Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria
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 crysta...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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American Chemical Society (ACS)
2020
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| Online Access: | https://hdl.handle.net/1721.1/128651 |
| _version_ | 1811087981821296640 |
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| author | Orman, Marina Bodea, Smaranda Funk, Michael A. Campo, Ana Martínez-del Bollenbach, Maud Drennan, Catherine L Balskus, Emily P. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Orman, Marina Bodea, Smaranda Funk, Michael A. Campo, Ana Martínez-del Bollenbach, Maud Drennan, Catherine L Balskus, Emily P. |
| author_sort | Orman, Marina |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:54:38Z |
| format | Article |
| id | mit-1721.1/128651 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:54:38Z |
| publishDate | 2020 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1286512022-09-28T17:02:22Z Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria Orman, Marina Bodea, Smaranda Funk, Michael A. Campo, Ana Martínez-del Bollenbach, Maud Drennan, Catherine L Balskus, Emily P. Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Department of Biology 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. 2020-11-24T23:24:34Z 2020-11-24T23:24:34Z 2018-12 2018-05 2020-09-18T18:26:52Z Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 https://hdl.handle.net/1721.1/128651 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 en http://dx.doi.org/10.1021/jacs.8b04883 Journal of the American Chemical Society 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. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Orman, Marina Bodea, Smaranda Funk, Michael A. Campo, Ana Martínez-del Bollenbach, Maud Drennan, Catherine L Balskus, Emily P. Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria |
| title | Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria |
| title_full | Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria |
| title_fullStr | Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria |
| title_full_unstemmed | Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria |
| title_short | Structure-Guided Identification of a Small Molecule That Inhibits Anaerobic Choline Metabolism by Human Gut Bacteria |
| title_sort | structure guided identification of a small molecule that inhibits anaerobic choline metabolism by human gut bacteria |
| url | https://hdl.handle.net/1721.1/128651 |
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