Metatranscriptomics-guided discovery and characterization of a polyphenol-metabolizing gut microbial enzyme
Gut microbial catechol dehydroxylases are a largely uncharacterized family of metalloenzymes that potentially impact human health by metabolizing dietary polyphenols. Here, we use metatranscriptomics (MTX) to identify highly transcribed catechol-dehydroxylase-encoding genes in human gut microbiomes. We discover a prevalent, previously uncharacterized catechol dehydroxylase (Gp Hcdh) from Gordonibacter pamelaeae that dehydroxylates hydrocaffeic acid (HCA), an anti-inflammatory gut microbial metabolite derived from plant-based foods. Further analyses suggest that the activity of Gp Hcdh may reduce anti-inflammatory benefits of polyphenol-rich foods. Together, these results show the utility of combining MTX analysis and biochemical characterization for gut microbial enzyme discovery and reveal a potential link between host inflammation and a specific polyphenol-metabolizing gut microbial enzyme.
Authors
- Curtis Huttenhower (ORCID: https://orcid.org/0000-0002-1110-0096)
- Margaret Alexander (ORCID: https://orcid.org/0000-0003-2972-7521)
- Raaj S. Mehta
- Lindsey M. Pieper (ORCID: https://orcid.org/0000-0003-3022-5721)
- Xueyang Dong (ORCID: https://orcid.org/0000-0003-2186-1726)
- Minwoo Bae (ORCID: https://orcid.org/0000-0002-0313-5520)
- Sina Kiamehr (ORCID: https://orcid.org/0000-0002-4917-9393)
- Andrew T. Chan (ORCID: https://orcid.org/0000-0001-7284-6767)
- Emily P. Balskus (ORCID: https://orcid.org/0000-0001-5985-5714)
- Peter J. Turnbaugh (ORCID: https://orcid.org/0000-0002-0888-2875)
- A. Lorenzo (ORCID: https://orcid.org/0000-0003-1019-2635)
- Chi Hieu Le (ORCID: https://orcid.org/0000-0002-5168-2297)
Institutions
- Broad Institute (US)
- Harvard University (US)
- University of California, San Francisco (US)
- Harvard University Press (US)
- Massachusetts General Hospital (US)
- Chan Zuckerberg Initiative (United States) (US)
Publication Details
- Journal
- Cell Host & Microbe
- Published
- 2024-10-28
- DOI
- https://doi.org/10.1016/j.chom.2024.10.002
- Citations
- 24
- Primary Topic
- Probiotics and Fermented Foods
- Type
- article
- Field-Weighted Citation Impact
- 8.36
Funders
- National Science Foundation
- National Institutes of Health
- Division of Chemistry