ACS Publications. Most Trusted. Most Cited. Most Read
Discovering the Microbial Enzymes Driving Drug Toxicity with Activity-Based Protein Profiling

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:ACS Chem. Biol. 2020, 15, 1, 217-225
    Articles

    Discovering the Microbial Enzymes Driving Drug Toxicity with Activity-Based Protein Profiling
    Click to copy article linkArticle link copied!

    • Parth B. Jariwala
      Parth B. Jariwala
      Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
      More by Parth B. Jariwala
    • Samuel J. Pellock
      Samuel J. Pellock
      Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
      More by Samuel J. Pellock
    • Dennis Goldfarb
      Dennis Goldfarb
      Institute for Informatics  and  Department of Cell Biology and Physiology, Washington University, St. Louis, Missouri 63130, United States
      More by Dennis Goldfarb
    • Erica W. Cloer
      Erica W. Cloer
      Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
      More by Erica W. Cloer
    • Marta Artola
      Marta Artola
      Department of Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden 2311, The Netherlands
      More by Marta Artola
      Orcidhttp://orcid.org/0000-0002-3051-3902
    • Joshua B. Simpson
      Joshua B. Simpson
      Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
      More by Joshua B. Simpson
    • Aadra P. Bhatt
      Aadra P. Bhatt
      Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
      More by Aadra P. Bhatt
    • William G. Walton
      William G. Walton
      Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
      More by William G. Walton
    • Lee R. Roberts
      Lee R. Roberts
      Exploratory Science Center, Merck & Company Inc., Cambridge, Massachusetts 02141, United States
      More by Lee R. Roberts
    • Michael B. Major
      Michael B. Major
      Department of Cell Biology and Physiology  and  Department of Otolaryngology, Washington University, St. Louis, Missouri 63130, United States
      More by Michael B. Major
    • Gideon J. Davies
      Gideon J. Davies
      York Structural Biology Laboratory, Department of Chemistry, University of York, York YO10 5DD, U.K.
      More by Gideon J. Davies
      Orcidhttp://orcid.org/0000-0002-7343-776X
    • Herman S. Overkleeft
      Herman S. Overkleeft
      Department of Bioorganic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden 2311, The Netherlands
      More by Herman S. Overkleeft
    • Matthew R. Redinbo*
      Matthew R. Redinbo
      Department of Chemistry,  Integrated Program for Biological and Genome Sciences  and  Departments of Biochemistry and Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
      *E-mail: [email protected] (M.R.R.).
      More by Matthew R. Redinbo
      Orcidhttp://orcid.org/0000-0003-0814-5346
    Other Access OptionsSupporting Information (6)

    ACS Chemical Biology

    Cite this: ACS Chem. Biol. 2020, 15, 1, 217–225
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acschembio.9b00788
    Published November 27, 2019
    Copyright © 2019 American Chemical Society
    Request reuse permissions

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    It is increasingly clear that interindividual variability in human gut microbial composition contributes to differential drug responses. For example, gastrointestinal (GI) toxicity is not observed in all patients treated with the anticancer drug irinotecan, and it has been suggested that this variability is a result of differences in the types and levels of gut bacterial β-glucuronidases (GUSs). GUS enzymes promote drug toxicity by hydrolyzing the inactive drug–glucuronide conjugate back to the active drug, which damages the GI epithelium. Proteomics-based identification of the exact GUS enzymes responsible for drug reactivation from the complexity of the human microbiota has not been accomplished, however. Here, we discover the specific bacterial GUS enzymes that generate SN-38, the active and toxic metabolite of irinotecan, from human fecal samples using a unique activity-based protein profiling (ABPP) platform. We identify and quantify gut bacterial GUS enzymes from human feces with an ABPP-enabled proteomics pipeline and then integrate this information with ex vivo kinetics to pinpoint the specific GUS enzymes responsible for SN-38 reactivation. Furthermore, the same approach also reveals the molecular basis for differential gut bacterial GUS inhibition observed between human fecal samples. Taken together, this work provides an unprecedented technical and bioinformatics pipeline to discover the microbial enzymes responsible for specific reactions from the complexity of human feces. Identifying such microbial enzymes may lead to precision biomarkers and novel drug targets to advance the promise of personalized medicine.

    Copyright © 2019 American Chemical Society

    Subjects

    what are subjects

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Supporting Information

    Click to copy section linkSection link copied!

    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acschembio.9b00788.

    • Methods and Figures S1–S12 (PDF)

    • Table S1, Crystallographic statistics for B. uniformis GUS-2 bound to the unsubstituted cyclophellitol-based aziridine ABP (2) (XLSX)

    • Table S2, Kinetic parameters for inhibition of select gut bacterial GUS enzymes by cyclophellitol-based inhibitors and ABPs (XLSX)

    • Table S3, Protein groups identified as GUS and compiled loop abundance data (XLSX)

    • Table S4, Taxa annotation for each GUS identified peptide and compiled taxa abundance data (XLSX)

    • Table S5, All protein groups identified (XLSX)

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!
    Citation Statements
    Explore this article's citation statements on scite.ai
    powered by  Scite

    This article is cited by 56 publications.

    1. Md Jalal Uddin, Kjersti Julin, Herman S. Overkleeft, Mona Johannessen, Christian S. Lentz. Activity-Based Protein Profiling Identifies an α-Amylase Family Protein Contributing to the Virulence of Methicillin-Resistant Staphylococcus aureus. ACS Infectious Diseases 2025, 11 (3) , 573-583. https://doi.org/10.1021/acsinfecdis.4c00638
    2. Marta Artola, Johannes M. F. G. Aerts, Gijsbert A. van der Marel, Carme Rovira, Jeroen D. C. Codée, Gideon J. Davies, Herman S. Overkleeft. From Mechanism-Based Retaining Glycosidase Inhibitors to Activity-Based Glycosidase Profiling. Journal of the American Chemical Society 2024, 146 (36) , 24729-24741. https://doi.org/10.1021/jacs.4c08840
    3. Namrata Jain, Kazune Tamura, Guillaume Déjean, Filip Van Petegem, Harry Brumer. Orthogonal Active-Site Labels for Mixed-Linkage endo-β-Glucanases. ACS Chemical Biology 2021, 16 (10) , 1968-1984. https://doi.org/10.1021/acschembio.1c00063
    4. Kathrin Fenner, Martin Elsner, Tillmann Lueders, Michael S. McLachlan, Lawrence P. Wackett, Michael Zimmermann, Jörg E. Drewes. Methodological Advances to Study Contaminant Biotransformation: New Prospects for Understanding and Reducing Environmental Persistence?. ACS ES&T Water 2021, 1 (7) , 1541-1554. https://doi.org/10.1021/acsestwater.1c00025
    5. Punsaldulam Dashnyam, Hsien-Ya Lin, Chia-Yu Chen, Shijay Gao, Lun-Fu Yeh, Wei-Che Hsieh, Zhijay Tu, Chun-Hung Lin. Substituent Position of Iminocyclitols Determines the Potency and Selectivity for Gut Microbial Xenobiotic-Reactivating Enzymes. Journal of Medicinal Chemistry 2020, 63 (9) , 4617-4627. https://doi.org/10.1021/acs.jmedchem.9b01918
    6. Christopher Whidbey. The right tool for the job: Chemical biology and microbiome science. Cell Chemical Biology 2025, 32 (1) , 83-97. https://doi.org/10.1016/j.chembiol.2024.12.004
    7. Deniz Coskuner, Aadra Prashant Bhatt. Phase IV Metabolism. Gastroenterology Clinics of North America 2025, 67 https://doi.org/10.1016/j.gtc.2024.11.004
    8. Jianbing Jiang, Diana Czuchry, Yanxia Ru, Huipai Peng, Junfeng Shen, Teng Wang, Wenjuan Zhao, Weihua Chen, Sen-Fang Sui, Yaowang Li, Nan Li. Activity-based metaproteomics driven discovery and enzymological characterization of potential α-galactosidases in the mouse gut microbiome. Communications Chemistry 2024, 7 (1) https://doi.org/10.1038/s42004-024-01273-5
    9. Yue Han, Yu-Tong Liu, Lu Chen, Hao-Fan Sun, Guang-Hao Zhu, Dong-Ning Kang, Qi Zhou, Hui Tang, Yu-Ling Yin, Jie Hou. Hinokiflavone from Platycladi cacumen as a potent broad-spectrum inhibitor of gut microbial Loop-1 β-glucuronidases: Inhibition kinetics and molecular simulation. Chemico-Biological Interactions 2024, 404 , 111261. https://doi.org/10.1016/j.cbi.2024.111261
    10. Ruiyang Gao, Bei Yue, Cheng Lv, Xiaolong Geng, Zhilun Yu, Hao Wang, Beibei Zhang, Fangbin Ai, Ziyi Wang, Donghui Liu, Zhengtao Wang, Kaixian Chen, Wei Dou. Targeted inhibition of Gus-expressing Enterococcus faecalis to promote intestinal stem cell and epithelial renovation contributes to the relief of irinotecan chemotoxicity by dehydrodiisoeugenol. Acta Pharmaceutica Sinica B 2024, 14 (12) , 5286-5304. https://doi.org/10.1016/j.apsb.2024.09.018
    11. Lars E. Hillege, Milou A. M. Stevens, Paulien A. J. Kristen, Judith de Vos-Geelen, John Penders, Matthew R. Redinbo, Marjolein L. Smidt. The role of gut microbial β-glucuronidases in carcinogenesis and cancer treatment: a scoping review. Journal of Cancer Research and Clinical Oncology 2024, 150 (11) https://doi.org/10.1007/s00432-024-06028-2
    12. Markus Lakemeyer, Julian Seidel. Funktionelle Charakterisierung der Darmflora und ihrerhydrolytisch aktiven Enzyme ‐Trendbericht Biochemie 2024 (2/3). Nachrichten aus der Chemie 2024, 72 (7-8) , 59-62. https://doi.org/10.1002/nadc.20244143493
    13. Joshua B. Simpson, Morgan E. Walker, Joshua J. Sekela, Samantha M. Ivey, Parth B. Jariwala, Cameron M. Storch, Mark E. Kowalewski, Amanda L. Graboski, Adam D. Lietzan, William G. Walton, Kacey A. Davis, Erica W. Cloer, Valentina Borlandelli, Yun-Chung Hsiao, Lee R. Roberts, David H. Perlman, Xue Liang, Hermen S. Overkleeft, Aadra P. Bhatt, Kun Lu, Matthew R. Redinbo. Gut microbial β-glucuronidases influence endobiotic homeostasis and are modulated by diverse therapeutics. Cell Host & Microbe 2024, 32 (6) , 925-944.e10. https://doi.org/10.1016/j.chom.2024.04.018
    14. Lu Chen, Xu-Dong Hou, Guang-Hao Zhu, Jian Huang, Zhao-Bin Guo, Ya-Ni Zhang, Jian-Ming Sun, Li-Juan Ma, Shou-De Zhang, Jie Hou, Guang-Bo Ge. Discovery of a botanical compound as a broad-spectrum inhibitor against gut microbial β-glucuronidases from the Tibetan medicine Rhodiola crenulata. International Journal of Biological Macromolecules 2024, 267 , 131150. https://doi.org/10.1016/j.ijbiomac.2024.131150
    15. Jianling Tan, Bingxuan Fu, Xiaojie Zhao, Ling Ye. Novel Techniques and Models for Studying the Role of the Gut Microbiota in Drug Metabolism. European Journal of Drug Metabolism and Pharmacokinetics 2024, 49 (2) , 131-147. https://doi.org/10.1007/s13318-023-00874-0
    16. Andrew A. Verdegaal, Andrew L. Goodman. Integrating the gut microbiome and pharmacology. Science Translational Medicine 2024, 16 (732) https://doi.org/10.1126/scitranslmed.adg8357
    17. Amanda L. Graboski, Joshua B. Simpson, Samuel J. Pellock, Naimee Mehta, Benjamin C. Creekmore, Yamuna Ariyarathna, Aadra P. Bhatt, Parth B. Jariwala, Josh J. Sekela, Mark E. Kowalewski, Natalie K. Barker, Angie L. Mordant, Valentina B. Borlandelli, Hermen Overkleeft, Laura E. Herring, Jian Jin, Lindsey I. James, Matthew R. Redinbo. Advanced piperazine-containing inhibitors target microbial β-glucuronidases linked to gut toxicity. RSC Chemical Biology 2024, 377 https://doi.org/10.1039/D4CB00058G
    18. Joshua B. Simpson, Josh J. Sekela, Benjamin S. Carry, Violet Beaty, Shakshi Patel, Matthew. R. Redinbo. Diverse but desolate landscape of gut microbial azoreductases: A rationale for idiopathic IBD drug response. Gut Microbes 2023, 15 (1) https://doi.org/10.1080/19490976.2023.2203963
    19. Sander van Kasteren, Daniel E Rozen. Using click chemistry to study microbial ecology and evolution. ISME Communications 2023, 3 (1) https://doi.org/10.1038/s43705-022-00205-5
    20. Sandica Bucurica, Mihaela Lupanciuc, Florentina Ionita-Radu, Ion Stefan, Alice Elena Munteanu, Daniela Anghel, Mariana Jinga, Elena Laura Gaman. Estrobolome and Hepatocellular Adenomas—Connecting the Dots of the Gut Microbial β-Glucuronidase Pathway as a Metabolic Link. International Journal of Molecular Sciences 2023, 24 (22) , 16034. https://doi.org/10.3390/ijms242216034
    21. Lin Han, Pamela V. Chang. Activity-based protein profiling in microbes and the gut microbiome. Current Opinion in Chemical Biology 2023, 76 , 102351. https://doi.org/10.1016/j.cbpa.2023.102351
    22. Jingwei Cai, Alexis Auster, Sungjoon Cho, Zijuan Lai. Dissecting the human gut microbiome to better decipher drug liability: A once-forgotten organ takes center stage. Journal of Advanced Research 2023, 52 , 171-201. https://doi.org/10.1016/j.jare.2023.07.002
    23. Hannah K. Lembke, Erin E. Carlson. Activity-based probes in pathogenic bacteria: Investigating drug targets and molecule specificity. Current Opinion in Chemical Biology 2023, 76 , 102359. https://doi.org/10.1016/j.cbpa.2023.102359
    24. M. Leonor Fernández-Murga, Fernando Gil-Ortiz, Lucía Serrano-García, Antonio Llombart-Cussac. A New Paradigm in the Relationship between Gut Microbiota and Breast Cancer: β-glucuronidase Enzyme Identified as Potential Therapeutic Target. Pathogens 2023, 12 (9) , 1086. https://doi.org/10.3390/pathogens12091086
    25. Mariia A. Beliaeva, Matthias Wilmanns, Michael Zimmermann. Decipher enzymes from human microbiota for drug discovery and development. Current Opinion in Structural Biology 2023, 80 , 102567. https://doi.org/10.1016/j.sbi.2023.102567
    26. Adam D. Lietzan, Joshua B. Simpson, William G. Walton, Parth B. Jariwala, Yongmei Xu, Marcella H. Boynton, Jian Liu, Matthew R. Redinbo. Microbial β-glucuronidases drive human periodontal disease etiology. Science Advances 2023, 9 (18) https://doi.org/10.1126/sciadv.adg3390
    27. Amelia Y. M. Woo, Miguel A. Aguilar Ramos, Rohan Narayan, Khyle C. Richards-Corke, Michelle L. Wang, Walter J. Sandoval-Espinola, Emily P. Balskus. Targeting the human gut microbiome with small-molecule inhibitors. Nature Reviews Chemistry 2023, 7 (5) , 319-339. https://doi.org/10.1038/s41570-023-00471-4
    28. Kien P. Malarney, Pamela V. Chang. Chemoproteomic Approaches for Unraveling Prokaryotic Biology. Israel Journal of Chemistry 2023, 63 (3-4) https://doi.org/10.1002/ijch.202200076
    29. Aaron T. Wright, LaRae A. Hudson, Whitney L. Garcia. Activity‐Based Protein Profiling – Enabling Phenotyping of Host‐Associated and Environmental Microbiomes. Israel Journal of Chemistry 2023, 63 (3-4) https://doi.org/10.1002/ijch.202200099
    30. Gregory M Pellegrino, Tyler S Browne, Keerthana Sharath, Khaleda A Bari, Sarah J Vancuren, Emma Allen-Vercoe, Gregory B Gloor, David R Edgell. Metabolically-targeted dCas9 expression in bacteria. Nucleic Acids Research 2023, 51 (2) , 982-996. https://doi.org/10.1093/nar/gkac1248
    31. Joshua B. Simpson, Josh J. Sekela, Amanda L. Graboski, Valentina B. Borlandelli, Marissa M. Bivins, Natalie K. Barker, Alicia A. Sorgen, Angie L. Mordant, Rebecca L. Johnson, Aadra P. Bhatt, Anthony A. Fodor, Laura E. Herring, Hermen Overkleeft, John R. Lee, Matthew. R. Redinbo. Metagenomics combined with activity-based proteomics point to gut bacterial enzymes that reactivate mycophenolate. Gut Microbes 2022, 14 (1) https://doi.org/10.1080/19490976.2022.2107289
    32. Joshua B. Simpson, Matthew R. Redinbo. Multi-omic analysis of host-microbial interactions central to the gut-brain axis. Molecular Omics 2022, 18 (10) , 896-907. https://doi.org/10.1039/D2MO00205A
    33. Jianan Zhang, Morgan E. Walker, Katherine Z. Sanidad, Hongna Zhang, Yanshan Liang, Ermin Zhao, Katherine Chacon-Vargas, Vladimir Yeliseyev, Julie Parsonnet, Thomas D. Haggerty, Guangqiang Wang, Joshua B. Simpson, Parth B. Jariwala, Violet V. Beaty, Jun Yang, Haixia Yang, Anand Panigrahy, Lisa M. Minter, Daeyoung Kim, John G. Gibbons, LinShu Liu, Zhengze Li, Hang Xiao, Valentina Borlandelli, Hermen S. Overkleeft, Erica W. Cloer, Michael B. Major, Dennis Goldfarb, Zongwei Cai, Matthew R. Redinbo, Guodong Zhang. Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract. Nature Communications 2022, 13 (1) https://doi.org/10.1038/s41467-021-27762-y
    34. Panpan Wang, Rongrong Wu, Yifei Jia, Puipui Tang, Bin Wei, Qingwen Zhang, Vivien Ya-Fan Wang, Ru Yan. Inhibition and structure-activity relationship of dietary flavones against three Loop 1-type human gut microbial β-glucuronidases. International Journal of Biological Macromolecules 2022, 220 , 1532-1544. https://doi.org/10.1016/j.ijbiomac.2022.09.018
    35. Morgan E. Walker, Joshua B. Simpson, Matthew R. Redinbo. A structural metagenomics pipeline for examining the gut microbiome. Current Opinion in Structural Biology 2022, 75 , 102416. https://doi.org/10.1016/j.sbi.2022.102416
    36. Anna-Lena Mueller, Aranka Brockmueller, Niusha Fahimi, Tahere Ghotbi, Sara Hashemi, Sadaf Sadri, Negar Khorshidi, Ajaikumar B. Kunnumakkara, Mehdi Shakibaei. Bacteria-Mediated Modulatory Strategies for Colorectal Cancer Treatment. Biomedicines 2022, 10 (4) , 832. https://doi.org/10.3390/biomedicines10040832
    37. Francesco Candeliere, Stefano Raimondi, Raffaella Ranieri, Eliana Musmeci, Alfonso Zambon, Alberto Amaretti, Maddalena Rossi. β-Glucuronidase Pattern Predicted From Gut Metagenomes Indicates Potentially Diversified Pharmacomicrobiomics. Frontiers in Microbiology 2022, 13 https://doi.org/10.3389/fmicb.2022.826994
    38. Peter S. Thuy-Boun, Ana Y. Wang, Ana Crissien-Martinez, Janice H. Xu, Sandip Chatterjee, Gregory S. Stupp, Andrew I. Su, Walter J. Coyle, Dennis W. Wolan. Quantitative Metaproteomics and Activity-based Protein Profiling of Patient Fecal Microbiome Identifies Host and Microbial Serine-type Endopeptidase Activity Associated With Ulcerative Colitis. Molecular & Cellular Proteomics 2022, 21 (3) , 100197. https://doi.org/10.1016/j.mcpro.2022.100197
    39. Nicholas G. S. McGregor, Chi-Lin Kuo, Thomas J. M. Beenakker, Chun-Sing Wong, Wendy A. Offen, Zachary Armstrong, Bogdan I. Florea, Jeroen D. C. Codée, Herman S. Overkleeft, Johannes M. F. G. Aerts, Gideon J. Davies. Synthesis of broad-specificity activity-based probes for exo -β-mannosidases. Organic & Biomolecular Chemistry 2022, 20 (4) , 877-886. https://doi.org/10.1039/D1OB02287C
    40. Hui-Ju Chen, Yen-Wenn Liu. The Impacts of Probiotics on Microbiota in Patients With Autism Spectrum Disorder. 2022, 296-319. https://doi.org/10.1016/B978-0-12-819265-8.00101-7
    41. Jing-Xin Li, Yu Wang, Ying Hao, Xiao-Kui Huo, Cheng-Peng Sun, Xiao-Xia Zhao, Jin-Cheng Wang, Jian-Bin Zhang, Jing Ning, Xiang-Ge Tian, Chao Wang, Wen-Yu Zhao, Xia Lv, Ya-Chen Li, Xiao-Chi Ma. Identification of Escherichia coli β-glucuronidase inhibitors from Polygonum cuspidatum Siebold & Zucc.. Brazilian Journal of Pharmaceutical Sciences 2022, 58 https://doi.org/10.1590/s2175-97902022e21394
    42. Bei Yue, Ruiyang Gao, Zhengtao Wang, Wei Dou. Microbiota-Host-Irinotecan Axis: A New Insight Toward Irinotecan Chemotherapy. Frontiers in Cellular and Infection Microbiology 2021, 11 https://doi.org/10.3389/fcimb.2021.710945
    43. Miguel Silva, Valentina Brunner, Markus Tschurtschenthaler. Microbiota and Colorectal Cancer: From Gut to Bedside. Frontiers in Pharmacology 2021, 12 https://doi.org/10.3389/fphar.2021.760280
    44. Yue Sui, Jianming Wu, Jianping Chen. The Role of Gut Microbial β-Glucuronidase in Estrogen Reactivation and Breast Cancer. Frontiers in Cell and Developmental Biology 2021, 9 https://doi.org/10.3389/fcell.2021.631552
    45. Shirley M. Tsunoda, Christopher Gonzales, Alan K. Jarmusch, Jeremiah D. Momper, Joseph D. Ma. Contribution of the Gut Microbiome to Drug Disposition, Pharmacokinetic and Pharmacodynamic Variability. Clinical Pharmacokinetics 2021, 60 (8) , 971-984. https://doi.org/10.1007/s40262-021-01032-y
    46. Panpan Wang, Yifei Jia, Rongrong Wu, Zhiqiang Chen, Ru Yan. Human gut bacterial β-glucuronidase inhibition: An emerging approach to manage medication therapy. Biochemical Pharmacology 2021, 190 , 114566. https://doi.org/10.1016/j.bcp.2021.114566
    47. Md Masud Parvez, Abdul Basit, Parth B. Jariwala, Zsuzsanna Gáborik, Emese Kis, Scott Heyward, Matthew R. Redinbo, Bhagwat Prasad. Quantitative Investigation of Irinotecan Metabolism, Transport, and Gut Microbiome Activation. Drug Metabolism and Disposition 2021, 49 (8) , 683-693. https://doi.org/10.1124/dmd.121.000476
    48. Michael Zimmermann, Kiran Raosaheb Patil, Athanasios Typas, Lisa Maier. Towards a mechanistic understanding of reciprocal drug–microbiome interactions. Molecular Systems Biology 2021, 17 (3) https://doi.org/10.15252/msb.202010116
    49. Moamen M. Elmassry, Sunghwan Kim, Ben Busby, . Predicting drug-metagenome interactions: Variation in the microbial β-glucuronidase level in the human gut metagenomes. PLOS ONE 2021, 16 (1) , e0244876. https://doi.org/10.1371/journal.pone.0244876
    50. Leyuan Li, Daniel Figeys. Proteomics and Metaproteomics Add Functional, Taxonomic and Biomass Dimensions to Modeling the Ecosystem at the Mucosal-luminal Interface. Molecular & Cellular Proteomics 2020, 19 (9) , 1409-1417. https://doi.org/10.1074/mcp.R120.002051
    51. Margaret Alexander, Peter J. Turnbaugh. Deconstructing Mechanisms of Diet-Microbiome-Immune Interactions. Immunity 2020, 53 (2) , 264-276. https://doi.org/10.1016/j.immuni.2020.07.015
    52. Sneha P. Couvillion, Neha Agrawal, Sean M. Colby, Kristoffer R. Brandvold, Thomas O. Metz. Who Is Metabolizing What? Discovering Novel Biomolecules in the Microbiome and the Organisms Who Make Them. Frontiers in Cellular and Infection Microbiology 2020, 10 https://doi.org/10.3389/fcimb.2020.00388
    53. Kassiani Kytidou, Marta Artola, Herman S. Overkleeft, Johannes M. F. G. Aerts. Plant Glycosides and Glycosidases: A Treasure-Trove for Therapeutics. Frontiers in Plant Science 2020, 11 https://doi.org/10.3389/fpls.2020.00357
    54. Aadra P. Bhatt, Samuel J. Pellock, Kristen A. Biernat, William G. Walton, Bret D. Wallace, Benjamin C. Creekmore, Marine M. Letertre, Jonathan R. Swann, Ian D. Wilson, Jose R. Roques, David B. Darr, Sean T. Bailey, Stephanie A. Montgomery, Jeffrey M. Roach, M. Andrea Azcarate-Peril, R. Balfour Sartor, Raad Z. Gharaibeh, Scott J. Bultman, Matthew R. Redinbo. Targeted inhibition of gut bacterial β-glucuronidase activity enhances anticancer drug efficacy. Proceedings of the National Academy of Sciences 2020, 117 (13) , 7374-7381. https://doi.org/10.1073/pnas.1918095117
    55. Samantha M. Ervin, Siddharth Venkat Ramanan, Aadra P. Bhatt. Relationship Between the Gut Microbiome and Systemic Chemotherapy. Digestive Diseases and Sciences 2020, 65 (3) , 874-884. https://doi.org/10.1007/s10620-020-06119-3
    56. Alessandro Rizzo, Margherita Nannini, Marco Novelli, Angela Dalia Ricci, Valerio Di Scioscio, Maria Abbondanza Pantaleo. Dose reduction and discontinuation of standard-dose regorafenib associated with adverse drug events in cancer patients: a systematic review and meta-analysis. Therapeutic Advances in Medical Oncology 2020, 12 , 175883592093693. https://doi.org/10.1177/1758835920936932
    Download PDF
    Go to ACS Chemical Biology
    Get e-Alerts
    Get e-Alerts

    ACS Chemical Biology

    Cite this: ACS Chem. Biol. 2020, 15, 1, 217–225
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acschembio.9b00788
    Published November 27, 2019
    Copyright © 2019 American Chemical Society
    Request reuse permissions

    Article Views

    3596

    Altmetric

    -

    Citations

    56
    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.