Project description:Urolithin A is a polyphenol derived from the multi-step metabolism of dietary ellagitannins by the human gut microbiota which can affect host health. Most, but not all, individuals harbor a microbiota capable of urolithin A production; however, the enzymes that dehydroxylate its dietary precursor, urolithin C, are unknown. Here, we used a combination of transcriptomics and proteomics to reveal a urolithin C dehydroxylase (ucd) operon that dehydroxylates 9-hydroxy urolithin compounds in Enterocloster spp. Using comparative genomics, we identified Lachnoclostridium pacaense as a novel urolithin C metabolizer. Biochemical characterization and structure predictions of proteins in the Ucd complex demonstrated that dehydroxylation was both NADH- and molybdopterin-dependent and used urolithin C as a terminal electron acceptor. A meta-analysis publicly available metagenomic data revealed that both bacteria and ucd operon genes are widely distributed in gut metagenomes and likely comprise keystone species in the metabolism of urolithins by the human gut microbiota.
