Discovery and characterization of a prevalent human gut bacterial enzyme sufficient for the inactivation of a family of plant toxins.

TitleDiscovery and characterization of a prevalent human gut bacterial enzyme sufficient for the inactivation of a family of plant toxins.
Publication TypeJournal Article
Year of Publication2018
AuthorsKoppel, N, Bisanz, JE, Pandelia, M-E, Turnbaugh, PJ, Balskus, EP
JournalElife
Volume7
Date Published2018 May 15
ISSN2050-084X
Abstract

Although the human gut microbiome plays a prominent role in xenobiotic transformation, most of the genes and enzymes responsible for this metabolism are unknown. Recently, we linked the two-gene 'cardiac glycoside reductase' () operon encoded by the gut Actinobacterium to inactivation of the cardiac medication and plant natural product digoxin. Here, we compared the genomes of 25 strains and close relatives, revealing an expanded 8-gene -associated gene cluster present in all digoxin metabolizers and absent in non-metabolizers. Using heterologous expression and in vitro biochemical characterization, we discovered that a single flavin- and [4Fe-4S] cluster-dependent reductase, Cgr2, is sufficient for digoxin inactivation. Unexpectedly, Cgr2 displayed strict specificity for digoxin and other cardenolides. Quantification of in gut microbiomes revealed that this gene is widespread and conserved in the human population. Together, these results demonstrate that human-associated gut bacteria maintain specialized enzymes that protect against ingested plant toxins.

DOI10.7554/eLife.33953
Alternate JournalElife
PubMed ID29761785
Grant ListGraduate Science and Engineering Fellowship / / Smith family /
Graduate student fellowship, DGE1144152 / / National Science Foundation /
Training grant, GM095450-01 / / National Institutes of Health /
Postdoctoral fellowship / / Natural Sciences and Engineering Research Council of Canada /
GM111978 / / National Institutes of Health /
R01HL122593 / / National Institutes of Health /
SSP-2016-1352; EB:12-SSP-243 / / Searle Scholars Program /
DRR-42-16 / / Damon Runyon Cancer Research Foundation / United States
Program for Breakthrough Biomedical Research / / University of California, San Francisco /
2013-39267 / / David and Lucile Packard Foundation /
27-14 / / George W. Merck Fellowship /
OPP1158186 / / Bill and Melinda Gates Foundation /
12-SSP-243 / / Searle Scholars Program /