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’ (cgr) operon encoded by the gut Actinobacterium Eggerthella lenta to inactivation of the cardiac medication and plant natural product digoxin. Here, we compared the genomes of 25 E. lenta strains and close relatives, revealing an expanded 8-gene cgr-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 cgr2 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.
Discovery and characterization of a prevalent human gut bacterial enzyme sufficient for the inactivation of a family of plant toxins
N. Koppel,J. Bisanz,M. Pandelia,P. Turnbaugh,E. Balskus
Published 2018 in eLife
ABSTRACT
PUBLICATION RECORD
- Publication year
2018
- Venue
eLife
- Publication date
2018-03-20
- Fields of study
Biology, Medicine, Environmental Science
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
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