microbial iron acquisition is poorly understood, but amendment expts. using model ligands show they can facilitate or impede iron uptake depending on their identity. Here we show that siderophores, org. compds. synthesized by microbes to facilitate iron uptake, are a dynamic component of the marine ligand pool in the eastern tropical Pacific Ocean. Siderophore concns. in iron-deficient waters averaged 9 pM, up to fivefold higher than in iron-rich coastal and nutrient-depleted oligotrophic waters, and were dominated by amphibactins, amphiphilic siderophores with cell membrane affinity. Phylogenetic anal. of amphibactin biosynthetic genes suggests that the ability to produce amphibactins has transferred horizontally across multiple Gammaproteobacteria, potentially driven by pressures to compete for iron. In coastal and oligotrophic regions of the eastern Pacific Ocean, amphibactins were replaced with lower concns. (1-2 pM) of hydrophilic ferrioxamine siderophores. Our results suggest that org. ligand compn. changes across the surface ocean in response to environmental pressures. Hydrophilic siderophores are predominantly found across regions of the ocean where iron is not expected to be the limiting nutrient for the microbial community at large. However, in regions with intense competition for iron, some microbes optimize iron acquisition by producing siderophores that minimize diffusive losses to the environment. These siderophores affect iron bioavailability and thus may be an important component of the marine iron cycle.
- 66Deutsch, J. M.; Green, M. O.; Akavaram, P.; Davis, A. C.; Diskalkar, S. S.; Du Plessis, I. A.; Fallon, H. A.; Grason, E. M.; Kauf, E. G.; Kim, Z. M.; Miller, J. R.; Neal, A. L.; Riera, T.; Stroeva, S.-E.; Tran, J.; Tran, V.; Coronado, A. V.; Coronado, V. V.; Wall, B. T.; Yang, Cm.; Mohanty, I.; Abrahamse, N. H.; Freeman, C. J.; Easson, C. G.; Fiore, C. L.; Onstine, A. E.; Djeddar, N.; Biliya, S.; Bryksin, A. V.; Garg, N.; Agarwal, V. Limited Metabolomic Overlap between Commensal Bacteria and Marine Sponge Holobionts Revealed by Large Scale Culturing and Mass Spectrometry-Based Metabolomics: An Undergraduate Laboratory Pedagogical Effort at Georgia Tech. Mar. Drugs 2023, 21 (1), 53 DOI: 10.3390/md21010053There is no corresponding record for this reference.
- 67Buijs, Y.; Isbrandt, T.; Zhang, S.-D.; Larsen, T. O.; Gram, L. The Antibiotic Andrimid Produced by Vibrio coralliilyticus Increases Expression of Biosynthetic Gene Clusters and Antibiotic Production in Photobacterium galatheae. Front. Microbiol. 2020, 11, 622055 DOI: 10.3389/fmicb.2020.622055There is no corresponding record for this reference.
- 68Pluskal, T.; Castillo, S.; Villar-Briones, A.; Orešič, M. MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinf. 2010, 11 (1), 395 DOI: 10.1186/1471-2105-11-39568https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3cjjsVymsA%253D%253D&md5=e6e2ac996767f8526daccbdb7f4929e0MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile dataPluskal Tomas; Castillo Sandra; Villar-Briones Alejandro; Oresic MatejBMC bioinformatics (2010), 11 (), 395 ISSN:.BACKGROUND: Mass spectrometry (MS) coupled with online separation methods is commonly applied for differential and quantitative profiling of biological samples in metabolomic as well as proteomic research. Such approaches are used for systems biology, functional genomics, and biomarker discovery, among others. An ongoing challenge of these molecular profiling approaches, however, is the development of better data processing methods. Here we introduce a new generation of a popular open-source data processing toolbox, MZmine 2. RESULTS: A key concept of the MZmine 2 software design is the strict separation of core functionality and data processing modules, with emphasis on easy usability and support for high-resolution spectra processing. Data processing modules take advantage of embedded visualization tools, allowing for immediate previews of parameter settings. Newly introduced functionality includes the identification of peaks using online databases, MSn data support, improved isotope pattern support, scatter plot visualization, and a new method for peak list alignment based on the random sample consensus (RANSAC) algorithm. The performance of the RANSAC alignment was evaluated using synthetic datasets as well as actual experimental data, and the results were compared to those obtained using other alignment algorithms. CONCLUSIONS: MZmine 2 is freely available under a GNU GPL license and can be obtained from the project website at: http://mzmine.sourceforge.net/. The current version of MZmine 2 is suitable for processing large batches of data and has been applied to both targeted and non-targeted metabolomic analyses.
- 69Wang, M.; Carver, J. J.; Phelan, V. V.; Sanchez, L. M.; Garg, N.; Peng, Y.; Nguyen, D. D.; Watrous, J.; Kapono, C. A.; Luzzatto-Knaan, T.; Porto, C.; Bouslimani, A.; Melnik, A. V.; Meehan, M. J.; Liu, W.-T.; Crüsemann, M.; Boudreau, P. D.; Esquenazi, E.; Sandoval-Calderón, M.; Kersten, R. D.; Pace, L. A.; Quinn, R. A.; Duncan, K. R.; Hsu, C.-C.; Floros, D. J.; Gavilan, R. G.; Kleigrewe, K.; Northen, T.; Dutton, R. J.; Parrot, D.; Carlson, E. E.; Aigle, B.; Michelsen, C. F.; Jelsbak, L.; Sohlenkamp, C.; Pevzner, P.; Edlund, A.; McLean, J.; Piel, J.; Murphy, B. T.; Gerwick, L.; Liaw, C.-C.; Yang, Y.-L.; Humpf, H.-U.; Maansson, M.; Keyzers, R. A.; Sims, A. C.; Johnson, A. R.; Sidebottom, A. M.; Sedio, B. E.; Klitgaard, A.; Larson, C. B.; Boya P, C. A.; Torres-Mendoza, D.; Gonzalez, D. J.; Silva, D. B.; Marques, L. M.; Demarque, D. P.; Pociute, E.; O’Neill, E. C.; Briand, E.; Helfrich, E. J. N.; Granatosky, E. A.; Glukhov, E.; Ryffel, F.; Houson, H.; Mohimani, H.; Kharbush, J. J.; Zeng, Y.; Vorholt, J. A.; Kurita, K. L.; Charusanti, P.; McPhail, K. L.; Nielsen, K. F.; Vuong, L.; Elfeki, M.; Traxler, M. F.; Engene, N.; Koyama, N.; Vining, O. B.; Baric, R.; Silva, R. R.; Mascuch, S. J.; Tomasi, S.; Jenkins, S.; Macherla, V.; Hoffman, T.; Agarwal, V.; Williams, P. G.; Dai, J.; Neupane, R.; Gurr, J.; Rodríguez, A. M. C.; Lamsa, A.; Zhang, C.; Dorrestein, K.; Duggan, B. M.; Almaliti, J.; Allard, P.-M.; Phapale, P.; Nothias, L.-F.; Alexandrov, T.; Litaudon, M.; Wolfender, J.-L.; Kyle, J. E.; Metz, T. O.; Peryea, T.; Nguyen, D.-T.; VanLeer, D.; Shinn, P.; Jadhav, A.; Müller, R.; Waters, K. M.; Shi, W.; Liu, X.; Zhang, L.; Knight, R.; Jensen, P. R.; Palsson, B. Ø.; Pogliano, K.; Linington, R. G.; Gutiérrez, M.; Lopes, N. P.; Gerwick, W. H.; Moore, B. S.; Dorrestein, P. C.; Bandeira, N. Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nat. Biotechnol. 2016, 34 (8), 828– 837, DOI: 10.1038/nbt.359769https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlaitLnE&md5=e6ca23ede2d85dd1460a5d73da542444Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular NetworkingWang, Mingxun; Carver, Jeremy J.; Phelan, Vanessa V.; Sanchez, Laura M.; Garg, Neha; Peng, Yao; Nguyen, Don Duy; Watrous, Jeramie; Kapono, Clifford A.; Luzzatto-Knaan, Tal; Porto, Carla; Bouslimani, Amina; Melnik, Alexey V.; Meehan, Michael J.; Liu, Wei-Ting; Crusemann, Max; Boudreau, Paul D.; Esquenazi, Eduardo; Sandoval-Calderon, Mario; Kersten, Roland D.; Pace, Laura A.; Quinn, Robert A.; Duncan, Katherine R.; Hsu, Cheng-Chih; Floros, Dimitrios J.; Gavilan, Ronnie G.; Kleigrewe, Karin; Northen, Trent; Dutton, Rachel J.; Parrot, Delphine; Carlson, Erin E.; Aigle, Bertrand; Michelsen, Charlotte F.; Jelsbak, Lars; Sohlenkamp, Christian; Pevzner, Pavel; Edlund, Anna; McLean, Jeffrey; Piel, Jorn; Murphy, Brian T.; Gerwick, Lena; Liaw, Chih-Chuang; Yang, Yu-Liang; Humpf, Hans-Ulrich; Maansson, Maria; Keyzers, Robert A.; Sims, Amy C.; Johnson, Andrew R.; Sidebottom, Ashley M.; Sedio, Brian E.; Klitgaard, Andreas; Larson, Charles B.; Boya P, Cristopher A.; Torres-Mendoza, Daniel; Gonzalez, David J.; Silva, Denise B.; Marques, Lucas M.; Demarque, Daniel P.; Pociute, Egle; O'Neill, Ellis C.; Briand, Enora; Helfrich, Eric J. N.; Granatosky, Eve A.; Glukhov, Evgenia; Ryffel, Florian; Houson, Hailey; Mohimani, Hosein; Kharbush, Jenan J.; Zeng, Yi; Vorholt, Julia A.; Kurita, Kenji L.; Charusanti, Pep; McPhail, Kerry L.; Nielsen, Kristian Fog; Vuong, Lisa; Elfeki, Maryam; Traxler, Matthew F.; Engene, Niclas; Koyama, Nobuhiro; Vining, Oliver B.; Baric, Ralph; Silva, Ricardo R.; Mascuch, Samantha J.; Tomasi, Sophie; Jenkins, Stefan; Macherla, Venkat; Hoffman, Thomas; Agarwal, Vinayak; Williams, Philip G.; Dai, Jingqui; Neupane, Ram; Gurr, Joshua; Rodriguez, Andres M. C.; Lamsa, Anne; Zhang, Chen; Dorrestein, Kathleen; Duggan, Brendan M.; Almaliti, Jehad; Allard, Pierre-Marie; Phapale, Prasad; Nothias, Louis-Felix; Alexandrov, Theodore; Litaudon, Marc; Wolfender, Jean-Luc; Kyle, Jennifer E.; Metz, Thomas O.; Peryea, Tyler; Nguyen, Dac-Trung; Van Leer, Danielle; Shinn, Paul; Jadhav, Ajit; Muller, Rolf; Waters, Katrina M.; Shi, Wenyuan; Liu, Xueting; Zhang, Lixin; Knight, Rob; Jensen, Paul R.; Palsson, Bernhard O.; Pogliano, Kit; Linington, Roger G.; Gutierrez, Marcelino; Lopes, Norberto P.; Gerwick, William H.; Moore, Bradley S.; Dorrestein, Pieter C.; Bandeira, NunoNature Biotechnology (2016), 34 (8), 828-837CODEN: NABIF9; ISSN:1087-0156. (Nature Publishing Group)The potential of the diverse chemistries present in natural products (NP) for biotechnol. and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry (MS) techniques are well-suited to high-throughput characterization of NP, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social Mol. Networking (GNPS; http://gnps.ucsd.edu), an open-access knowledge base for community-wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS, crowdsourced curation of freely available community-wide ref. MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of 'living data' through continuous reanal. of deposited data.
- 70Shannon, P.; Markie, A.; Ozier, O.; Baliga, N. S.; Wang, J. T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks. Genome Res. 2003, 13, 2498– 2504, DOI: 10.1101/gr.123930370https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXovFWrtr4%253D&md5=2bcbca9a3bd04717761f0424c0209e43Cytoscape: A software environment for integrated models of biomolecular interaction networksShannon, Paul; Markiel, Andrew; Ozier, Owen; Baliga, Nitin S.; Wang, Jonathan T.; Ramage, Daniel; Amin, Nada; Schwikowski, Benno; Ideker, TreyGenome Research (2003), 13 (11), 2498-2504CODEN: GEREFS; ISSN:1088-9051. (Cold Spring Harbor Laboratory Press)Cytoscape is an open source software project for integrating biomol. interaction networks with high-throughput expression data and other mol. states into a unified conceptual framework. Although applicable to any system of mol. components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other mol. states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of addnl. computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined phys./functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
- 71Khan, A.; Mathelier, A. Intervene: a tool for intersection and visualization of multiple gene or genomic region sets. BMC Bioinf. 2017, 18 (1), 287 DOI: 10.1186/s12859-017-1708-7There is no corresponding record for this reference.
- 72Dührkop, K.; Fleischauer, M.; Ludwig, M.; Aksenov, A. A.; Melnik, A. V. SIRIUS 4: A Rapid Tool for Turning Tandem Mass Spectra into Metabolite Structure Information. Nat. Methods 2019, 16, 299– 302, DOI: 10.1038/s41592-019-0344-872https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmslKgurg%253D&md5=9f47c714d2412974315fcde740227da3SIRIUS 4: a rapid tool for turning tandem mass spectra into metabolite structure informationDuehrkop, Kai; Fleischauer, Markus; Ludwig, Marcus; Aksenov, Alexander A.; Melnik, Alexey V.; Meusel, Marvin; Dorrestein, Pieter C.; Rousu, Juho; Boecker, SebastianNature Methods (2019), 16 (4), 299-302CODEN: NMAEA3; ISSN:1548-7091. (Nature Research)Mass spectrometry is a predominant exptl. technique in metabolomics and related fields, but metabolite structural elucidation remains highly challenging. We report SIRIUS 4 (https://bio.informatik.uni-jena.de/sirius/), which provides a fast computational approach for mol. structure identification. SIRIUS 4 integrates CSI:FingerID for searching in mol. structure databases. Using SIRIUS 4, we achieved identification rates of more than 70% on challenging metabolomics datasets.
- 73Dührkop, K.; Nothias, L.-F.; Fleischauer, M.; Reher, R.; Ludwig, M.; Hoffmann, M. A.; Petras, D.; Gerwick, W. H.; Rousu, J.; Dorrestein, P. C.; Böcker, S. Systematic Classification of Unknown Metabolites Using High-Resolution Fragmentation Mass Spectra. Nat. Biotechnol. 2021, 39, 462– 471, DOI: 10.1038/s41587-020-0740-873https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXisVSlu7jK&md5=120b8fd8fe78db3c2623391833b3bd32Systematic classification of unknown metabolites using high-resolution fragmentation mass spectraDuehrkop, Kai; Nothias, Louis-Felix; Fleischauer, Markus; Reher, Raphael; Ludwig, Marcus; Hoffmann, Martin A.; Petras, Daniel; Gerwick, William H.; Rousu, Juho; Dorrestein, Pieter C.; Boecker, SebastianNature Biotechnology (2021), 39 (4), 462-471CODEN: NABIF9; ISSN:1087-0156. (Nature Portfolio)Metabolomics using nontargeted tandem mass spectrometry can detect thousands of mols. in a biol. sample. However, structural mol. annotation is limited to structures present in libraries or databases, restricting anal. and interpretation of exptl. data. Here we describe CANOPUS (class assignment and ontol. prediction using mass spectrometry), a computational tool for systematic compd. class annotation. CANOPUS uses a deep neural network to predict 2,497 compd. classes from fragmentation spectra, including all biol. relevant classes. CANOPUS explicitly targets compds. for which neither spectral nor structural ref. data are available and predicts classes lacking tandem mass spectrometry training data. In evaluation using ref. data, CANOPUS reached very high prediction performance (av. accuracy of 99.7% in cross-validation) and outperformed four baseline methods. We demonstrate the broad utility of CANOPUS by investigating the effect of microbial colonization in the mouse digestive system, through anal. of the chemodiversity of different Euphorbia plants and regarding the discovery of a marine natural product, revealing biol. insights at the compd. class level.
- 74van der Hooft, J. J. J.; Wandy, J.; Barrett, M. P.; Burgess, K. E. V.; Rogers, S. Topic modeling for untargeted substructure exploration in metabolomics. Proc. Natl. Acad. Sci. U.S.A. 2016, 113 (48), 13738– 13743, DOI: 10.1073/pnas.160804111374https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2snntlKntQ%253D%253D&md5=ac0b3c57ed44886cbc2d969522548e34Topic modeling for untargeted substructure exploration in metabolomicsvan der Hooft Justin Johan Jozias; Wandy Joe; Barrett Michael P; Burgess Karl E V; Rogers Simon; van der Hooft Justin Johan Jozias; Wandy Joe; Rogers Simon; Barrett Michael PProceedings of the National Academy of Sciences of the United States of America (2016), 113 (48), 13738-13743 ISSN:.The potential of untargeted metabolomics to answer important questions across the life sciences is hindered because of a paucity of computational tools that enable extraction of key biochemically relevant information. Available tools focus on using mass spectrometry fragmentation spectra to identify molecules whose behavior suggests they are relevant to the system under study. Unfortunately, fragmentation spectra cannot identify molecules in isolation but require authentic standards or databases of known fragmented molecules. Fragmentation spectra are, however, replete with information pertaining to the biochemical processes present, much of which is currently neglected. Here, we present an analytical workflow that exploits all fragmentation data from a given experiment to extract biochemically relevant features in an unsupervised manner. We demonstrate that an algorithm originally used for text mining, latent Dirichlet allocation, can be adapted to handle metabolomics datasets. Our approach extracts biochemically relevant molecular substructures ("Mass2Motifs") from spectra as sets of co-occurring molecular fragments and neutral losses. The analysis allows us to isolate molecular substructures, whose presence allows molecules to be grouped based on shared substructures regardless of classical spectral similarity. These substructures, in turn, support putative de novo structural annotation of molecules. Combining this spectral connectivity to orthogonal correlations (e.g., common abundance changes under system perturbation) significantly enhances our ability to provide mechanistic explanations for biological behavior.
- 75van Santen, J. A.; Jacob, G.; Singh, A. L.; Aniebok, V.; Balunas, M. J.; Bunsko, D.; Neto, F. C.; Castaño-Espriu, L.; Chang, C.; Clark, T. N.; Cleary Little, J. L.; Delgadillo, D. A.; Dorrestein, P. C.; Duncan, K. R.; Egan, J. M.; Galey, M. M.; Haeckl, F. P. J.; Hua, A.; Hughes, A. H.; Iskakova, D.; Khadilkar, A.; Lee, J.-H.; Lee, S.; LeGrow, N.; Liu, D. Y.; Macho, J. M.; McCaughey, C. S.; Medema, M. H.; Neupane, R. P.; O’Donnell, T. J.; Paula, J. S.; Sanchez, L. M.; Shaikh, A. F.; Soldatou, S.; Terlouw, B. R.; Tran, T. A.; Valentine, M.; van der Hooft, J. J. J.; Vo, D. A.; Wang, M.; Wilson, D.; Zink, K. E.; Linington, R. G. The Natural Products Atlas: An Open Access Knowledge Base for Microbial Natural Products Discovery. ACS Cent. Sci. 2019, 5 (11), 1824– 1833, DOI: 10.1021/acscentsci.9b0080675https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitFCit73P&md5=1ebc951ca96d93dd36d65dd8b3b3ad67The Natural Products Atlas: An Open Access Knowledge Base for Microbial Natural Products Discoveryvan Santen, Jeffrey A.; Jacob, Gregoire; Singh, Amrit Leen; Aniebok, Victor; Balunas, Marcy J.; Bunsko, Derek; Neto, Fausto Carnevale; Castano-Espriu, Laia; Chang, Chen; Clark, Trevor N.; Cleary Little, Jessica L.; Delgadillo, David A.; Dorrestein, Pieter C.; Duncan, Katherine R.; Egan, Joseph M.; Galey, Melissa M.; Haeckl, F. P. Jake; Hua, Alex; Hughes, Alison H.; Iskakova, Dasha; Khadilkar, Aswad; Lee, Jung-Ho; Lee, Sanghoon; LeGrow, Nicole; Liu, Dennis Y.; Macho, Jocelyn M.; McCaughey, Catherine S.; Medema, Marnix H.; Neupane, Ram P.; ODonnell, Timothy J.; Paula, Jasmine S.; Sanchez, Laura M.; Shaikh, Anam F.; Soldatou, Sylvia; Terlouw, Barbara R.; Tran, Tuan Anh; Valentine, Mercia; van der Hooft, Justin J. J.; Vo, Duy A.; Wang, Mingxun; Wilson, Darryl; Zink, Katherine E.; Linington, Roger G.ACS Central Science (2019), 5 (11), 1824-1833CODEN: ACSCII; ISSN:2374-7951. (American Chemical Society)Despite rapid evolution in the area of microbial natural products chem., there is currently no open access database contg. all microbially produced natural product structures. Lack of availability of these data is preventing the implementation of new technologies in natural products science. Specifically, development of new computational strategies for compd. characterization and identification are being hampered by the lack of a comprehensive database of known compds. against which to compare exptl. data. The creation of an open access, community-maintained database of microbial natural product structures would enable the development of new technologies in natural products discovery, and improve the interoperability of existing natural products data resources. However, these data are spread unevenly throughout the historical scientific literature, including both journal articles and international patents. These documents have no std. format, are often not digitized as machine readable text, and are not publicly available. Further, none of these documents have assocd. structure files (e.g., MOL, InChI, or SMILES), instead contg. images of structures. This makes extn. and formatting of relevant natural products data a formidable challenge. Using a combination of manual curation and automated data mining approaches we have created a database of microbial natural products (The Natural Products Atlas, www.npatlas.org) that includes 24,594 compds. and contains referenced data for structure, compd. names, source organisms, isolation refs., total syntheses and instances of structural reassignment. This database is accompanied by an interactive web portal that permits searching by structure, substructure, and phys. properties. The Web site also provides mechanisms for visualizing natural products chem. space, and dashboards for displaying author and discovery timeline data. These interactive tools offer a powerful knowledge base for natural products discovery with a central interface for structure and property-based searching, and presents new viewpoints on structural diversity in natural products. The Natural Products Atlas has been developed under FAIR principles (Findable, Accessible, Interoperable, and Reusable) and is integrated with other emerging natural product databases, including the Min. Information About a Biosynthetic Gene Cluster (MIBiG) repository, and the Global Natural Products Social Mol. Networking (GNPS) platform. It is designed as a community-supported resource to provide a central repository for known natural product structures from microorganisms, and is the 1st comprehensive, open access resource of this type. It is expected that the Natural Products Atlas will enable the development of new natural products discovery modalities and accelerate the process of structural characterization for complex natural products libraries. The Natural Products Atlas is a new online database of microbially derived natural product structures, designed as a comprehensive open access repository for the scientific community.
- 76MarinLit. A Database of the Marine Natural Products Literature, Royal Society of Chemistry http://pubs.rsc.org/marinlit/. (accessed January 20, 2023).There is no corresponding record for this reference.
- 77Al Shaer, D.; Al Musaimi, O.; de la Torre, B. G.; Albericio, F. Hydroxamate siderophores: Natural occurrence, chemical synthesis, iron binding affinity and use as Trojan horses against pathogens. Eur. J. Med. Chem. 2020, 208, 112791 DOI: 10.1016/j.ejmech.2020.11279177https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVynurfI&md5=5ac6f84332f643caede5b195cef1b835Hydroxamate siderophores: Natural occurrence, chemical synthesis, iron binding affinity and use as Trojan horses against pathogensAl Shaer, Danah; Al Musaimi, Othman; de la Torre, Beatriz G.; Albericio, FernandoEuropean Journal of Medicinal Chemistry (2020), 208 (), 112791CODEN: EJMCA5; ISSN:0223-5234. (Elsevier Masson SAS)A review. Hydroxamic acids are an important class of mols., in particular because of their metal-chelating ability. Microorganisms, including pathogenic bacteria, use hydroxamate-based entities (siderophores), among others, to acquire Fe (III). The "Trojan horse" strategy exploits the need of bacteria for this metal by using Fe (III) active transporters to carry antibacterial or bactericidal moieties into the bacterial cell. Many natural Trojan horses (sideromycins) are derived from hydroxamic acids, thereby reflecting their potency. Various artificial sideromycins and their antibacterial activities have been reported. This review discusses the structural aspects of the hydroxamate-siderophores isolated in the last two decades, the chem. synthesis of their building blocks, their binding affinity towards Fe (III), and their application as Trojan horses (weaknesses and strengths).
- 78Martinez, J. S.; Carter-Franklin, J. N.; Mann, E. L.; Martin, J. D.; Haygood, M. G.; Butler, A. Structure and membrane affinity of a suite of amphiphilic siderophores produced by a marine bacterium. Proc. Natl. Acad. Sci. U.S.A. 2003, 100 (7), 3754– 3759, DOI: 10.1073/pnas.063744410078https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXivFSqsbs%253D&md5=f97cddc20add56b20664316273764d9eStructure and membrane affinity of a suite of amphiphilic siderophores produced by a marine bacteriumMartinez, Jennifer S.; Carter-Franklin, Jayme N.; Mann, Elizabeth L.; Martin, Jessica D.; Haygood, Margo G.; Butler, AlisonProceedings of the National Academy of Sciences of the United States of America (2003), 100 (7), 3754-3759CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Iron concns. in the ocean are low enough to limit the growth of marine microorganisms, which raises questions about the mol. mechanisms these organisms use to acquire iron. Marine bacteria have been shown to produce siderophores to facilitate iron(III) uptake. We describe the structures of a suite of amphiphilic siderophores, named the amphibactins, which are produced by a nearshore isolate, γ Proteobacterium, Vibrio sp. R-10. Each amphibactin has the same Tris-hydroxamate-contg. peptidic headgroup composed of three ornithine residues and one serine residue but differs in the acyl appendage, which ranges from C-14 to C-18 and varies in the degree of satn. and hydroxylation. Although amphiphilic siderophores are relatively rare, cell-assocd. amphiphilic siderophores are even less common. We find that the amphibactins are cell-assocd. siderophores. As a result of the variation in the nature of the fatty acid appendage and the cellular location of the amphibactins, the membrane partitioning of these siderophores was investigated. The physiol. mixt. of amphibactins had a range of membrane affinities (3.8 × 103 to 8.3 × 102 M-1) that are larger overall than other amphiphilic siderophores, likely accounting for their cell assocn. This cell assocn. is likely an important defense against siderophore diffusion in the oceanic environment. The phylogenetic affiliation of Vibrio sp. R-10 is discussed, as well as the obsd. predominance of amphiphilic siderophores produced by marine bacteria in contrast to those produced by terrestrial bacteria.
- 79Walker, L. R.; Tfaily, M. M.; Shaw, J. B.; Hess, N. J.; Paša-Tolić, L.; Koppenaal, D. W. Unambiguous identification and discovery of bacterial siderophores by direct injection 21 T Fourier transform ion cyclotron resonance mass spectrometry. Metallomics 2017, 9 (1), 82– 92, DOI: 10.1039/C6MT00201C79https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitVWqu77I&md5=2ddad7a08c033090c4bad1037b8c9c14Unambiguous identification and discovery of bacterial siderophores by direct injection 21 Tesla Fourier transform ion cyclotron resonance mass spectrometryWalker, Lawrence R.; Tfaily, Malak M.; Shaw, Jared B.; Hess, Nancy J.; Pasa-Tolic, Ljiljana; Koppenaal, David W.Metallomics (2017), 9 (1), 82-92CODEN: METAJS; ISSN:1756-591X. (Royal Society of Chemistry)Under iron-limiting conditions, bacteria produce low mol. mass Fe(iii) binding mols. known as siderophores to sequester the Fe(iii), along with other elements, increasing their bioavailability. Siderophores are thought to influence iron cycling and biogeochem. in both marine and terrestrial ecosystems and hence the need for rapid, confident characterization of these compds. has increased. In this study, the type of siderophores produced by two marine bacterial species, Synechococcus sp. PCC 7002 and Vibrio cyclitrophicus 1F53, were characterized by use of a newly developed 21 T Fourier-transform ion cyclotron resonance mass spectrometer (FTICR MS) with direct injection electrospray ionization. This technique allowed for the rapid detection of synechobactins from Synechococcus sp. PCC 7002 as well as amphibactins from Vibrio cyclitrophicus 1F53 based on high mass accuracy and resoln. allowing for observation of specific Fe isotopes and isotopic fine structure enabling highly confident identification of these siderophores. When combined with mol. network anal. two new amphibactins were discovered and verified by tandem MS. These results show that high-field FTICR MS is a powerful technique that will greatly improve the ability to rapidly identify and discover metal binding species in the environment.
- 80Pérez-Miranda, S.; Cabirol, N.; George-Téllez, R.; Zamudio-Rivera, L. S.; Fernández, F. J. O-CAS, a fast and universal method for siderophore detection. J. Microbiol. Methods 2007, 70 (1), 127– 131, DOI: 10.1016/j.mimet.2007.03.02380https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXmvVKmu74%253D&md5=70124c1ff07c8c607680221459c41b97O-CAS, a fast and universal method for siderophore detectionPerez-Miranda, S.; Cabirol, N.; George-Tellez, R.; Zamudio-Rivera, L. S.; Fernandez, F. J.Journal of Microbiological Methods (2007), 70 (1), 127-131CODEN: JMIMDQ; ISSN:0167-7012. (Elsevier B.V.)In this work, the popular CAS assay for siderophore detection, based on the utilization of chrome azurol S, was redesigned and optimized to produce a new, fast, non-toxic, and easy method to det. a wide variety of microorganisms capable of siderophore prodn. on a solid medium. Furthermore, this specific bioassay allows for the identification of more than one single siderophore-producing microorganism at the same time, using an overlay technique in which a modified CAS medium is cast upon culture agar plates (thus its name "O-CAS", for overlaid CAS). Detection was optimized through adjustments to the medium's compn. and a quantifying strategy. Specificity of the bioassay was tested on microorganisms known for siderophore prodn. As a result, a total of 48 microorganisms were isolated from three different types of samples (fresh water, salt water, and alk. soil), of which 36 were detd. as siderophore producers. The compds. identified through this method belonged to both hydroxamate and catechol-types, previously reported to cause color change of the CAS medium from blue to orange and purple, resp. Some isolated microorganisms, however, caused a color change that differed from previous descriptions.
- 81Raines, D. J.; Sanderson, T. J.; Wilde, E. J.; Duhme-Klair, A. K. Siderophores. In Reference Module in Chemistry, Molecular Sciences and Chemical Engineering; Elsevier, 2015.There is no corresponding record for this reference.
- 82Hou, Z.; Raymond, K. N.; O’Sulliva, B.; Esker, T. W.; Nishio, T. A Preorganized Siderophore: Thermodynamic and Structural Characterization of Alcaligin and Bisucaberin, Microbial Macrocyclic Dihydroxamate Chelating Agents1. Inorg. Chem. 1998, 37 (26), 6630– 6637, DOI: 10.1021/ic981018282https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXnsFKnsL4%253D&md5=29e4130272fe191f38587469c4980b9dA Preorganized Siderophore: Thermodynamic and Structural Characterization of Alcaligin and Bisucaberin, Microbial Macrocyclic Dihydroxamate Chelating AgentsHou, Zhiguo; Raymond, Kenneth N.; O'Sullivan, Brendon; Esker, Todd W.; Nishio, TakayukiInorganic Chemistry (1998), 37 (26), 6630-6637CODEN: INOCAJ; ISSN:0020-1669. (American Chemical Society)The Fe coordination chem. of two macrocyclic dihydroxamate siderophores, alcaligin (AG) and bisucaberin (BR), was studied thermodynamically and structurally. Alcaligin is a siderophore of freshwater bacteria as well as mammalian pathogens, including the bacterium that causes whooping cough in humans, while bisucaberin, a structural analog of alcaligin, is produced by marine bacteria. Both alcaligin and bisucaberin form 1:1 ferric complexes (FeL+) in acidic conditions and 2:3 ferric complexes (Fe2L3) at and above neutral pH. The stability consts. of these macrocyclic dihydroxamate siderophores differ significantly from that of rhodotorulic acid (RA), a linear dihydroxamate siderophore. Notably, KFeL of alcaligin is 32 times greater than that of rhodotorulic acid, while the subsequent stepwise formation const. for Fe2L3 is 3 times less. The Fe(III) complexes of alcaligin are stereospecific; the abs. configuration of the Fe2L3 complex (CD and x-ray structure) is Λ. The structure of the Fe2L3 alcaligin complex is a topol. alternative to the triple-helicate structure of the rhodotorulic complex Fe2(RA)3. The structures of the free ligand and the bisbidentate ligand in the FeL complex are essentially identical, indicating that alcaligin is highly preorganized for metal ion binding. This explains the difference in KFeL between alcaligin and rhodotorulic acid, as well as explaining the monobridged topol. of the Fe2L3 alcaligin complex. The protonation consts. (log Ka1 and log Ka2) are 9.42(5) and 8.61(1) for alcaligin and 9.49(2) and 8.76(3) for bisucaberin. The stepwise formation consts. of the Fe(III) complexes (log KML and log KM2L3) are 23.5(2) and 17.7(2) for alcaligin and 23.5(5) and 17.2(5) for bisucaberin. The overall formation consts. (log β230) of alcaligin and bisucaberin are 64.7(1) and 64.3(1). The soln. chem. of Fe(III) and alcaligin was further studied at a lower ligand to metal ratio (1:1). At high pH, a novel 2:2 ferric bis-μ-oxo-bridged complex of alcaligin forms (Fe2L2O22-) with a log β22-4 of 16.7(2). This species exhibits behavior consistent with an Fe bis-μ-oxo complex, including antiferromagnetic coupling. Fe2(AG)3·25H2O crystallizes in the orthorhombic space group P212121 with a 13.3374(4), b 16.1879(5), c 37.886(1) Å, V = 8179.7(4), Z = 4, final R (Rw) = 0.053(0.068).
- 83Harris, W. R.; Carrano, C. J.; Raymond, K. N. Coordination chemistry of microbial iron transport compounds. 16. Isolation, characterization, and formation constants of ferric aerobactin. J. Am. Chem. Soc. 1979, 101 (10), 2722– 2727, DOI: 10.1021/ja00504a03883https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE1MXkvVGrsbg%253D&md5=5fffdb06f632741d94b80c99eb5331c7Coordination chemistry of microbial iron transport compounds. 16. Isolation, characterization, and formation constants of ferric aerobactinHarris, Wesley R.; Carrano, Carl J.; Raymond, Kenneth N.Journal of the American Chemical Society (1979), 101 (10), 2722-7CODEN: JACSAT; ISSN:0002-7863.Aerobactin, a dihydroxamate deriv. of citric acid, is a siderophore produced by Aerobacter aerogenes. The Fe complex was isolated from neutral aq. solns. as the trisodium salt. The high-spin octahedral complex was formed using the 2 bidentate hydroxamate groups and the central carboxylate and hydroxyl moieties of the citrate backbone. Ferric aerobactin exists predominantly as the Λ optical isomer in aq. solns. The stability consts. (logβ113 = 31.74, log β112 = 29.70, log β111 = 26.68, log β110 = 23.06, logβ11‾1 = 18.48) and redox potential also were detd. from spectroscopic, potentiometric titrn., and electrochem. techniques. The implication of these results to the mechanism of Fe uptake and release by A. aerogenes is discussed.
- 84Ito, T.; Neilands, J. B. Products of “Low-iron Fermentation” with Bacillus subilis: Isolation, Characterization and Synthesis of 2,3-Dihydroxybenzoylglycine1,2. J. Am. Chem. Soc. 1958, 80 (17), 4645– 4647, DOI: 10.1021/ja01550a05884https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaG1MXivFeqsA%253D%253D&md5=0cce30ee41e36a134f885e500f9d95edProducts of low-iron fermentation with Bacillus subtilis: isolation, characterization, and synthesis of 2,3-dihydroxybenzoylglycineIto, Takeru; Neilands, J. B.Journal of the American Chemical Society (1958), 80 (), 4645-7CODEN: JACSAT; ISSN:0002-7863.cf. C.A. 51, 14004i. The phenolic acid produced by B. subtilis NRRL B-1471 in Fe deficiency was crystd. and identified by synthesis as 2,3-dihydroxybenzoylglycine (I); synthetic I was indistinguishable from natural I by paper chromatography in various systems, color reactions with FeCl3, reaction with HNO2, soly., ultraviolet spectrum, infrared spectrum, apparent pKa values, and mol. wt. 2,3-(HO)2C6H3CO2H (1 g.) and 0.7-0.8 g. glycine Et ester in 5-6 ml. tetrahydrofuran (THF) treated with 1.5 g. dicyclohexylcarbodiimide in 3-5 ml. THF, the mixt. held overnight at room temp. under N, a small amt. of AcOH added, the soln. filtered, the solvent evapd., the residue dissolved in EtOAc, washed with dil. HCl, the EtOAc evapd., the residue stirred 4 hrs. at room temp. under N in 20-30 ml. N NaOH, filtered, the filtrate acidified with 4-6 ml. dil. H2SO4, extd. with EtOAc, the solvent evapd. to dryness, and the residue in dil. NH4OH treated (ice bath) with dil. HCl yielded 500 mg. I, m. 210-11°.
- 85Barghouthi, S.; Young, R.; Olson, M. O.; Arceneaux, J. E.; Clem, L. W.; Byers, B. R. Amonabactin, a novel tryptophan- or phenylalanine-containing phenolate siderophore in Aeromonas hydrophila. J. Bacteriol. 1989, 171 (4), 1811– 1816, DOI: 10.1128/jb.171.4.1811-1816.1989There is no corresponding record for this reference.
- 86Atkin, C. L.; Neilands, J. B. Rhodotorulic acid, a diketopiperazine dihydroxamic acid with growth-factor activity. I. Isolation and characterization. Biochemistry 1968, 7 (10), 3734– 3739, DOI: 10.1021/bi00850a05486https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF1MXhtVSn&md5=52982880fd8eae737b0cd9aaaeff7af9Rhodotorulic acid, a diketopiperazine dihydroxamic acid with growth-factor activity. I. Isolation and characterizationAtkin, Curtis L.; Neilands, J. B.Biochemistry (1968), 7 (10), 3734-9CODEN: BICHAW; ISSN:0006-2960.A strongly Fe(III)-binding compd. with the properties of a secondary hydroxamic acid was isolated from supernatants of Fe-deficient cultures of a red yeast, subsequently identified as Rhodotorula pilimaniae. The name rhodotorulic acid was selected inasmuch as a no. of Rhodotorula species produce the compound in low Fe media. It was characterized by degradation, spectral properties, and synthetic expts. as LL-3,6-bis(N-acetyl-3-hydroxyaminopropyl)-2,5-piperazinedione, i.e., the diketopiperazine of δ-N-acetyl-L-δ-N-hydroxyornithine, which amino acid is a constituent of ferrichromes, albomycins, and fusarinines. The analogous diketopiperazine of δ-N-acetyl-L-ornithine was identical with a redn. product of rhodotorulic acid. Rhodotorulic acid has biol. activity comparable with that of schizokinen in Lankford's Bacillus test system (Byers, et al., 1967). It also shows potent growth-factor activity in assays with Arthrobacter species, although lacking the antagonistic effect of other sideramine growth factors on albomycin inhibition of bacterial growth.
- 87Spasojević, I.; Boukhalfa, H.; Stevens, R. D.; Crumbliss, A. L. Aqueous Solution Speciation of Fe(III) Complexes with Dihydroxamate Siderophores Alcaligin and Rhodotorulic Acid and Synthetic Analogues Using Electrospray Ionization Mass Spectrometry. Inorg. Chem. 2001, 40 (1), 49– 58, DOI: 10.1021/ic991390xThere is no corresponding record for this reference.
- 88Xu, G.; Martinez, J. S.; Groves, J. T.; Butler, A. Membrane Affinity of the Amphiphilic Marinobactin Siderophores. J. Am. Chem. Soc. 2002, 124 (45), 13408– 13415, DOI: 10.1021/ja026768w88https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XotVegtrg%253D&md5=a0dde8ef0fbecc71e02ec4fd10f668baMembrane Affinity of the Amphiphilic Marinobactin SiderophoresXu, Guofeng; Martinez, Jennifer S.; Groves, John T.; Butler, AlisonJournal of the American Chemical Society (2002), 124 (45), 13408-13415CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Marinobactins are a class of newly discovered marine bacterial siderophores with a unique amphiphilic structure, suggesting that their functions relate to interactions with cell membranes. Here we use small and large unilamellar L-α-dimyristoylphosphatidylcholine vesicles (SUVs and LUVs) as model membranes to examine the thermodn. and kinetics of the membrane binding of marinobactins, particularly marinobactin E (apo-ME) and its iron(III) complex, Fe-ME. Siderophore-membrane interactions are characterized by NMR line broadening, stopped-flow spectrophotometry, fluorescence quenching, and ultracentrifugation. It is detd. that apo-ME has a strong affinity for lipid membranes with molar fraction partition coeffs. Kxapo-ME = 6.3×105 for SUVs and 3.6×105 for LUVs. This membrane assocn. is shown to cause only a 2-fold decrease in the rate of iron(III) binding by apo-ME. However, upon the formation of the iron(III) complex Fe-ME, the membrane affinity of the siderophore decreased substantially (KxFe-ME = 1.3×104 for SUVs and 9.6×103 for LUVs). The kinetics of membrane binding and dissocn. by Fe-ME were also detd. (konFe-ME = 1.01 M-1 s-1; koffFe-ME = 4.4×10-3 s-1). The suite of marinobactins with different fatty acid chain lengths and degrees of chain unsatn. showed a range of membrane affinities (5.8×103 to 36 M-1). The affinity that marinobactins exhibit for membranes and the changes obsd. upon iron binding could provide unique biol. advantages in a receptor-assisted iron acquisition process in which loss of the iron-free siderophore by diffusion is limited by the strong assocn. with the lipid phase.
- 89Harrington, J. M.; Crumbliss, A. L. The redox hypothesis in siderophore-mediated iron uptake. BioMetals 2009, 22 (4), 679– 689, DOI: 10.1007/s10534-009-9233-489https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXotFCisrs%253D&md5=bd753fb87d6736aa7ca07f39afc3ca45The redox hypothesis in siderophore-mediated iron uptakeHarrington, James M.; Crumbliss, Alvin L.BioMetals (2009), 22 (4), 679-689CODEN: BOMEEH; ISSN:0966-0844. (Springer)A review. The viability of iron(III/II) redn. as the initial step in the in vivo release of iron from its thermodynamically stable siderophore complex is explored.
- 90Schalk, I. J.; Guillon, L. Fate of ferrisiderophores after import across bacterial outer membranes: different iron release strategies are observed in the cytoplasm or periplasm depending on the siderophore pathways. Amino Acids 2013, 44 (5), 1267– 1277, DOI: 10.1007/s00726-013-1468-290https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXlvVCis7w%253D&md5=14a340b3a3a5fa9b8f9d775da504a4b1Fate of ferrisiderophores after import across bacterial outer membranes: different iron release strategies are observed in the cytoplasm or periplasm depending on the siderophore pathwaysSchalk, Isabelle J.; Guillon, LaurentAmino Acids (2013), 44 (5), 1267-1277CODEN: AACIE6; ISSN:0939-4451. (SpringerWienNewYork)A review. Siderophore prodn. and utilization is one of the major strategies deployed by bacteria to get access to iron, a key nutrient for bacterial growth. The biol. function of siderophores is to solubilize iron in the bacterial environment and to shuttle it back to the cytoplasm of the microorganisms. This uptake process for Gram-neg. species involves TonB-dependent transporters for translocation across the outer membranes. In Escherichia coli and many other Gram-neg. bacteria, ABC transporters assocd. with periplasmic binding proteins import ferrisiderophores across cytoplasmic membranes. Recent data reveal that in some siderophore pathways, this step can also be carried out by proton-motive force-dependent permeases, for example the ferrichrome and ferripyochelin pathways in Pseudomonas aeruginosa. Iron is then released from the siderophores in the bacterial cytoplasm by different enzymic mechanisms depending on the nature of the siderophore. Another strategy has been reported for the pyoverdine pathway in P. aeruginosa: iron is released from the siderophore in the periplasm and only siderophore-free iron is transported into the cytoplasm by an ABC transporter having two atypical periplasmic binding proteins. This review presents recent findings concerning both ferrisiderophore and siderophore-free iron transport across bacterial cytoplasmic membranes and considers current knowledge about the mechanisms involved in iron release from siderophores.
- 91Miethke, M.; Marahiel, M. A. Siderophore-Based Iron Acquisition and Pathogen Control. Microbiol. Mol. Biol. Rev. 2007, 71 (3), 413– 451, DOI: 10.1128/MMBR.00012-0791Siderophore-based iron acquisition and pathogen controlMiethke, Marcus; Marahiel, Mohamed A.Microbiology and Molecular Biology Reviews (2007), 71 (3), 413-451CODEN: MMBRF7; ISSN:1092-2172. (American Society for Microbiology)A review. High-affinity iron acquisition is mediated by siderophore-dependent pathways in the majority of pathogenic and nonpathogenic bacteria and fungi. Considerable progress has been made in characterizing and understanding mechanisms of siderophore synthesis, secretion, iron scavenging, and siderophore-delivered iron uptake and its release. The regulation of siderophore pathways reveals multilayer networks at the transcriptional and posttranscriptional levels. Due to the key role of many siderophores during virulence, coevolution led to sophisticated strategies of siderophore neutralization by mammals and (re)utilization by bacterial pathogens. Surprisingly, hosts also developed essential siderophore-based iron delivery and cell conversion pathways, which are of interest for diagnostic and therapeutic studies. In the last decades, natural and synthetic compds. have gained attention as potential therapeutics for iron-dependent treatment of infections and further diseases. Promising results for pathogen inhibition were obtained with various siderophore-antibiotic conjugates acting as "Trojan horse" toxins and siderophore pathway inhibitors. In this article, general aspects of siderophore-mediated