Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria
Name
nihms-1020956.pdf
Description
Accepted version
Size
767.15 KB
Format
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Checksum (MD5)
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Author(s)
Orman, Marina
Bodea, Smaranda
Funk, Michael A.
Campo, Ana Martínez-del
Bollenbach, Maud
Drennan, Catherine L
Balskus, Emily P.
Date Issued
December 2018
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Orman, Marina et al. "Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria." Journal of the American Chemical Society 141, 1 (December 2018): 33–37. © 2018 American Chemical Society
Version
Author's final manuscript
Abstract
The anaerobic gut microbial pathway that converts choline into trimethylamine (TMA) is broadly linked to human disease. Here, we describe the discovery that betaine aldehyde inhibits TMA production from choline by human gut bacterial isolates and a complex gut community. In vitro assays and a crystal structure suggest betaine aldehyde targets the gut microbial enzyme choline TMA-lyase (CutC). In our system, we do not observe activity for the previously reported CutC inhibitor 3,3-dimethylbutanol (DMB). The workflow we establish for identifying and characterizing betaine aldehyde provides a framework for developing additional inhibitors of gut microbial choline metabolism, including therapeutic candidates.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Biology
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1021/jacs.8b04883
