Metatranscriptomics-guided discovery and characterization of a polyphenol-metabolizing gut microbial enzyme

Minwoo Bae; Chi Le; Raaj S Mehta; Xueyang Dong; Lindsey M Pieper; Lorenzo Ramirez; Margaret Alexander; Sina Kiamehr; Peter J Turnbaugh; Curtis Huttenhower; Andrew T Chan; Emily P Balskus

doi:10.1016/j.chom.2024.10.002

Metatranscriptomics-guided discovery and characterization of a polyphenol-metabolizing gut microbial enzyme

Cell Host Microbe. 2024 Nov 13;32(11):1887-1896.e8. doi: 10.1016/j.chom.2024.10.002. Epub 2024 Oct 28.

Authors

Affiliations

¹ Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
² Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
³ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
⁴ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Chan Zuckerberg Biohub-San Francisco, San Francisco, CA 94158, USA.
⁵ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Harvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA.
⁶ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
⁷ Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address: [email protected].

PMID: 39471822
DOI: 10.1016/j.chom.2024.10.002

Abstract

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.

Keywords: catechol dehydroxylase; diet; gut microbe; inflammation; metatranscriptomics; polyphenol.

MeSH terms

Actinobacteria / enzymology
Actinobacteria / genetics
Bacterial Proteins / genetics
Bacterial Proteins / metabolism
Gastrointestinal Microbiome*
Gene Expression Profiling
Humans
Polyphenols* / metabolism

Substances

Polyphenols
Bacterial Proteins