Fermentative Indole Production via Bacterial Tryptophan Synthase Alpha Subunit and Plant Indole-3-Glycerol Phosphate Lyase Enzymes

Click to copy article linkArticle link copied!

This article references 55 other publications.

1. 1

   Ma, Q.; Zhang, X.; Qu, Y. Biodegradation and Biotransformation of Indole: Advances and Perspectives. Front. Microbiol. 2018, 9, 2625  DOI: 10.3389/FMICB.2018.02625

   Google Scholar

   1

   Biodegradation and Biotransformation of Indole: Advances and Perspectives

   Ma Qiao; Zhang Xuwang; Qu Yuanyuan

   Frontiers in microbiology (2018), 9 (), 2625 ISSN:1664-302X.

   Indole is long regarded as a typical N-heterocyclic aromatic pollutant in industrial and agricultural wastewater, and recently it has been identified as a versatile signaling molecule with wide environmental distributions. An exponentially growing number of researches have been reported on indole due to its significant roles in bacterial physiology, pathogenesis, animal behavior and human diseases. From the viewpoint of both environmental bioremediation and biological studies, the researches on metabolism and fates of indole are important to realize environmental treatment and illuminate its biological function. Indole can be produced from tryptophan by tryptophanase in many bacterial species. Meanwhile, various bacterial strains have obtained the ability to transform and degrade indole. The characteristics and pathways for indole degradation have been investigated for a century, and the functional genes for indole aerobic degradation have also been uncovered recently. Interestingly, many oxygenases have proven to be able to oxidize indole to indigo, and this historic and motivating case for biological applications has attracted intensive attention for decades. Herein, the bacteria, enzymes and pathways for indole production, biodegradation and biotransformation are systematically summarized, and the future researches on indole-microbe interactions are also prospected.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3crhsVyqtA%253D%253D&md5=6c327293e0af8ba37580c4b2cfd70699
2. 2

   Lee, J.-H.; Wood, T. K.; Lee, J. Roles of Indole as an Interspecies and Interkingdom Signaling Molecule. Trends Microbiol. 2015, 23, 707– 718,  DOI: 10.1016/j.tim.2015.08.001

   Google Scholar

   2

   Roles of Indole as an Interspecies and Interkingdom Signaling Molecule

   Lee, Jin-Hyung; Wood, Thomas K.; Lee, Jintae

   Trends in Microbiology (2015), 23 (11), 707-718CODEN: TRMIEA; ISSN:0966-842X. (Elsevier Ltd.)

   A review. A no. of bacteria, and some plants, produce large quantities of indole, which is widespread in animal intestinal tracts and in the rhizosphere. Indole, as an interspecies and interkingdom signaling mol., plays important roles in bacterial pathogenesis and eukaryotic immunity. Furthermore, indole and its derivs. are viewed as potential antivirulence compds. against antibiotic-resistant pathogens because of their ability to inhibit quorum sensing and virulence factor prodn. Indole modulates oxidative stress, intestinal inflammation, and hormone secretion in animals, and it controls plant defense systems and growth. Insects and nematodes can recognize indole, which controls some of their behavior. This review presents current knowledge regarding indole and its derivs., their biotechnol. applications and their role in prokaryotic and eukaryotic systems.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhs1SltbjP&md5=d6cbeb6c056bef55ff8e4f9ff7eaf6f4
3. 3

   Zarkan, A.; Liu, J.; Matuszewska, M.; Gaimster, H.; Summers, D. K. Local and Universal Action: The Paradoxes of Indole Signalling in Bacteria. Trends Microbiol. 2020, 28, 566– 577,  DOI: 10.1016/j.tim.2020.02.007

   Google Scholar

   3

   Local and Universal Action: The Paradoxes of Indole Signalling in Bacteria

   Zarkan, Ashraf; Liu, Junyan; Matuszewska, Marta; Gaimster, Hannah; Summers, David K.

   Trends in Microbiology (2020), 28 (7), 566-577CODEN: TRMIEA; ISSN:0966-842X. (Elsevier Ltd.)

   A review. Indole is a signaling mol. produced by many bacterial species and involved in intraspecies, interspecies, and interkingdom signaling. Despite the increasing vol. of research published in this area, many aspects of indole signaling remain enigmatic. There is disagreement over the mechanism of indole import and export and no clearly defined target through which its effects are exerted. Progress is hindered further by the confused and sometimes contradictory body of indole research literature. We explore the reasons behind this lack of consistency and speculate whether the discovery of a new, pulse mode of indole signaling, together with a move away from the idea of a conventional protein target, might help to overcome these problems and enable the field to move forward.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXkslahsbo%253D&md5=c6ea75a69269d6b5f83e9fb7c56c5ed3
4. 4

   Frey, M.; Stettner, C.; Paré, P. W.; Schmelz, E. A.; Tumlinson, J. H.; Gierl, A. An Herbivore Elicitor Activates the Gene for Indole Emission in Maize. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 14801– 14806,  DOI: 10.1073/PNAS.260499897

   Google Scholar

   4

   An herbivore elicitor activates the gene for indole emission in maize

   Frey, Monika; Stettner, Cornelia; Pare, Paul W.; Schmelz, Eric A.; Tumlinson, James H.; Gierl, Alfons

   Proceedings of the National Academy of Sciences of the United States of America (2000), 97 (26), 14801-14806CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)

   Maize and a variety of other plant species release volatile compds. in response to herbivore attack that serve as chem. cues to signal natural enemies of the feeding herbivore. N-(17-hydroxylinolenoyl)-L-glutamine is an elicitor component that has been isolated and chem. characterized from the regurgitant of the herbivore-pest beet armyworm. This fatty acid deriv., referred to as volicitin, triggers the synthesis and release of volatile components, including terpenoids and indole in maize. Here we report on a previously unidentified enzyme, indole-3-glycerol phosphate lyase (IGL), that catalyzes the formation of free indole and is selectively activated by volicitin. IGL's enzymic properties are similar to BX1, a maize enzyme that serves as the entry point to the secondary defense metabolites DIBOA and DIMBOA. Gene-sequence anal. indicates that Igl and Bx1 are evolutionarily related to the tryptophan synthase alpha subunit.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXitVGnug%253D%253D&md5=0589981013df443902f15bc3360d5328
5. 5

   Erb, M.; Veyrat, N.; Robert, C. A. M.; Xu, H.; Frey, M.; Ton, J.; Turlings, T. C. J. Indole is an Essential Herbivore-Induced Volatile Priming Signal in Maize. Nat. Commun. 2015, 6, 6273  DOI: 10.1038/ncomms7273

   Google Scholar

   5

   Indole is an essential herbivore-induced volatile priming signal in maize

   Erb, Matthias; Veyrat, Nathalie; Robert, Christelle A. M.; Xu, Hao; Frey, Monika; Ton, Jurriaan; Turlings, Ted C. J.

   Nature Communications (2015), 6 (), 6273CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)

   Herbivore-induced volatile org. compds. prime non-attacked plant tissues to respond more strongly to subsequent attacks. However, the key volatiles that trigger this primed state remain largely unidentified. In maize, the release of the arom. compd. indole is herbivore-specific and occurs earlier than other induced responses. We therefore hypothesized that indole may be involved in airborne priming. Using indole-deficient mutants and synthetic indole dispensers, we show that herbivore-induced indole enhances the induction of defensive volatiles in neighboring maize plants in a species-specific manner. Furthermore, the release of indole is essential for priming of mono- and homoterpenes in systemic leaves of attacked plants. Indole exposure markedly increases the herbivore-induced prodn. of the stress hormones jasmonate-isoleucine conjugate and abscisic acid, which represents a likely mechanism for indole-dependent priming. These results demonstrate that indole functions as a rapid and potent aerial priming agent that preps. systemic tissues and neighboring plants for incoming attacks.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXosFemsrk%253D&md5=5c7a15282d694d5099591342e3cdc8c4
6. 6

   Frey, M.; Chomet, P.; Glawischnig, E.; Stettner, C.; Grün, S.; Winklmair, A.; Eisenreich, W.; Bacher, A.; Meeley, R. B.; Briggs, S. P.; Simcox, K.; Gierl, A. Analysis of a Chemical Plant Defense Mechanism in Grasses. Science 1997, 277, 696– 699,  DOI: 10.1126/SCIENCE.277.5326.696

   Google Scholar

   6

   Analysis of a chemical plant defense mechanism in grasses

   Frey, Monika; Chomet, Paul; Glawischnig, Erich; Stettner, Cornelia; Grun, Sebastian; Winklmair, Albert; Eisenreich, Wolfgang; Bacher, Adelbert; Meeley, Robert B.; Briggs, Steven P.; Simcox, Kevin; Gierl, Alfons

   Science (Washington, D. C.) (1997), 277 (5326), 696-699CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)

   In the Gramineae, the cyclic hydroxamic acids 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) and 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOOA) from part of the defense against insects and microbial pathogens. Five genes, Bx1 through Bx5, are required for DIBOA biosynthesis in maize. The functions of these five genes, clustered on chromosome 4, were demonstrated in vitro. Bx1 encodes a tryptophan synthase α homolog that catalyzes the formation of indole for the prodn. of secondary metabolites rather than tryptophan, thereby defining the branch point from primary to secondary metab. Bx2 through Bx5 encode cytochrome P 450-dependent monooxygenases that catalyze four consecutive hydroxylations and one ring expansion to form the highly oxidized DIBOA.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXltVSlu70%253D&md5=28414ccc829b1f766f3c69e80e3074d9
7. 7

   Jin, Z.; Kim, J.-H.; Park, S. U.; Kim, S.-U. Cloning and Characterization of Indole Synthase (INS) and a Putative Tryptophan Synthase α-subunit (TSA) Genes from Polygonum tinctorium. Plant Cell Rep. 2016, 35, 2449– 2459,  DOI: 10.1007/s00299-016-2046-3

   Google Scholar

   7

   Cloning and characterization of indole synthase (INS) and a putative tryptophan synthase α-subunit (TSA) genes from Polygonum tinctorium

   Jin, Zhehao; Kim, Jin-Hee; Park, Sang Un; Kim, Soo-Un

   Plant Cell Reports (2016), 35 (12), 2449-2459CODEN: PCRPD8; ISSN:0721-7714. (Springer)

   Key message: Two cDNAs for indole-3-glycerol phosphate lyase homolog were cloned from Polygonum tinctorium. One encoded cytosolic indole synthase possibly in indigoid synthesis, whereas the other encoded a putative tryptophan synthase α-subunit. Abstr.: Indigo is an old natural blue dye produced by plants such as Polygonum tinctorium. A key step in plant indigoid biosynthesis is prodn. of indole by indole-3-glycerol phosphate lyase (IGL). Two tryptophan synthase α-subunit (TSA) homologs, PtIGL-short and -long, were isolated by RACE PCR from P. tinctorium. The genome of the plant contained two genes coding for IGL. The short and the long forms, resp., encoded 273 and 316 amino acid residue-long proteins. The short form complemented E. coli ΔtnaA ΔtrpA mutant on tryptophan-depleted agar plate signifying prodn. of free indole, and thus was named indole synthase gene (PtINS). The long form, either intact or without the transit peptide sequence, did not complement the mutant and was tentatively named PtTSA. PtTSA was delivered into chloroplast as predicted by 42-residue-long targeting sequence, whereas PtINS was localized in cytosol. Genomic structure anal. suggested that a TSA duplicate acquired splicing sites during the course of evolution toward PtINS so that the targeting sequence-contg. pre-mRNA segment was deleted as an intron. PtINS had about 2-5-folds higher transcript level than that of PtTSA, and treatment of 2,1,3-benzothiadiazole caused the relative transcript level of PtINS over PtTSA was significantly enhanced in the plant. The results indicate participation of PtINS in indigoid prodn.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsVCmsbrF&md5=92fe98faed812b596f728db2c1316978
8. 8

   Zhuang, X.; Fiesselmann, A.; Zhao, N.; Chen, H.; Frey, M.; Chen, F. Biosynthesis and Emission of Insect Herbivory-induced Volatile Indole in Rice. Phytochemistry 2012, 73, 15– 22,  DOI: 10.1016/j.phytochem.2011.08.029

   Google Scholar

   8

   Biosynthesis and emission of insect herbivory-induced volatile indole in rice

   Zhuang, Xiaofeng; Fiesselmann, Andreas; Zhao, Nan; Chen, Hao; Frey, Monika; Chen, Feng

   Phytochemistry (Elsevier) (2012), 73 (), 15-22CODEN: PYTCAS; ISSN:0031-9422. (Elsevier Ltd.)

   Insect-damaged rice plants emit a complex mixt. of volatiles that are highly attractive to parasitic wasps. Indole is one constituent of insect-induced rice volatiles, and is produced in plants by the enzyme indole-3-glycerol phosphate lyase (IGL). The alpha-subunit of tryptophan synthase (TSA) is the IGL that catalyzes the conversion of indole-3-glycerol phosphate to indole in the alpha-reaction of tryptophan synthesis; however, TSA is only active in the complex with the beta-subunit of tryptophan synthase and is not capable of producing free indole. In maize a TSA homolog, ZmIgl, is the structural gene responsible for volatile indole biosynthesis. Bioinformatic anal. based on the ZmIgl-sequence indicated that the rice genome contains five homologous genes. Three homologs Os03g58260, Os03g58300 and Os07g08430, have detectable transcript levels in seedling tissue and were expressed in both insect-damaged and control rice plants. Only Os03g58300, however, was up-regulated by insect feeding. Recombinant proteins of the three rice genes were tested for IGL activity. Os03g58300 had a low Km for indole-3-glycerol phosphate and a high kcat, and hence can efficiently produce indole. Os07g08430 exhibited biochem. properties resembling characterized TSAs. In contrast, Os03g58260 was inactive as a monomer. Anal. of Os03g58300 expression and indole emission provides further support that Os03g58300 is the bona fide rice IGL for biosynthesis of indole, in analogy to maize, this gene is termed OsIgl. Phylogenetic anal. showed that the rice genes are localized in two distinct clades together with the maize genes ZmIgl and ZmBx1 (Os03g58300) and ZmTSA (Os03g58260 and Os07g08430). The genes in the two clades have distinct enzyme activities and gene structures in terms of intron/exon organization. These results suggest that OsIgl evolved after the split of monocot and dicot lineages and before the diversification of the Poaceae.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs1Orur%252FN&md5=5ed01aa82d540d3f76ab492b28506de6
9. 9

   Dunn, M. F. Allosteric Regulation of Substrate Channeling and Catalysis in the Tryptophan Synthase Bienzyme Complex. Arch. Biochem. Biophys. 2012, 519, 154– 166,  DOI: 10.1016/j.abb.2012.01.016

   Google Scholar

   9

   Allosteric regulation of substrate channeling and catalysis in the tryptophan synthase bienzyme complex

   Dunn, Michael F.

   Archives of Biochemistry and Biophysics (2012), 519 (2), 154-166CODEN: ABBIA4; ISSN:0003-9861. (Elsevier B.V.)

   A review. The tryptophan synthase α2β2 bi-enzyme complex catalyzes the last two steps in the synthesis of L-tryptophan (L-Trp). The α-subunit catalyzes cleavage of 3-indole-D-glycerol 3'-phosphate (IGP) to give indole and D-glyceraldehyde 3'-phosphate (G3P). Indole is then transferred (channeled) via an interconnecting 25 Å-long tunnel, from the α-subunit to the β-subunit where it reacts with L-Ser in a pyridoxal 5'-phosphate-dependent reaction to give L-Trp and a water mol. The efficient utilization of IGP and L-Ser by tryptophan synthase to synthesize L-Trp utilizes a system of allosteric interactions that (1) function to switch the α-site on and off at different stages of the β-subunit catalytic cycle, and (2) prevent the escape of the channeled intermediate, indole, from the confines of the α- and β-catalytic sites and the interconnecting tunnel. This review discusses in detail the chem. origins of the allosteric interactions responsible both for switching the α-site on and off, and for triggering the conformational changes between open and closed states which prevent the escape of indole from the bienzyme complex.

   >> More from SciFinder ^®

   https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XjtVOru7o%253D&md5=704869ad5bfe15d0b92a1187d5ffe521
10. 10

    Hyde, C. C.; Ahmed, S. A.; Padlan, E. A.; Miles, E. W.; Davies, D. R. Three-dimensional Structure of the Tryptophan Synthase α₂β₂ Multienzyme Complex from Salmonella typhimurium. J. Biol. Chem. 1988, 263, 17857– 17871,  DOI: 10.1016/s0021-9258(19)77913-7

    Google Scholar

    10

    Three-dimensional structure of the tryptophan synthase α2β2 multienzyme complex from Salmonella typhimurium

    Hyde, C. Craig; Ahmed, S. Ashrafudin; Padlan, Eduardo A.; Miles, Edith W.; Davies, David R.

    Journal of Biological Chemistry (1988), 263 (33), 17857-71CODEN: JBCHA3; ISSN:0021-9258.

    The 3-dimensional structure of the α2β2 complex of tryptophan synthase from S. typhimurium was detd. by x-ray crystallog. at 2.5 Å resoln. The 4 polypeptide chains are arranged nearly linearly in an αββα order forming a complex 150 Å long. The overall polypeptide fold of the smaller α subunit, which cleaves indole glycerol phosphate, is that of an 8-fold α/β barrel. The α subunit active site was located by difference Fourier anal. of the binding of indole propanol phosphate, a competitive inhibitor of the α subunit and a close structural analog of the natural substrate. The larger pyridoxal phosphate-depending β subunit contains 2 domains of nearly equal size, folded into similar helix/sheet/helix structures. The binding site for the coenzyme pyridoxal phosphate lies deep within the interface between the 2 β subunit domains. The active sites of neighboring α and β subunits are sepd. by a distance of ∼25 Å. A tunnel with a diam. match that of the intermediate substrate indole connects these active sites. The tunnel is believed to facilitate the diffusion of indole from its point of prodn. in the α subunit active site to the site of tryptophan synthesis in the β active site and thereby prevent its escape to the solvent during catalysis.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL1cXlvVKgsrY%253D&md5=21d459870837d771f7bab6f672b1e457
11. 11

    Pan, P.; Woehl, E.; Dunn, M. F. Protein Architecture, Dynamics and Allostery in Tryptophan Synthase Channeling. Trends Biochem. Sci. 1997, 22, 22– 27,  DOI: 10.1016/S0968-0004(96)10066-9

    Google Scholar

    11

    Protein architecture, dynamics and allostery in tryptophan synthase channeling

    Pan, Peng; Woehl, Eilika; Dunn, Michael F.

    Trends in Biochemical Sciences (1997), 22 (1), 22-27CODEN: TBSCDB; ISSN:0968-0004. (Elsevier)

    A review, with 25 refs. The α2β2 form of the tryptophan synthase bienzyme complex catalyzes the last two steps in the synthesis of L-tryptophan, consecutive processes that depend on the channeling of the common metabolite, indole, between the sites of the α- and β-subunits through a 25 Å-long tunnel. The channeling of indole and the coupling of the activities of the two sites are controlled by allosteric signals derived from covalent transformations at the β-site that switch the enzyme between an open, low-activity state, to which ligands bind, and a closed high-activity state, which prevents the escape of indole.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2sXhtVOqt7s%253D&md5=ecf854cc95412a6b966e9713630c7516
12. 12

    Fatmi, M. Q.; Ai, R.; Chang, C. A. Synergistic Regulation and Ligand-induced Conformational Changes of Tryptophan Synthase. Biochemistry 2009, 48, 9921– 9931,  DOI: 10.1021/bi901358j

    Google Scholar

    12

    Synergistic Regulation and Ligand-Induced Conformational Changes of Tryptophan Synthase

    Fatmi, M. Qaiser; Ai, Rizi; Chang, Chia-En A.

    Biochemistry (2009), 48 (41), 9921-9931CODEN: BICHAW; ISSN:0006-2960. (American Chemical Society)

    Conformational changes of enzyme complexes are often related to regulating and creating an optimal environment for efficient chem. The synergistic regulation of the tryptophan synthase (TRPS) complex, studied for decades as a model of allosteric regulation and substrate channeling within protein complexes, was investigated. TRPS is a bifunctional tetrameric αββα enzyme complex that exhibits cooperative motions of the α- and β-subunits by tightly controlled allosteric interactions. The atomically detailed dynamics and conformational changes of TRPS were delineated in the absence and presence of substrates using mol. dynamics simulations. The computed energy and entropy assocd. with the protein motions also offer mechanistic insights into the conformational fluctuations and the ligand binding mechanism. The flexible α-L6 loop samples both open and partially closed conformations in the ligand-free state but shifts to fully closed conformations when its substrates are present. The fully closed conformations are induced by favorable protein-ligand interactions but are partly compensated by configurational entropy loss. Considerable local rearrangements exist during ligand binding processes when the system is searching for energy min. The motion of the region that closes the β-subunit during catalysis, the COMM domain, couples with the motion of the α-subunit, although the fluctuations are smaller than in the flexible loop regions. Because of multiple conformations of ligand-free TRPS in the open and partially closed states, the α-L6 loop fluctuations have preferential directionality, which may facilitate the fully closed conformations induced by α- and β-substrates binding to both subunits. Such cooperative and directional motion may be a general feature that contributes to catalysis in many enzyme complexes.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtFynsLzF&md5=bfad3e498bc3cce41258f8d1d0d750f2
13. 13

    Schupfner, M.; Busch, F.; Wysocki, V. H.; Sterner, R. Generation of a Stand-Alone Tryptophan Synthase α-Subunit by Mimicking an Evolutionary Blueprint. ChemBioChem 2019, 20, 2747– 2751,  DOI: 10.1002/cbic.201900323

    Google Scholar

    13

    Generation of a Stand-Alone Tryptophan Synthase α-Subunit by Mimicking an Evolutionary Blueprint

    Schupfner, Michael; Busch, Florian; Wysocki, Vicki H.; Sterner, Reinhard

    ChemBioChem (2019), 20 (21), 2747-2751CODEN: CBCHFX; ISSN:1439-4227. (Wiley-VCH Verlag GmbH & Co. KGaA)

    The αββα tryptophan synthase (TS), which is part of primary metab., is a paradigm for allosteric communication in multienzyme complexes. In particular, the intrinsically low catalytic activity of the α-subunit TrpA is stimulated several hundredfold through the interaction with the β-subunit TrpB1. The BX1 protein from Zea mays (zmBX1), which is part of secondary metab., catalyzes the same reaction as that of its homolog TrpA, but with high activity in the absence of an interaction partner. The intrinsic activity of TrpA can be significantly increased through the exchange of several active-site loop residues, which mimic the corresponding loop in zmBX1. The subsequent identification of activating amino acids in the generated "stand-alone" TrpA contributes to an understanding of allostery in TS. Moreover, findings suggest an evolutionary trajectory that describes the transition from a primary metabolic enzyme regulated by an interaction partner to a self-reliant, stand-alone, secondary metabolic enzyme.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhs1CmsLbM&md5=7e35d52bd922682d09731c435fad1f64
14. 14

    Wendisch, V. F. Metabolic Engineering Advances and Prospects for Amino Acid Production. Metab. Eng. 2020, 58, 17– 34,  DOI: 10.1016/j.ymben.2019.03.008

    Google Scholar

    14

    Metabolic engineering advances and prospects for amino acid production

    Wendisch, Volker F.

    Metabolic Engineering (2020), 58 (), 17-34CODEN: MEENFM; ISSN:1096-7176. (Elsevier B.V.)

    A review. Amino acid fermn. is one of the major pillars of industrial biotechnol. The multi-billion USD amino acid market is rising steadily and is diversifying. Metabolic engineering is no longer focused solely on strain development for the bulk amino acids L-glutamate and L-lysine that are produced at the million-ton scale, but targets specialty amino acids. These demands are met by the development and application of new metabolic engineering tools including CRISPR and biosensor technologies as well as prodn. processes by enabling a flexible feedstock concept, co-prodn. and co-cultivation schemes. Metabolic engineering advances are exemplified for specialty proteinogenic amino acids, cyclic amino acids, omega-amino acids, and amino acids functionalized by hydroxylation, halogenation and N-methylation.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXms1Ontro%253D&md5=61c1a696d9e87a132acd117b46d60a15
15. 15

    Niu, H.; Li, R.; Liang, Q.; Qi, Q.; Li, Q.; Gu, P. Metabolic Engineering for Improving L-Tryptophan Production in Escherichia coli. J. Ind. Microbiol. Biotechnol. 2019, 46, 55– 65,  DOI: 10.1007/s10295-018-2106-5

    Google Scholar

    15

    Metabolic engineering for improving L-tryptophan production in Escherichia coli

    Niu, Hao; Li, Ruirui; Liang, Quanfeng; Qi, Qingsheng; Li, Qiang; Gu, Pengfei

    Journal of Industrial Microbiology & Biotechnology (2019), 46 (1), 55-65CODEN: JIMBFL; ISSN:1367-5435. (Springer)

    L-Tryptophan is an important arom. amino acid that is used widely in the food, chem., and pharmaceutical industries. Compared with the traditional synthetic methods, prodn. of L-tryptophan by microbes is environmentally friendly and has low prodn. costs, and feed stocks are renewable. With the development of metabolic engineering, highly efficient prodn. of L-tryptophan in Escherichia coli has been achieved by eliminating neg. regulation factors, improving the intracellular level of precursors, engineering of transport systems and overexpression of rate-limiting enzymes. However, challenges remain for L-tryptophan biosynthesis to be cost-competitive. In this review, successful and applicable strategies derived from metabolic engineering for increasing L-tryptophan accumulation in E. coli are summarized. In addn., perspectives for further efficient prodn. of L-tryptophan are discussed.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXit1SgtbvL&md5=a6a72c9f409c8f5006a69fb64f2c5312
16. 16

    Ikeda, M.; Katsumata, R. Hyperproduction of Tryptophan by Corynebacterium glutamicum with the Modified Pentose Phosphate Pathway. Appl. Environ. Microbiol. 1999, 65, 2497– 2502,  DOI: 10.1128/AEM.65.6.2497-2502.1999

    Google Scholar

    16

    Hyperproduction of tryptophan by Corynebacterium glutamicum with the modified pentose phosphate pathway

    Ikeda, Masato; Katsumata, Ryoichi

    Applied and Environmental Microbiology (1999), 65 (6), 2497-2502CODEN: AEMIDF; ISSN:0099-2240. (American Society for Microbiology)

    A classically derived tryptophan-producing Corynebacterium glutamicum strain was recently significantly improved both by plasmid-mediated amplification of the genes for the rate-limiting enzymes in the terminal pathways and by construction of a plasmid stabilization system so that it produced more tryptophan. This engineered strain, KY9218 carrying pKW9901, produced 50 g of tryptophan per L from sucrose after 80 h in fed-batch cultivation without antibiotic pressure. Anal. of carbon balances showed that at the late stage of the fermn., tryptophan yield decreased with a concomitant increase in CO2 yield, suggesting a transition in the distribution of carbon flow from arom. biosynthesis toward the tricarboxylic acid cycle via glycolysis. To circumvent this transition by increasing the supply of erythrose 4-phosphate, a direct precursor of arom. biosynthesis, the transketolase gene of C. glutamicum was coamplified in the engineered strain by using low- and high-copy-no. plasmids which were compatible with the resident plasmid pKW9901. The presence of the gene in low copy nos. contributed to improvement of tryptophan yield, esp. at the late stage, and led to accumulation of more tryptophan (57 g/L) than did its absence, while high-copy-no. amplification of the gene resulted in a tryptophan prodn. level even lower than that resulting from the absence of the gene due to reduced growth and sugar consumption. In order to assemble all the cloned genes onto a low-copy-no. plasmid, the high-copy-no. origin of pKW9901 was replaced with the low-copy-no. one, generating low-copy-no. plasmid pSW9911, and the transketolase gene was inserted to yield pIK9960. The pSW9911-carrying producer showed almost the same fermn. profiles as the pKW9901 carrier in fed-batch cultivation without antibiotic pressure. Under the same culture conditions, however, the pIK9960 carrier achieved a final tryptophan titer of 58 g/L, which represented a 15% enhancement over the titers achieved by the pKW9901 and pSW9911 carriers.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXjs12gsbo%253D&md5=7ad4d09a39bc1022479ff307bbdd2b81
17. 17

    Mindt, M.; Kashkooli, A. B.; Suarez-Diez, M.; Ferrer, L.; Jilg, T.; Bosch, D.; Martins Dos Santos, V.; Wendisch, V. F.; Cankar, K. Production of Indole by Corynebacterium glutamicum Microbial Cell Factories for Flavor and Fragrance Applications. Microb. Cell Fact. 2022, 21, 45  DOI: 10.1186/s12934-022-01771-y

    Google Scholar

    17

    Production of indole by Corynebacterium glutamicum microbial cell factories for flavor and fragrance applications

    Mindt, Melanie; Beyraghdar Kashkooli, Arman; Suarez-Diez, Maria; Ferrer, Lenny; Jilg, Tatjana; Bosch, Dirk; Martins dos Santos, Vitor; Wendisch, Volker F.; Cankar, Katarina

    Microbial Cell Factories (2022), 21 (1), 45CODEN: MCFICT; ISSN:1475-2859. (BioMed Central Ltd.)

    The nitrogen contg. arom. compd. indole is known for its floral odor typical of jasmine blossoms. Due to its characteristic scent, it is frequently used in dairy products, tea drinks and fine fragrances. The demand for natural indole by the flavor and fragrance industry is high, yet, its abundance in essential oils isolated from plants such as jasmine and narcissus is low. Thus, there is a strong demand for a sustainable method to produce food-grade indole. Here, we established the biotechnol. prodn. of indole upon L-tryptophan supplementation in the bacterial host Corynebacterium glutamicum. Heterologous expression of the tryptophanase gene from E. coli enabled the conversion of supplemented L-tryptophan to indole. Engineering of the substrate import by co-expression of the native arom. amino acid permease gene aroP increased whole-cell biotransformation of L-tryptophan to indole by two-fold. Indole prodn. to 0.2 g L-1 was achieved upon feeding of 1 g L-1L-tryptophan in a bioreactor cultivation, while neither accumulation of side-products nor loss of indole were obsd. To establish an efficient and robust prodn. process, new tryptophanases were recruited by mining of bacterial sequence databases. This search retrieved more than 400 candidates and, upon screening of tryptophanase activity, nine new enzymes were identified as most promising. The highest prodn. of indole in vivo in C. glutamicum was achieved based on the tryptophanase from Providencia rettgeri. Evaluation of several biol. aspects identified the product toxicity as major bottleneck of this conversion. In situ product recovery was applied to sequester indole in a food-grade org. phase during the fermn. to avoid inhibition due to product accumulation. This process enabled complete conversion of L-tryptophan and an indole product titer of 5.7 g L-1 was reached. Indole partitioned to the org. phase which contained 28 g L-1 indole while no other products were obsd. indicating high indole purity. The bioconversion prodn. process established in this study provides an attractive route for sustainable indole prodn. from tryptophan in C. glutamicum. Industrially relevant indole titers were achieved within 24 h and indole was concd. in the org. layer as a pure product after the fermn.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhtVWrsrbJ&md5=ee9211a8de4a359687fc1f881060531b
18. 18

    Hanahan, D. Studies on Transformation of Escherichia coli with plasmids. J. Mol. Biol. 1983, 166, 557– 580,  DOI: 10.1016/s0022-2836(83)80284-8

    Google Scholar

    18

    Studies on transformation of Escherichia coli with plasmids

    Hanahan, Douglas

    Journal of Molecular Biology (1983), 166 (4), 557-80CODEN: JMOBAK; ISSN:0022-2836.

    Factors that affect the probability of genetic transformation of E. coli by plasmids were evaluated. A set of conditions is described under which ∼1 in every 400 plasmid mols. produces a transformed cell. These conditions include cell growth in medium contg. elevated levels of Mg2+, and incubation of the cells at 0° in a soln. of Mn2+, Ca2+, Rb+, or K+, DMSO, dithiothreitol, and hexamine Co(III). Transformation efficiency declines linearly with increasing plasmid size. Relaxed and supercoiled plasmids transform with similar probabilities. Nontransforming DNAs compete consistent with mass. No significant variation is obsd. between competing DNAs of different source, complexity, length, or form. Competition with both transforming and nontransforming plasmid indicates that each cell is capable of taking up many DNA mols., and that the establishment of a transformation event is neither helped nor hindered significantly by the presence of multiple plasmids.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3sXkvVCqtL4%253D&md5=070c42463815989750888248982f8731
19. 19

    Simon, R.; Priefer, U.; Pühler, A. A Broad Host Range Mobilization Sytem for In vivo Genetic engineering: Transposon Mutagenesis in Gram Negative Bacteria. Nat. Biotechnol. 1983, 1, 784– 791,  DOI: 10.1038/nbt1183-784

    Google Scholar

    19

    A broad host range mobilization system for in vivo genetic engineering: transportation mutagenesis in gram negative bacteria

    Simon, R.; Priefer, U.; Puehler, A.

    Bio/Technology (1983), 1 (9), 784-91CODEN: BTCHDA; ISSN:0733-222X.

    A new vector strategy was developed for the insertion of foreign genes into the genomes of gram-neg. bacteria not closely related to Escherichia coli. The system consists of 2 components: special E. coli donor strains and derivs. of E. coli vector plasmids. The donor strains (called mobilizing strains) carry the transfer genes of the broad host range IncP-type plasmid RP4 integrated in their chromosomes. They can utilize any gram-neg. bacterium as a recipient for conjugative DNA transfer. The vector plasmids contain the P-type specific recognition site for mobilization (Mob site) and can be mobilized with high frequency from the donor strains. The mobilizable vectors are derived from the commonly used E. coli vectors pACYC184, pACYC177, and pBR325 and are unable to replicate in strains outside the enteric bacterial group. Therefore, they are widely applicable as transposon carrier replicons for random transposon insertion mutagenesis in any strain into which they can be mobilized but not stably maintained. The vectors are esp. useful for site-directed transposon mutagenesis and for site-specific gene transfer in a wide variety of gram-neg. organisms.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL2cXotVCqsg%253D%253D&md5=396935a30188f7e4f741cdb41fb71aee
20. 20

    Baumgart, M.; Unthan, S.; Kloß, R.; Radek, A.; Polen, T.; Tenhaef, N.; Müller, M. F.; Küberl, A.; Siebert, D.; Brühl, N.; Marin, K.; Hans, S.; Krämer, R.; Bott, M.; Kalinowski, J.; Wiechert, W.; Seibold, G.; Frunzke, J.; Rückert, C.; Wendisch, V. F.; Noack, S. Corynebacterium glutamicum Chassis C1*: Building and Testing a Novel Platform Host for Synthetic Biology and Industrial Biotechnology. ACS Synth. Biol. 2018, 7, 132– 144,  DOI: 10.1021/acssynbio.7b00261

    Google Scholar

    20

    Corynebacterium glutamicum Chassis C1*: Building and Testing a Novel Platform Host for Synthetic Biology and Industrial Biotechnology

    Baumgart, Meike; Unthan, Simon; Kloss, Ramona; Radek, Andreas; Polen, Tino; Tenhaef, Niklas; Mueller, Moritz Fabian; Kueberl, Andreas; Siebert, Daniel; Bruehl, Natalie; Marin, Kay; Hans, Stephan; Kraemer, Reinhard; Bott, Michael; Kalinowski, Joern; Wiechert, Wolfgang; Seibold, Gerd; Frunzke, Julia; Rueckert, Christian; Wendisch, Volker F.; Noack, Stephan

    ACS Synthetic Biology (2018), 7 (1), 132-144CODEN: ASBCD6; ISSN:2161-5063. (American Chemical Society)

    Targeted top-down strategies for genome redn. are considered to have a high potential for providing robust basic strains for synthetic biol. and industrial biotechnol. Recently, we created a library of 26 genome-reduced strains of Corynebacterium glutamicum carrying broad deletions in single gene clusters and showing wild-type-like biol. fitness. Here, we proceeded with combinatorial deletions of these irrelevant gene clusters in two parallel orders, and the resulting library of 28 strains was characterized under various environmental conditions. The final chassis strain C1* carries a genome redn. of 13.4% (412 deleted genes) and shows wild-type-like growth behavior in defined medium with D-glucose as carbon and energy source. Moreover, C1* proves to be robust against several stresses (including oxygen limitation) and shows long-term growth stability under defined and complex medium conditions. In addn. to providing a novel prokaryotic chassis strain, our results comprise a large strain library and a revised genome annotation list, which will be valuable sources for future systemic studies of C. glutamicum.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtlSkur%252FP&md5=91e826ffbf02f8a5a7c60d7a2943efd3
21. 21

    Walter, T.; Al Medani, N.; Burgardt, A.; Cankar, K.; Ferrer, L.; Kerbs, A.; Lee, J.-H.; Mindt, M.; Risse, J. M.; Wendisch, V. F. Fermentative N-Methylanthranilate Production by Engineered Corynebacterium glutamicum. Microorganisms 2020, 8, 866  DOI: 10.3390/microorganisms8060866

    Google Scholar

    21

    Fermentative N-methylanthranilate production by engineered Corynebacterium glutamicum

    Walter, Tatjana; Al Medani, Nour; Burgardt, Arthur; Cankar, Katarina; Ferrer, Lenny; Kerbs, Anastasia; Lee, Jin-Ho; Mindt, Melanie; Risse, Joe Max; Wendisch, Volker F.

    Microorganisms (2020), 8 (6), 866CODEN: MICRKN; ISSN:2076-2607. (MDPI AG)

    The N-functionalized amino acid N-methylanthranilate is an important precursor for bioactive compds. such as anticancer acridone alkaloids, the antinociceptive alkaloid O-iso-Pr N-methylanthranilate, the flavor compd. O-methyl-N-methylanthranilate, and as a building block for peptide-based drugs. Current chem. and biocatalytic synthetic routes to N-alkylated amino acids are often unprofitable and restricted to low yields or high costs through cofactor regeneration systems. Amino acid fermn. processes using the Gram-pos. bacterium Corynebacterium glutamicum are operated industrially at the million tons per annum scale. Fermentative processes using C. glutamicum for N-alkylated amino acids based on an imine reductase have been developed, while N-alkylation of the arom. amino acid anthranilate with S-adenosyl methionine as methyl-donor has not been described for this bacterium. After metabolic engineering for enhanced supply of anthranilate by channeling carbon flux into the shikimate pathway, preventing byproduct formation and enhancing sugar uptake, heterologous expression of the gene anmt encoding anthranilate N-methyltransferase from Ruta graveolens resulted in prodn. of N-methylanthranilate (NMA), which accumulated in the culture medium. Increased SAM regeneration by coexpression of the homologous adenosylhomocysteinase gene sahH improved N-methylanthranilate prodn. In a test bioreactor culture, the metabolically engineered C. glutamicum C1* strain produced NMA to a final titer of 0.5 g·L-1 with a volumetric productivity of 0.01 g·L-1 ·h-1 and a yield of 4.8 mg·g-1 glucose.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXitlyjtrjJ&md5=642cd304c8522da4f46ca886d1c450bd
22. 22

    Schäfer, A.; Tauch, A.; Jäger, W.; Kalinowski, J.; Thierbachb, G.; Pühler, A. Small Mobilizable Multi-Purpose Cloning Vectors Derived from the Escherichia coli Plasmids pK18 and pK19: Selection of Defined Deletions in the Chromosome of Corynebacterium glutamicum. Gene 1994, 145, 69– 73,  DOI: 10.1016/0378-1119(94)90324-7

    Google Scholar

    22

    Small mobilizable multi-purpose cloning vectors derived from the Escherichia coli plasmids pK18 and pK19: selection of defined deletions in the chromosome of Corynebacterium glutamicum

    Schafer A; Tauch A; Jager W; Kalinowski J; Thierbach G; Puhler A

    Gene (1994), 145 (1), 69-73 ISSN:0378-1119.

    Here we describe small mobilizable vectors based on the Escherichia coli plasmids pK18 and pK19. We combined the useful properties of the pK plasmids (e.g., multiple cloning site, lacZ alpha fragment, sequencing with M13 primers) with the broad-host-range transfer machinery of plasmid RP4 and a modified sacB gene from Bacillus subtilis. The new pK derivatives can be transferred by RP4-mediated conjugation into a wide range of Gram- and Gram+ bacteria, and should facilitate gene disruption and allelic exchange by homologous recombination. As an application example, the generation of a defined deletion of the hom-thrB genes in the chromosome of the Gram+ bacterium Corynebacterium glutamicum is presented.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK2czitVOruw%253D%253D&md5=508475c88415e27552b136dfcec017d5
23. 23

    Li, P.-P.; Liu, Y.-J.; Liu, S.-J. Genetic and Biochemical Identification of the Chorismate Mutase from Corynebacterium glutamicum. Microbiology 2009, 155, 3382– 3391,  DOI: 10.1099/mic.0.029819-0

    Google Scholar

    23

    Genetic and biochemical identification of the chorismate mutase from Corynebacterium glutamicum

    Li, Pan-Pan; Liu, Ya-Jun; Liu, Shuang-Jiang

    Microbiology (Reading, United Kingdom) (2009), 155 (10), 3382-3391CODEN: MROBEO; ISSN:1350-0872. (Society for General Microbiology)

    Chorismate mutase (CM) catalyzes the rearrangement of chorismate to prephenate and is also the first and the key enzyme that diverges the shikimate pathway to either tryptophan (Trp) or phenylalanine (Phe) and tyrosine (Tyr). Corynebacterium glutamicum is one of the most important amino acid producers for the fermn. industry and has been widely investigated. However, the gene(s) encoding CM has not been exptl. identified in C. glutamicum. In this study, the ncgl0819 gene, which was annotated as 'conserved hypothetical protein' in the C. glutamicum genome, was genetically characterized to be essential for growth in minimal medium, and a mutant deleted of ncgl0819 was a Phe and Tyr auxotroph. Genetic cloning and expression of ncgl0819 in Escherichia coli resulted in the formation of a new protein (NCgl0819) having CM activity. It was concluded that ncgl0819 encoded the CM of C. glutamicum (CM0819). CM0819 was demonstrated to be a homodimer and is a new member of the monofunctional CMs of the AroQ structural class. The CM0819 activity was not affected by Phe, Tyr or Trp. Two 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthases (DS0950 and DS2098, formerly NCgl0950 and NCgl2098) had been previously identified from C. glutamicum. CM0819 significantly stimulated DAHP synthase (DS2098) activity. Phys. interaction between CM0819 and DS2098 was obsd. When CM0819 was present, DS2098 activity was subject to allosteric inhibition by chorismate and prephenate. Conserved hypothetical proteins homologous to CM0819 were identified in all known Corynebacterium genomes, suggesting a universal occurrence of CM0819-like CMs in the genus Corynebacterium.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtlenurrE&md5=9909a070aecaf75d82dbd99bf7e7418d
24. 24

    Pérez-García, F.; Brito, L. F.; Wendisch, V. F. Function of L-Pipecolic Acid as Compatible Solute in Corynebacterium glutamicum as Basis for its Production Under Hyperosmolar Conditions. Front. Microbiol. 2019, 10, 340  DOI: 10.3389/fmicb.2019.00340

    Google Scholar

    24

    Function of L-Pipecolic Acid as Compatible Solute in Corynebacterium glutamicum as Basis for Its Production Under Hyperosmolar Conditions

    Perez-Garcia Fernando; Brito Luciana F; Wendisch Volker F

    Frontiers in microbiology (2019), 10 (), 340 ISSN:1664-302X.

    Pipecolic acid or L-PA is a cyclic amino acid derived from L-lysine which has gained interest in the recent years within the pharmaceutical and chemical industries. L-PA can be produced efficiently using recombinant Corynebacterium glutamicum strains by expanding the natural L-lysine biosynthetic pathway. L-PA is a six-membered ring homolog of the five-membered ring amino acid L-proline, which serves as compatible solute in C. glutamicum. Here, we show that de novo synthesized or externally added L-PA partially is beneficial for growth under hyper-osmotic stress conditions. C. glutamicum cells accumulated L-PA under elevated osmotic pressure and released it after an osmotic down shock. In the absence of the mechanosensitive channel YggB intracellular L-PA concentrations increased and its release after osmotic down shock was slower. The proline permease ProP was identified as a candidate L-PA uptake system since RNAseq analysis revealed increased proP RNA levels upon L-PA production. Under hyper-osmotic conditions, a ΔproP strain showed similar growth behavior than the parent strain when L-proline was added externally. By contrast, the growth impairment of the ΔproP strain under hyper-osmotic conditions could not be alleviated by addition of L-PA unless proP was expressed from a plasmid. This is commensurate with the view that L-proline can be imported into the C. glutamicum cell by ProP and other transporters such as EctP and PutP, while ProP appears of major importance for L-PA uptake under hyper-osmotic stress conditions.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3cbivV2iug%253D%253D&md5=46567570f6a52163524b45e9b494c181
25. 25

    Veldmann, K. H.; Minges, H.; Sewald, N.; Lee, J.-H.; Wendisch, V. F. Metabolic Engineering of Corynebacterium glutamicum for the Fermentative Production of Halogenated Tryptophan. J. Biotechnol. 2019, 291, 7– 16,  DOI: 10.1016/j.jbiotec.2018.12.008

    Google Scholar

    25

    Metabolic engineering of Corynebacterium glutamicum for the fermentative production of halogenated tryptophan

    Veldmann, Kareen H.; Minges, Hannah; Sewald, Norbert; Lee, Jin-Ho; Wendisch, Volker F.

    Journal of Biotechnology (2019), 291 (), 7-16CODEN: JBITD4; ISSN:0168-1656. (Elsevier B.V.)

    Halogenated compds., like 7-chloro-L-tryptophan, are important intermediates or components of bioactive substances relevant for the pharmaceutical, chem. and agrochem. industries. About 20% of all pharmaceutical small mol. drugs and around 30% of all active compds. in agrochem. are halogenated. Chem. halogenation procedures usually are characterized by the use of hazardous or even highly toxic chems. Recently, a biocatalytic process for L-tryptophan halogenation at the gram-scale using FAD-dependent halogenase and NADH-dependent flavin reductase enzymes has been described. Many proteinogenic amino acids are produced by fermn. using Corynebacterium glutamicum. The fermentative prodn. of L-glutamate and L-lysine, for example, is operated at the million-ton scale. However, fermentative prodn. of halogenated amino acids has not yet been described. In this study, fermentative prodn. of the halogenated amino acid 7-chloro-L-tryptophan from sugars, ammonium and chloride salts was achieved. This required metabolic engineering of an L-tryptophan producing C. glutamicum strain for expression of the genes coding for FAD-dependent halogenase RebH and NADH-dependent flavin reductase RebF from Lechevalieria aerocolonigenes. Chlorination of L-tryptophan to 7-chloro-L-tryptophan by recombinant C. glutamicum was improved by optimizing the RBS of rebH. Metabolic engineering enabled prodn. of 7-chloro-L-tryptophan and L-tryptophan from the alternative carbon sources arabinose, glucosamine and xylose.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXis1Srt73M&md5=d093f4a271570f80a5226720854eda0b
26. 26

    Stansen, C.; Uy, D.; Delaunay, S.; Eggeling, L.; Goergen, J.-L.; Wendisch, V. F. Characterization of a Corynebacterium glutamicum Lactate Utilization Operon Induced During Temperature-Triggered Glutamate Production. Appl. Environ. Microbiol. 2005, 71, 5920– 5928,  DOI: 10.1128/AEM.71.10.5920-5928.2005

    Google Scholar

    26

    Characterization of a Corynebacterium glutamicum lactate utilization operon induced during temperature-triggered glutamate production

    Stansen, Corinna; Uy, Davin; Delaunay, Stephane; Eggeling, Lothar; Goergen, Jean-Louis; Wendisch, Volker F.

    Applied and Environmental Microbiology (2005), 71 (10), 5920-5928CODEN: AEMIDF; ISSN:0099-2240. (American Society for Microbiology)

    Gene expression changes of glutamate-producing Corynebacterium glutamicum were identified in transcriptome comparisons by DNA microarray anal. During glutamate prodn. induced by a temp. shift, C. glutamicum strain 2262 showed significantly higher mRNA levels of the NCgl2816 and NCgl2817 genes than its non-glutamate-producing deriv. 2262NP. Reverse transcription-PCR anal. showed that the two genes together constitute an operon. NCgl2816 putatively codes for a lactate permease, while NCgl2817 was demonstrated to encode quinone-dependent L-lactate dehydrogenase, which was named LldD. C. glutamicum LldD displayed Michaelis-Menten kinetics for the substrate L-lactate with a Km of about 0.51 mM. The specific activity of LldD was about 10-fold higher during growth on L-lactate or on an L-lactate-glucose mixt. than during growth on glucose, D-lactate, or pyruvate, while the specific activity of quinone-dependent D-lactate dehydrogenase differed little with the carbon source. RNA levels of NCgl2816 and lldD were about 18-fold higher during growth on L-lactate than on pyruvate. Disruption of the NCgl2816-llldD operon resulted in loss of the ability to utilize L-lactate as the sole carbon source. Expression of lllD restored L-lactate utilization, indicating that the function of the permease gene NCgl2816 is dispensable, while LldD is essential, for growth of C. glutamicum on L-lactate.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtFajtbvN&md5=db31ae6e45d0c7a5ec7e000cb569b3dd
27. 27

    Kirchner, O.; Tauch, A. Tools for Genetic Engineering in the Amino Acid-Producing Bacterium Corynebacterium glutamicum. J. Biotechnol. 2003, 104, 287– 299,  DOI: 10.1016/S0168-1656(03)00148-2

    Google Scholar

    27

    Tools for genetic engineering in the amino acid-producing bacterium Corynebacterium glutamicum

    Kirchner, Oliver; Tauch, Andreas

    Journal of Biotechnology (2003), 104 (1-3), 287-299CODEN: JBITD4; ISSN:0168-1656. (Elsevier Science B.V.)

    During the last decades, the gram-pos. soil bacterium Corynebacterium glutamicum has been shown to be a very versatile microorganism for the large-scale fermentative prodn. of l-amino acids. Up to now, a vast amt. of techniques and tools for genetic engineering and amplification of relevant structural genes have been developed. The objectives of this study are to summarize the published literature on tools for genetic engineering in C. glutamicum and to focus on new sophisticated and highly efficient methods in the fields of DNA transfer techniques, cloning vectors, integrative genetic tools, and antibiotic-free self-cloning. This repertoire of C. glutamicum methodol. provides an exptl. basis for efficient genetic analyses of the recently completed genome sequence.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXmslensLY%253D&md5=9d82187e26ebfe9240eb4b73638b1231
28. 28

    Eggeling, L.; Bott, M. Handbook of Corynebacterium glutamicum; CRC Press: Boca Raton, FL, 2005.

    Google Scholar

    There is no corresponding record for this reference.
29. 29

    Green, M. R.; Sambrook, J. Molecular Cloning: A Laboratory Manual, 4th ed.; Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY, 2012.

    Google Scholar

    There is no corresponding record for this reference.
30. 30

    Engler, C.; Kandzia, R.; Marillonnet, S. A One Pot, One Step, Precision Cloning Method with High Throughput Capability. PLoS One 2008, 3, e3647  DOI: 10.1371/journal.pone.0003647

    Google Scholar

    30

    A one pot, one step, precision cloning method with high throughput capability

    Engler Carola; Kandzia Romy; Marillonnet Sylvestre

    PloS one (2008), 3 (11), e3647 ISSN:.

    Current cloning technologies based on site-specific recombination are efficient, simple to use, and flexible, but have the drawback of leaving recombination site sequences in the final construct, adding an extra 8 to 13 amino acids to the expressed protein. We have devised a simple and rapid subcloning strategy to transfer any DNA fragment of interest from an entry clone into an expression vector, without this shortcoming. The strategy is based on the use of type IIs restriction enzymes, which cut outside of their recognition sequence. With proper design of the cleavage sites, two fragments cut by type IIs restriction enzymes can be ligated into a product lacking the original restriction site. Based on this property, a cloning strategy called 'Golden Gate' cloning was devised that allows to obtain in one tube and one step close to one hundred percent correct recombinant plasmids after just a 5 minute restriction-ligation. This method is therefore as efficient as currently used recombination-based cloning technologies but yields recombinant plasmids that do not contain unwanted sequences in the final construct, thus providing precision for this fundamental process of genetic manipulation.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1cjhvV2ltA%253D%253D&md5=8910183a67aa28a0cc69522dcf7050b0
31. 31

    Gibson, D. G.; Young, L.; Chuang, R.-Y.; Craig Venter, J.; Hutchison, C. A., III; Smith, H. O. Enzymatic Assembly of DNA Molecules up to Several Hundred Kilobases. Nat. Methods 2009, 6, 343– 345,  DOI: 10.1038/nmeth.1318

    Google Scholar

    31

    Enzymatic assembly of DNA molecules up to several hundred kilobases

    Gibson, Daniel G.; Young, Lei; Chuang, Ray-Yuan; Venter, J. Craig; Hutchison, Clyde A.; Smith, Hamilton O.

    Nature Methods (2009), 6 (5), 343-345CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)

    The authors describe an isothermal, single-reaction method for assembling multiple overlapping DNA mols. by the concerted action of a 5' exonuclease, a DNA polymerase and a DNA ligase. First they recessed DNA fragments, yielding single-stranded DNA overhangs that specifically annealed, and then covalently joined them. This assembly method can be used to seamlessly construct synthetic and natural genes, genetic pathways and entire genomes, and could be a useful mol. engineering tool.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXksVemsbw%253D&md5=46284924c7d73c47cfb490983338e480
32. 32

    Luo, Z. W.; Cho, J. S.; Lee, S. Y. Microbial Production of Methyl Anthranilate, a Grape Flavor Compound. Proc. Natl. Acad. Sci. U.S.A. 2019, 116, 10749– 10756,  DOI: 10.1073/pnas.1903875116

    Google Scholar

    32

    Microbial production of methyl anthranilate, a grape flavor compound

    Luo, Zi Wei; Cho, Jae Sung; Lee, Sang Yup

    Proceedings of the National Academy of Sciences of the United States of America (2019), 116 (22), 10749-10756CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)

    Me anthranilate (MANT) is a widely used compd. to give grape scent and flavor, but is currently produced by petroleum-based processes. Here, we report the direct fermentative prodn. of MANT from glucose by metabolically engineered Escherichia coli and Corynebacterium glutamicum strains harboring a synthetic plant-derived metabolic pathway. Optimizing the key enzyme anthranilic acid (ANT) methyltransferase 1 (AAMT1) expression, increasing the direct precursor ANT supply, and enhancing the intracellular availability and salvage of the cofactor S-adenosyl-l-methionine required by AAMT1, results in improved MANT prodn. in both engineered microorganisms. Furthermore, in situ two-phase extractive fermn. using tributyrin as an extractant is developed to overcome MANT toxicity. Fed-batch cultures of the final engineered E. coli and C. glutamicum strains in two-phase cultivation mode led to the prodn. of 4.47 and 5.74 g/L MANT, resp., in minimal media contg. glucose. The metabolic engineering strategies developed here will be useful for the prodn. of volatile arom. esters including MANT.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtVChsrzJ&md5=84a9a59ef0fae4ec21d1f967d00b32be
33. 33

    Zhang, Y.; Cai, J.; Shang, X.; Wang, B.; Liu, S.; Chai, X.; Tan, T.; Zhang, Y.; Wen, T. A New Genome-scale Metabolic Model of Corynebacterium glutamicum and its Application. Biotechnol. Biofuels 2017, 10, 169  DOI: 10.1186/s13068-017-0856-3

    Google Scholar

    33

    A new genome-scale metabolic model of Corynebacterium glutamicum and its application

    Zhang, Yu; Cai, Jingyi; Shang, Xiuling; Wang, Bo; Liu, Shuwen; Chai, Xin; Tan, Tianwei; Zhang, Yun; Wen, Tingyi

    Biotechnology for Biofuels (2017), 10 (), 169/1-169/16CODEN: BBIIFL; ISSN:1754-6834. (BioMed Central Ltd.)

    Corynebacterium glutamicum is an important platform organism for industrial biotechnol. to produce amino acids, org. acids, bioplastic monomers, and biofuels. The metabolic flexibility, broad substrate spectrum, and fermentative robustness of C. glutamicum make this organism an ideal cell factory to manuf. desired products. With increases in gene function, transport system, and metabolic profile information under certain conditions, developing a comprehensive genome-scale metabolic model (GEM) of C. glutamicum ATCC13032 is desired to improve prediction accuracy, elucidate cellular metab., and guide metabolic engineering. Here, we constructed a new GEM for ATCC13032, iCW773, consisting of 773 genes, 950 metabolites, and 1207 reactions. Compared to the previous model, iCW773 supplemented 496 geneaeuro"protein-reaction assocns., refined five lumped reactions, balanced the mass and charge, and constrained the directionality of reactions. The simulated growth rates of C. glutamicum cultivated on seven different carbon sources using iCW773 were consistent with exptl. values. Pearson's correlation coeff. between the iCW773-simulated and exptl. fluxes was 0.99, suggesting that iCW773 provided an accurate intracellular flux distribution of the wild-type strain growing on glucose. Furthermore, genetic interventions for overproducing L-lysine, 1,2-propanediol and isobutanol simulated using OptForceMUST were in accordance with reported exptl. results, indicating the practicability of iCW773 for the design of metabolic networks to overproduce desired products. In vivo genetic modifications of iCW773- predicted targets resulted in the de novo generation of an L-proline-overproducing strain. In fed-batch culture, the engineered C. glutamicum strain produced 66.43 g/L L-proline in 60 h with a yield of 0.26 g/g (L-proline/glucose) and a productivity of 1.11 g/L/h. To our knowledge, this is the highest titer and productivity reported for L-proline prodn. using glucose as the carbon resource in a minimal medium. Our developed iCW773 serves as a high-quality platform for model-guided strain design to produce industrial bioproducts of interest. This new GEM will be a successful multidisciplinary tool and will make valuable contributions to metabolic engineering in academia and industry.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVOrs7fN&md5=b00038b5f50f79580228789c8f8915d0
34. 34

    Ebrahim, A.; Lerman, J. A.; Palsson, B. O.; Hyduke, D. R. COBRApy: COnstraints-Based Reconstruction and Analysis for Python. BMC Syst. Biol. 2013, 7, 74  DOI: 10.1186/1752-0509-7-74

    Google Scholar

    34

    COBRApy: COnstraints-Based Reconstruction and Analysis for Python

    Ebrahim Ali; Lerman Joshua A; Palsson Bernhard O; Hyduke Daniel R

    BMC systems biology (2013), 7 (), 74 ISSN:.

    BACKGROUND: COnstraint-Based Reconstruction and Analysis (COBRA) methods are widely used for genome-scale modeling of metabolic networks in both prokaryotes and eukaryotes. Due to the successes with metabolism, there is an increasing effort to apply COBRA methods to reconstruct and analyze integrated models of cellular processes. The COBRA Toolbox for MATLAB is a leading software package for genome-scale analysis of metabolism; however, it was not designed to elegantly capture the complexity inherent in integrated biological networks and lacks an integration framework for the multiomics data used in systems biology. The openCOBRA Project is a community effort to promote constraints-based research through the distribution of freely available software. RESULTS: Here, we describe COBRA for Python (COBRApy), a Python package that provides support for basic COBRA methods. COBRApy is designed in an object-oriented fashion that facilitates the representation of the complex biological processes of metabolism and gene expression. COBRApy does not require MATLAB to function; however, it includes an interface to the COBRA Toolbox for MATLAB to facilitate use of legacy codes. For improved performance, COBRApy includes parallel processing support for computationally intensive processes. CONCLUSION: COBRApy is an object-oriented framework designed to meet the computational challenges associated with the next generation of stoichiometric constraint-based models and high-density omics data sets. AVAILABILITY: http://opencobra.sourceforge.net/

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3sfnvFKjuw%253D%253D&md5=77a44dd92f904bf441e4377fb479848e
35. 35

    Caligiuri, M. G.; Bauerle, R. Subunit Communication in the Anthranilate Synthase Complex from Salmonella typhimurium. Science 1991, 252, 1845– 1848,  DOI: 10.1126/science.2063197

    Google Scholar

    35

    Subunit communication in the anthranilate synthase complex from Salmonella typhimurium

    Caligiuri, Maureen G.; Bauerle, Ronald

    Science (Washington, DC, United States) (1991), 252 (5014), 1845-8CODEN: SCIEAS; ISSN:0036-8075.

    The anthranilate synthase-phosphoribosyl transferase complex of the tryptophan biosynthetic pathway in S. typhimurium is an allosteric, heterotetrameric (TrpE2-TrpD2) enzyme whose multiple activities are neg. feedback-regulated by L-tryptophan. A hybrid complex contg. one catalytically active, feedback-insensitive and one catalytically inactive, feedback-sensitive mutant TrpE subunit was assembled in vitro and used to investigate communication between regulatory and catalytic sites located on different subunits. The properties of the hybrid complex demonstrate that the binding of a single inhibitor mol. to one TrpE subunit is sufficient for the propagation of a conformational change that affects the active site of the companion subunit.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3MXlsFers7g%253D&md5=eeed0e78240049536894d9099399809b
36. 36

    Gaspari, E.; Koehorst, J. J.; Frey, J.; Martins Dos Santos, V. A. P.; Suarez-Diez, M. Galactocerebroside Biosynthesis Pathways of Mycoplasma Species: an Antigen Triggering Guillain-Barré-Stohl Syndrome. Microb. Biotechnol. 2021, 14, 1201– 1211,  DOI: 10.1111/1751-7915.13794

    Google Scholar

    36

    Galactocerebroside biosynthesis pathways of Mycoplasma species: an antigen triggering Guillain-Barre-Stohl syndrome

    Gaspari, Erika; Koehorst, Jasper J.; Frey, Joachim; Martins dos Santos, Vitor A. P.; Suarez-Diez, Maria

    Microbial Biotechnology (2021), 14 (3), 1201-1211CODEN: MBIIB2; ISSN:1751-7915. (Wiley-Blackwell)

    Infection by Mycoplasma pneumoniae has been identified as a preceding factor of Guillain-Barre-Stohl syndrome. The Guillain-Barre-Stohl syndrome is triggered by an immune reaction against the major glycolipids and it has been postulated that M. pneumoniae infection triggers this syndrome due to bacterial prodn. of galactocerebroside. Here, we present an extensive comparison of 224 genome sequences from 104 Mycoplasma species to characterize the genetic determinants of galactocerebroside biosynthesis. Hidden Markov models were used to analyze glycosil transferases, leading to identification of a functional protein domain, termed M2000535 that appears in about a third of the studied genomes. This domain appears to be assocd. with a potential UDP-glucose epimerase, which converts UDP-glucose into UDP-galactose, a main substrate for the biosynthesis of galactocerebroside. These findings clarify the pathogenic mechanisms underlining the triggering of Guillain-Barre-Stohl syndrome by M. pneumoniae infections.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXpvFGjtrc%253D&md5=25b30f57b4f7a2feb1df22a754057e67
37. 37

    Kulik, V.; Hartmann, E.; Weyand, M.; Frey, M.; Gierl, A.; Niks, D.; Dunn, M. F.; Schlichting, I. On the Structural Basis of the Catalytic Mechanism and the Regulation of the Alpha Subunit of Tryptophan Synthase from Salmonella typhimurium and BX1 from Maize, Two Evolutionary Related Enzymes. J. Mol. Biol. 2005, 352, 608– 620,  DOI: 10.1016/j.jmb.2005.07.014

    Google Scholar

    37

    On the Structural Basis of the Catalytic Mechanism and the Regulation of the Alpha Subunit of Tryptophan Synthase from Salmonella typhimurium and BX1 from Maize, Two Evolutionarily Related Enzymes

    Kulik, Victor; Hartmann, Elisabeth; Weyand, Michael; Frey, Monika; Gierl, Alfons; Niks, Dimitri; Dunn, Michael F.; Schlichting, Ilme

    Journal of Molecular Biology (2005), 352 (3), 608-620CODEN: JMOBAK; ISSN:0022-2836. (Elsevier B.V.)

    Indole is a reaction intermediate in at least two biosynthetic pathways in maize seedlings. In the primary metab., the α-subunit (TSA) of the bifunctional tryptophan synthase (TRPS) catalyzes the cleavage of indole 3-glycerol phosphate (IGP) to indole and D-glyceraldehyde 3-phosphate (G3P). Subsequently, indole diffuses through the connecting tunnel to the β-active site where it is condensed with serine to form tryptophan and water. The maize enzyme, BX1, a homolog of TSA, also cleaves IGP to G3P and indole, and the indole is further converted to 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one, a secondary plant metabolite. BX1 cleaves IGP significantly faster to G3P and indole than does TSA. In line with their different biol. functions, these two evolutionary related enzymes differ significantly in their regulatory aspects while catalyzing the same chem. Here, the mechanism of IGP cleavage by TSA was analyzed using a novel transition state analog generated in situ by reaction of 2-aminophenol and G3P. The crystal structure of the complex shows an Sp3-hybridized atom corresponding to the C3 position of IGP. The catalytic αGlu49 rotates to interact with the Sp3-hybridized atom and the 3' hydroxyl group suggesting that it serves both as proton donor and acceptor in the α-reaction. The second catalytic residue, αAsp60 interacts with the atom corresponding to the indolyl nitrogen, and the catalytically important loop αL6 is in the closed, high activity conformation. Comparison of the TSA and TSA-transition state analog structures with the crystal structure of BX1 suggests that the faster catalytic rate of BX1 may be due to a stabilization of the active conformation: loop αL6 is closed and the catalytic glutamate is in the active conformation. The latter is caused by a substitution of the residues that stabilize the inactive conformation in TRPS.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXpslyltbY%253D&md5=75f91ec00d38b324d1ba1ca33f39723b
38. 38

    Tamir, H.; Srinivasan, P. R. Studies of the Mechanism of Anthranilate Synthase Reaction. Proc. Natl. Acad. Sci. U.S.A. 1970, 66, 547– 551,  DOI: 10.1073/pnas.66.2.547

    Google Scholar

    38

    Mechanism of anthranilate synthase reaction

    Tamir, Hadassah; Srinivasan, Parithychery R.

    Proceedings of the National Academy of Sciences of the United States of America (1970), 66 (2), 547-51CODEN: PNASA6; ISSN:0027-8424.

    The enzyme anthranilate synthase catalyzes the formation of anthranilate from either chorismate and glutamine or chorismate and ammonia. In the aromatization of chorismate, a hydroxyl group and an enolpyruvyl group must be eliminated. Elimination of the enolpyruvyl group of chorismate is accompanied by protonation to form pyruvate. The source of this proton was investigated by performing the enzymic reaction in 99.7% D2O. The isolated pyruvate contained close to an atom of deuterium in the Me group. High resolution mass spectra also revealed that ∼6% of the deuterio pyruvate contains a CHD2 species. Thus, the results obtained conclusively demonstrate that in the formation of the pyruvate, the 3rd H+ of the Me group arises from water and not by intramol. shift of a H+ from the ring of chorismate.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE3cXkslehu7Y%253D&md5=3e4a0062ed02d654c1266f3422830578
39. 39

    Jakoby, M.; Tesch, M.; Sahm, H.; Krämer, R.; Burkovski, A. Isolation of the Corynebacterium glutamicum glnA Gene Encoding Glutamine Synthetase I. FEMS Microbiol. Lett. 2006, 154, 81– 88,  DOI: 10.1111/j.1574-6968.1997.tb12627.x

    Google Scholar

    There is no corresponding record for this reference.
40. 40

    Lubitz, D.; Wendisch, V. F. Ciprofloxacin Triggered Glutamate Production by Corynebacterium glutamicum. BMC Microbiol. 2016, 16, 235  DOI: 10.1186/s12866-016-0857-6

    Google Scholar

    40

    Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum

    Lubitz, Dorit; Wendisch, Volker F.

    BMC Microbiology (2016), 16 (), 235/1-235/12CODEN: BMMIBC; ISSN:1471-2180. (BioMed Central Ltd.)

    Corynebacterium glutamicum is a well-studied bacterium which naturally overproduces glutamate when induced by an elicitor. Glutamate prodn. is accompanied by decreased 2-oxoglutatate dehydrogenase activity. Elicitors of glutamate prodn. by C. glutamicum analyzed to mol. detail target the cell envelope. Ciprofloxacin, an inhibitor of bacterial DNA gyrase and topoisomerase IV, was shown to inhibit growth of C. glutamicum wild type with concomitant excretion of glutamate. Enzyme assays showed that 2-oxoglutarate dehydrogenase activity was decreased due to ciprofloxacin addn. Transcriptome anal. revealed that this inhibitor of DNA gyrase increased RNA levels of genes involved in DNA synthesis, repair and modification. Glutamate prodn. triggered by ciprofloxacin led to glutamate titers of up to 37 ± 1 mM and a substrate specific glutamate yield of 0.13 g/g. Even in the absence of the putative glutamate exporter gene yggB, ciprofloxacin effectively triggered glutamate prodn. When C. glutamicum wild type was cultivated under nitrogen-limiting conditions, 2-oxoglutarate rather than glutamate was produced as consequence of exposure to ciprofloxacin. Recombinant C. glutamicum strains overproducing lysine, arginine, ornithine, and putrescine, resp., secreted glutamate instead of the desired amino acid when exposed to ciprofloxacin. Ciprofloxacin induced DNA synthesis and repair genes, reduced 2-oxoglutarate dehydrogenase activity and elicited glutamate prodn. by C. glutamicum. Prodn. of 2-oxoglutarate could be triggered by ciprofloxacin under nitrogen-limiting conditions.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsFWisbY%253D&md5=a38fb28f81e0992fd5aaa50f4ad8a7b3
41. 41

    Nakamura, J.; Hirano, S.; Ito, H.; Wachi, M. Mutations of the Corynebacterium glutamicum NCgl1221 Gene, Encoding a Mechanosensitive Channel Homolog, Induce L-Glutamic Acid Production. Appl. Environ. Microbiol. 2007, 73, 4491– 4498,  DOI: 10.1128/AEM.02446-06

    Google Scholar

    41

    Mutations of the Corynebacterium glutamicum NCgl1221 gene, encoding a mechanosensitive channel homolog, induce L-glutamic acid production

    Nakamura, Jun; Hirano, Seiko; Ito, Hisao; Wachi, Masaaki

    Applied and Environmental Microbiology (2007), 73 (14), 4491-4498CODEN: AEMIDF; ISSN:0099-2240. (American Society for Microbiology)

    Corynebacterium glutamicum is a biotin auxotroph that secretes L-glutamic acid in response to biotin limitation; this process is employed in industrial L-glutamic acid prodn. Fatty acid ester surfactants and penicillin also induce L-glutamic acid secretion, even in the presence of biotin. However, the mechanism of L-glutamic acid secretion remains unclear. It was recently reported that disruption of odhA, encoding a subunit of the 2-oxoglutarate dehydrogenase complex, resulted in L-glutamic acid secretion without induction. In this study, we analyzed odhA disruptants and found that those which exhibited constitutive L-glutamic acid secretion carried addnl. mutations in the NCgl1221 gene, which encodes a mechanosensitive channel homolog. These NCgl1221 gene mutations lead to constitutive L-glutamic acid secretion even in the absence of odhA disruption and also render cells resistant to an L-glutamic acid analog, 4-fluoroglutamic acid. Disruption of the NCgl1221 gene essentially abolishes L-glutamic acid secretion, causing an increase in the intracellular L-glutamic acid pool under biotin-limiting conditions, while amplification of the wild-type NCgl1221 gene increased L-glutamate secretion, although only in response to induction. These results suggest that the NCgl1221 gene encodes an L-glutamic acid exporter. We propose that treatments that induce L-glutamic acid secretion alter membrane tension and trigger a structural transformation of the NCgl1221 protein, enabling it to export L-glutamic acid.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXot1egsrg%253D&md5=87f3aa6f53042c708dc6b2ca798fe099
42. 42

    Syukur Purwanto, H.; Kang, M.-S.; Ferrer, L.; Han, S. S.; Lee, J. Y.; Kim, H. S.; Lee, J. H. Rational Engineering of the Shikimate and Related Pathways in Corynebacterium glutamicum for 4-Hydroxybenzoate Production. J. Biotechnol. 2018, 282, 92– 100,  DOI: 10.1016/j.jbiotec.2018.07.016

    Google Scholar

    42

    Rational engineering of the shikimate and related pathways in Corynebacterium glutamicum for 4-hydroxybenzoate production

    Syukur Purwanto, Henry; Kang, Mi-Sook; Ferrer, Lenny; Han, Sang-Soo; Lee, Jin-Young; Kim, Hak-Sung; Lee, Jin-Ho

    Journal of Biotechnology (2018), 282 (), 92-100CODEN: JBITD4; ISSN:0168-1656. (Elsevier B.V.)

    4-Hydroxybenzoate (4HBA) is a valuable platform intermediate for the prodn. of commodity and fine chems., including protocatechuate, cis,cis-muconic acid, adipic acid, terephthalic acid, phenol, vanillin, and 4-hydroxybenzyl alc. glycoside (gastrodin). Here we describe rational engineering of the shikimate and related pathways in Corynebacterium glutamicum ATCC13032 for over-producing 4HBA. As an approach to increase the carbon flux to 4HBA, we first introduced a mutated chorismate-pyruvate lyase (CPLpr) and feedback-resistant 3-deoxy-D-arabinoheptulosonate-7-phosphate synthases encoded by ubiCpr and aroFfbr/aroGfbr, resp., from Escherichia coli along with blockage of carbon flux to the biosynthetic pathways for arom. amino acids and the catabolic pathway for 4HBA by deletion of the genes trpE (encoding anthranilate synthase I), csm (chorismate mutase), and pobA (4HBA hydroxylase). In particular, CPLpr less sensitive to product inhibition was incorporated into the microorganism to enhance the conversion of chorismate to 4HBA. The subsequent steps involved expression of aroE (shikimate kinase) and aroCKB in the shikimate pathway and deletion of qsuABD coding for enzymes involved in the quinate/shikimate degrdn. pathway. Finally, to reduce accumulation of pathway intermediates, shikimate and 3-dehydroshikimate, shikimate-resistant AroK from Methanocaldococcus jannaschii was introduced. The resulting strain was shown to produce 19.0 g/L (137.6 mM) of 4HBA with a molar yield of 9.65% after 65 h in a fed-batch fermn. The engineered strain can also be effectively applied for the prodn. of other products derived from the shikimate pathway.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXhsVShtrbE&md5=a7db9c50ee8aaa60e8e58c129f950b3f
43. 43

    Anbarasan, P.; Baer, Z. C.; Sreekumar, S.; Gross, E.; Binder, J. B.; Blanch, H. W.; Clark, D. S.; Dean Toste, F. Integration of Chemical Catalysis with Extractive Fermentation to Produce Fuels. Nature 2012, 491, 235– 239,  DOI: 10.1038/nature11594

    Google Scholar

    43

    Integration of chemical catalysis with extractive fermentation to produce fuels

    Anbarasan, Pazhamalai; Baer, Zachary C.; Sreekumar, Sanil; Gross, Elad; Binder, Joseph B.; Blanch, Harvey W.; Clark, Douglas S.; Toste, F. Dean

    Nature (London, United Kingdom) (2012), 491 (7423), 235-239CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)

    Nearly one hundred years ago, the fermentative prodn. of acetone by Clostridium acetobutylicum provided a crucial alternative source of this solvent for manuf. of the explosive cordite. Today there is a resurgence of interest in solventogenic Clostridium species to produce n-butanol and ethanol for use as renewable alternative transportation fuels. Acetone, a product of acetone-n-butanol-ethanol (ABE) fermn., harbours a nucleophilic α-carbon, which is amenable to C-C bond formation with the electrophilic alcs. produced in ABE fermn. This functionality can be used to form higher-mol.-mass hydrocarbons similar to those found in current jet and diesel fuels. Here we describe the integration of biol. and chemocatalytic routes to convert ABE fermn. products efficiently into ketones by a palladium-catalyzed alkylation. Tuning of the reaction conditions permits the prodn. of either petrol or jet and diesel precursors. Glyceryl tributyrate was used for the in situ selective extn. of both acetone and alcs. to enable the simple integration of ABE fermn. and chem. catalysis, while reducing the energy demand of the overall process. This process provides a means to selectively produce petrol, jet and diesel blend stocks from lignocellulosic and cane sugars at yields near their theor. maxima.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhs1eltL3N&md5=9addaf38aca49ca52c6cf7226caa79f4
44. 44

    Murdock, D.; Ensley, B. D.; Serdar, C.; Thalen, M. Construction of Metabolic Operons Catalyzing the De novo Biosynthesis of Indigo in Escherichia coli. Nat. Biotechnol. 1993, 11, 381– 386,  DOI: 10.1038/nbt0393-381

    Google Scholar

    There is no corresponding record for this reference.
45. 45

    Ikeda, M.; Nakanishi, K.; Kino, K.; Katsumata, R. Fermentative Production of Tryptophan by a Stable Recombinant Strain of Corynebacterium glutamicum with a Modified Serine-biosynthetic Pathway. Biosci., Biotechnol., Biochem. 1994, 58, 674– 678,  DOI: 10.1271/bbb.58.674

    Google Scholar

    45

    Fermentative production of tryptophan by a stable recombinant strain of Corynebacterium glutamicum with a modified serine-biosynthetic pathway

    Ikeda, Masato; Nakanishi, Keiko; Kino, Kuniki; Katsumata, Ryoichi

    Bioscience, Biotechnology, and Biochemistry (1994), 58 (4), 674-8CODEN: BBBIEJ; ISSN:0916-8451.

    Introduction of plasmid pKW99, which coexpresses the deregulated 3-deoxy-D-arabinoheptulosonate 7-phosphate synthase and tryptophan-biosynthetic enzymes, into tryptophan-producing C. glutamicum KY10894 resulted in a marked increase (54%) in yield of tryptophan (43 g/L), but incurred 2 problems. One was a decline in sugar consumption at the late stage of fermn. and the other was loss of the plasmid in the absence of selective pressure. The retarded sugar assimilation was attributable to the death of cells that arose from the detrimental action of indole, the last intermediate in the tryptophan pathway, which accumulated as a byproduct. These events simultaneously disappeared when serine, the other substrate of the final reaction by tryptophan synthase, was added. These results indicated that a limiting supply of serine was the cause of the decline in the sugar consumption. Thus, to increase C flux into serine, the gene for 3-phosphoglycerate dehydrogenase (PGD), the 1st enzyme in the serine pathway, was cloned from wild-type C. glutamicum ATCC 31833 and joined to pKW99 to generate pKW9901. Strain KY10894 transformed with pKW9901 favorably consumed sugar through fermn. while accumulating little indole. On the basis of the observation that serine in the medium was consumed rapidly by the recombinant cells, a unique plasmid stabilization system composed of KY9218 (a PGD-deficient serine-requiring strain of KY10894) and pKW9901 was developed. In its combination, cells lacking the plasmid should not proliferate in fermn. media lacking serine. Even if selective pressure was not applied, the modified strain KY9218 with pKW9901 stably maintained the plasmid during fermn. and produced 50 g/L of tryptophan in a 61% increased yield relative to strain KY10894.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXjt1Wnsrc%253D&md5=cdb89946e3999b8f8e2aaa2c5018946f
46. 46

    Walter, T.; Veldmann, K. H.; Götker, S.; Busche, T.; Rückert, C.; Kashkooli, A. B.; Paulus, J.; Cankar, K.; Wendisch, V. F. Physiological Response of Corynebacterium glutamicum to Indole. Microorganisms 2020, 8, 1945  DOI: 10.3390/microorganisms8121945

    Google Scholar

    46

    Physiological response of Corynebacterium glutamicum to indole

    Walter, Tatjana; Veldmann, Kareen H.; Goetker, Susanne; Busche, Tobias; Rueckert, Christian; Kashkooli, Arman Beyraghdar; Paulus, Jannik; Cankar, Katarina; Wendisch, Volker F.

    Microorganisms (2020), 8 (12), 1945CODEN: MICRKN; ISSN:2076-2607. (MDPI AG)

    The arom. heterocyclic compd. indole is widely spread in nature. Due to its floral odor indole finds application in dairy, flavor, and fragrance products. Indole is an inter- and intracellular signaling mol. influencing cell division, sporulation, or virulence in some bacteria that synthesize it from tryptophan by tryptophanase. Corynebacterium glutamicum that is used for the industrial prodn. of amino acids including tryptophan lacks tryptophanase. To test if indole is metabolized by C. glutamicum or has a regulatory role, the physiol. response to indole by this bacterium was studied. As shown by RNAseq anal., indole, which inhibited growth at low concns., increased expression of genes involved in the metab. of iron, copper, and arom. compds. In part, this may be due to iron redn. as indole was shown to reduce Fe3+ to Fe2+ in the culture medium. Mutants with improved tolerance to indole were selected by adaptive lab. evolution. Among the mutations identified by genome sequencing, mutations in three transcriptional regulator genes were demonstrated to be causal for increased indole tolerance. These code for the regulator of iron homeostasis DtxR, the regulator of oxidative stress response RosR, and the hitherto uncharacterized Cg3388. Gel mobility shift anal. revealed that Cg3388 binds to the intergenic region between its own gene and the iolT2-rhcM2D2 operon encoding inositol uptake system IolT2, maleylacetate reductase, and catechol 1,2-dioxygenase. Increased RNA levels of rhcM2 in a cg3388 deletion strain indicated that Cg3388 acts as repressor. Indole, hydroquinone, and 1,2,4-trihydroxybenzene may function as inducers of the iolT2-rhcM2D2 operon in vivo as they interfered with DNA binding of Cg3388 at physiol. concns. in vitro.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXovVSrsb4%253D&md5=a9c1a6b4efd7bf29225b0d8122dc05a0
47. 47

    Weischat, W. O.; Kirschner, K. The Mechanism of the Synthesis of Indoleglycerol Phosphate Catalyzed by Tryptophan Synthase from Escherichia coli. Eur. J. Biochem. 1976, 65, 365– 373,  DOI: 10.1111/j.1432-1033.1976.tb10350.x

    Google Scholar

    There is no corresponding record for this reference.
48. 48

    Kishore, N.; Tewari, Y. B.; Akers, D. L.; Goldberg, R. N.; Wilson Miles, E. A Thermodynamic Investigation of Reactions Catalyzed by Tryptophan Synthase. Biophys. Chem. 1998, 73, 265– 280,  DOI: 10.1016/S0301-4622(98)00151-3

    Google Scholar

    48

    A thermodynamic investigation of reactions catalyzed by tryptophan synthase

    Kishore, Nand; Tewari, Yadu B.; Akers, David L.; Goldberg, Robert N.; Miles, Edith Wilson

    Biophysical Chemistry (1998), 73 (3), 265-280CODEN: BICIAZ; ISSN:0301-4622. (Elsevier Science B.V.)

    Microcalorimetry and high-performance liq. chromatog. have been used to conduct a thermodn. investigation of the following reactions catalyzed by the tryptophan synthase α2β2 complex (EC 4.2.1.20) and its subunits: indole(aq.) + L-serine(aq.) = L-tryptophan(aq.) + H2O(liq.), L-serine(aq.) = pyruvate(aq.) + ammonia(aq.), indole(aq.) + D-glyceraldehyde 3-phosphate(aq.) = 1-(indol-3-yl)glycerol 3-phosphate(aq.), L-serine(aq.) + 1-(indol-3-yl)glycerol 3-phosphate(aq.) = L-tryptophan(aq.) + D-glyceraldehyde 3-phosphate(aq.) + H2O(liq.). The calorimetric measurements led to std. molar enthalpy changes for all four of these reactions. Direct measurements yielded an apparent equil. const. for the third reaction; equil. consts. for the remaining three reactions were obtained by using thermochem. cycle calcns. The results of the calorimetric and equil. measurements were analyzed in terms of a chem. equil. model that accounted for the multiplicity of the ionic states of the reactants and products. Thermodn. quantities for chem. ref. reactions involving specific ionic forms have been obtained. These quantities permit the calcn. of the position of equil. of the above four reactions as a function of temp., pH, and ionic strength. Values of the apparent equil. consts. and std. transformed Gibbs free energy changes ΔrGm° under approx. physiol. conditions are given. Le Chatelier's principle provides an explanation as to why, in the metabolic pathway leading to the synthesis of L-tryptophan, the third reaction proceeds in the direction of formation of indole and D-glyceraldehyde 3-phosphate even though the apparent equil. const. greatly favors the formation of 1-(indol-3-yl)glycerol 3-phosphate.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXktFGntLo%253D&md5=ace89ef8b1e42eac6adf948582b1d9c9
49. 49

    Axe, J. M.; O'Rourke, K. F.; Kerstetter, N. E.; Yezdimer, E. M.; Chan, Y. M.; Chasin, A.; Boehr, D. D. Severing of a Hydrogen Bond Disrupts Amino Acid Networks in the Catalytically Active State of the Alpha Subunit of Tryptophan Synthase. Protein Sci. 2015, 24, 484– 494,  DOI: 10.1002/pro.2598

    Google Scholar

    49

    Severing of a hydrogen bond disrupts amino acid networks in the catalytically active state of the alpha subunit of tryptophan synthase

    Axe, Jennifer M.; O'Rourke, Kathleen F.; Kerstetter, Nicole E.; Yezdimer, Eric M.; Chan, Yan M.; Chasin, Alexander; Boehr, David D.

    Protein Science (2015), 24 (4), 484-494CODEN: PRCIEI; ISSN:1469-896X. (Wiley-Blackwell)

    Conformational changes in the β2α2 and β6α6 loops in the alpha subunit of tryptophan synthase (αTS) are important for enzyme catalysis and coordinating substrate channeling with the beta subunit (βTS). It was previously shown that disrupting the hydrogen bond interactions between these loops through the T183V substitution on the β6α6 loop decreases catalytic efficiency and impairs substrate channeling. Results presented here also indicate that the T183V substitution decreases catalytic efficiency in Escherichia coli αTS in the absence of the βTS subunit. NMR expts. indicate that the T183V substitution leads to local changes in the structural dynamics of the β2α2 and β6α6 loops. We have also used NMR chem. shift covariance analyses (CHESCA) to map amino acid networks in the presence and absence of the T183V substitution. Under conditions of active catalytic turnover, the T183V substitution disrupts long-range networks connecting the catalytic residue Glu49 to the αTS-βTS binding interface, which might be important in the coordination of catalytic activities in the tryptophan synthase complex. The approach that we have developed here will likely find general utility in understanding long-range impacts on protein structure and dynamics of amino acid substitutions generated through protein engineering and directed evolution approaches, and provide insight into disease and drug-resistance mutations.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXkvVOqtrk%253D&md5=70b4e8820749bf81e975451099dcba69
50. 50

    Lambrecht, J. A.; Downs, D. M. Anthranilate Phosphoribosyl Transferase (TrpD) Generates Phosphoribosylamine for Thiamine Synthesis from Enamines and Phosphoribosyl Pyrophosphate. ACS Chem. Biol. 2013, 8, 242– 248,  DOI: 10.1021/cb300364k

    Google Scholar

    50

    Anthranilate phosphoribosyl transferase (TrpD) generates phosphoribosylamine for thiamine synthesis from enamines and phosphoribosyl pyrophosphate

    Lambrecht, Jennifer A.; Downs, Diana M.

    ACS Chemical Biology (2013), 8 (1), 242-248CODEN: ACBCCT; ISSN:1554-8929. (American Chemical Society)

    Anthranilate phosphoribosyltransferase (TrpD) has been well characterized for its role in the tryptophan biosynthetic pathway. Here, the authors characterized a new reaction catalyzed by TrpD that resulted in the formation of the purine/thiamin intermediate metabolite, phosphoribosylamine (PRA). The data showed that 4- and 5-carbon enamines served as substrates for TrpD, and the reaction product was predicted to be a phosphoribosyl-enamine adduct. Isotopic labeling data indicated that the TrpD reaction product was hydrolyzed to PRA. Variants of TrpD that were proficient for tryptophan synthesis were unable to support PRA formation in vivo in Salmonella enterica. These protein variants had substitutions at residues that contributed to binding substrates anthranilate or phosphoribosyl pyrophosphate (PRPP). Taken together the data identified a new reaction catalyzed by a well-characterized biosynthetic enzyme, and both illustrated the robustness of the metabolic network and identified a role for an enamine that accumulates in the absence of reactive intermediate deaminase RidA.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsFOltrnE&md5=0623316e94704ce907fd68e5cc342ac7
51. 51

    Jensen, K. F.; Dandanell, G.; Hove-Jensen, B.; WillemoËs, M. Nucleotides, Nucleosides, and Nucleobases. EcoSal Plus 2008, 3, 1– 39,  DOI: 10.1128/ecosalplus.3.6.2

    Google Scholar

    There is no corresponding record for this reference.
52. 52

    Alderwick, L. J.; Dover, L. G.; Seidel, M.; Gande, R.; Sahm, H.; Eggeling, L.; Besra, G. S. Arabinan-deficient Mutants of Corynebacterium glutamicum and the Consequent Flux in Decaprenylmonophosphoryl-d-arabinose Metabolism. Glycobiology 2006, 16, 1073– 1081,  DOI: 10.1093/GLYCOB/CWL030

    Google Scholar

    52

    Arabinan-deficient mutants of Corynebacterium glutamicum and the consequent flux in decaprenylmonophosphoryl-D-arabinose metabolism

    Alderwick, Luke J.; Dover, Lynn G.; Seidel, Mathias; Gande, Roland; Sahm, Hermann; Eggeling, Lothar; Besra, Gurdyal S.

    Glycobiology (2006), 16 (11), 1073-1081CODEN: GLYCE3; ISSN:0959-6658. (Oxford University Press)

    The arabinogalactan (AG) of Corynebacterianeae is a crit. macromol. that tethers mycolic acids to peptidoglycan, thus forming a highly impermeable cell wall matrix termed the mycolyl-arabinogalactan peptidoglycan complex (mAGP). The front line anti-tuberculosis drug, ethambutol (Emb), targets the Mycobacterium tuberculosis and Corynebacterium glutamicum arabinofuranosyltransferase Mt-EmbA, Mt-EmbB and Cg-Emb enzymes, resp., which are responsible for the biosynthesis of the arabinan domain of AG. The substrate utilized by these important glycosyltransferases, decaprenylmonophosphoryl-D-arabinose (DPA), is synthesized via a decaprenylphosphoryl-5-phosphoribose (DPPR) synthase (UbiA), which catalyzes the transfer of 5-phospho-ribofuranose-pyrophosphate (pRpp) to decaprenol phosphate to form DPPR. Glycosyl compositional anal. of cell walls extd. from a C. glutamicum::ubiA mutant revealed a galactan core consisting of alternating β(1→5)-Galf and β(1→6)-Galf residues, completely devoid of arabinan and a concomitant loss of cell-wall-bound mycolic acids. In addn., in vitro assays demonstrated a complete loss of arabinofuranosyltransferase activity and DPA biosynthesis in the C. glutamicum::ubiA mutant when supplemented with p[14C]Rpp, the precursor of DPA. Interestingly, in vitro arabinofuranosyltransferase activity was restored in the C. glutamicum::ubiA mutant when supplemented with exogenous DP[14C]A substrate, and C. glutamicum strains deficient in ubiA, emb, and aftA all exhibited different levels of DPA biosynthesis.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtVOmurfF&md5=51243823d0073b948a4f54b51674880c
53. 53

    Klyachko, E. V.; Shakulov, R. S.; Kozlov, Y. I. Mutant Phosphoribosylpyrophosphate Synthetase and Method for Producing L-Histidine. European Patent EP1529839A12005.

    Google Scholar

    There is no corresponding record for this reference.
54. 54

    Prell, C.; Busche, T.; Rückert, C.; Nolte, L.; Brandenbusch, C.; Wendisch, V. F. Adaptive Laboratory Evolution Accelerated Glutarate Production by Corynebacterium glutamicum. Microb. Cell Fact. 2021, 20, 97  DOI: 10.1186/s12934-021-01586-3

    Google Scholar

    54

    Adaptive laboratory evolution accelerated glutarate production by Corynebacterium glutamicum

    Prell, Carina; Busche, Tobias; Rueckert, Christian; Nolte, Lea; Brandenbusch, Christoph; Wendisch, Volker F.

    Microbial Cell Factories (2021), 20 (1), 97CODEN: MCFICT; ISSN:1475-2859. (BioMed Central Ltd.)

    The demand for biobased polymers is increasing steadily worldwide. Microbial hosts for prodn. of their monomeric precursors such as glutarate are developed. To meet the market demand, prodn. hosts have to be improved constantly with respect to product titers and yields, but also shortening bioprocess duration is important. In this study, adaptive lab. evolution was used to improve a C. glutamicum strain engineered for prodn. of the C5-dicarboxylic acid glutarate by flux enforcement. Deletion of the L-glutamic acid dehydrogenase gene gdh coupled growth to glutarate prodn. since two transaminases in the glutarate pathway are crucial for nitrogen assimilation. The hypothesis that strains selected for faster glutarate-coupled growth by adaptive lab. evolution show improved glutarate prodn. was tested. A serial diln. growth expt. allowed isolating faster growing mutants with growth rates increasing from 0.10 h-1 by the parental strain to 0.17 h-1 by the fastest mutant. Indeed, the fastest growing mutant produced glutarate with a twofold higher volumetric productivity of 0.18 g L-1 h-1 than the parental strain. Genome sequencing of the evolved strain revealed candidate mutations for improved prodn. Reverse genetic engineering revealed that an amino acid exchange in the large subunit of L-glutamic acid-2-oxoglutarate aminotransferase was causal for accelerated glutarate prodn. and its beneficial effect was dependent on flux enforcement due to deletion of gdh. Performance of the evolved mutant was stable at the 2 L bioreactor-scale operated in batch and fed-batch mode in a mineral salts medium and reached a titer of 22.7 g L-1, a yield of 0.23 g g-1 and a volumetric productivity of 0.35 g L-1 h-1. Reactive extn. of glutarate directly from the fermn. broth was optimized leading to yields of 58% and 99% in the reactive extn. and reactive re-extn. step, resp. The fermn. medium was adapted according to the downstream processing results. Flux enforcement to couple growth to operation of a product biosynthesis pathway provides a basis to select strains growing and producing faster by adaptive lab. evolution. After identifying candidate mutations by genome sequencing causal mutations can be identified by reverse genetics. As exemplified here for glutarate prodn. by C. glutamicum, this approach allowed deducing rational metabolic engineering strategies.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhtF2nsbvJ&md5=b7912b96901d87efc4b1f8ae889c6944
55. 55

    Wendisch, V. F.; Brito, L. F.; Gil Lopez, M.; Hennig, G.; Pfeifenschneider, J.; Sgobba, E.; Veldmann, K. H. The Flexible Feedstock Concept in Industrial Biotechnology: Metabolic Engineering of Escherichia coli, Corynebacterium glutamicum, Pseudomonas, Bacillus and Yeast Strains for Access to Alternative Carbon Sources. J. Biotechnol. 2016, 234, 139– 157,  DOI: 10.1016/j.jbiotec.2016.07.022

    Google Scholar

    55

    The flexible feedstock concept in Industrial Biotechnology: Metabolic engineering of Escherichia coli, Corynebacterium glutamicum, Pseudomonas, Bacillus and yeast strains for access to alternative carbon sources

    Wendisch, Volker F.; Brito, Luciana Fernandes; Gil Lopez, Marina; Hennig, Guido; Pfeifenschneider, Johannes; Sgobba, Elvira; Veldmann, Kareen H.

    Journal of Biotechnology (2016), 234 (), 139-157CODEN: JBITD4; ISSN:0168-1656. (Elsevier B.V.)

    A review. Most biotechnol. processes are based on glucose that is either present in molasses or generated from starch by enzymic hydrolysis. At the very high, million-ton scale prodn. vols., for instance for fermentative prodn. of the biofuel ethanol or of commodity chems. such as org. acids and amino acids, competing uses of carbon sources e.g. in human and animal nutrition have to be taken into account. Thus, the biotechnol. prodn. hosts E. coli, C. glutamicum, pseudomonads, bacilli and baker's yeast used in these large scale processes have been engineered for efficient utilization of alternative carbon sources. This flexible feedstock concept is central to the use of non-glucose second and third generation feedstocks in the emerging bioeconomy. The metabolic engineering efforts to broaden the substrate scope of E. coli, C. glutamicum, pseudomonads, B. subtilis and yeasts to include non-native carbon sources will be reviewed. Strategies to enable simultaneous consumption of mixts. of native and non-native carbon sources present in biomass hydrolyzates will be summarized and a perspective on how to further increase feedstock flexibility for the realization of biorefinery processes will be given.

    >> More from SciFinder ^®

    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtlWjtb7N&md5=7b76afdf901e76e429610d5aaac211e6