biostudies-literatureLiou CSSimons FoundationStanford Bio-XNCCIH NIH HHSNIDDK NIH HHSHoward Hughes Medical InstituteNational Institutes of HealthNIGMS NIH HHS717-728.e19https://www.ebi.ac.uk/biostudies/studies/S-EPMC7515767biostudies-literatureUnknown180(4)Consumption of glucosinolates, pro-drug-like metabolites abundant in Brassica vegetables, has been associated with decreased risk of certain cancers. Gut microbiota have the ability to metabolize glucosinolates, generating chemopreventive isothiocyanates. Here, we identify a genetic and biochemical basis for activation of glucosinolates to isothiocyanates by Bacteroides thetaiotaomicron, a prominent gut commensal species. Using a genome-wide transposon insertion screen, we identified an operon required for glucosinolate metabolism in B. thetaiotaomicron. Expression of BT2159-BT2156 in a non-metabolizing relative, Bacteroides fragilis, resulted in gain of glucosinolate metabolism. We show that isothiocyanate formation requires the action of BT2158 and either BT2156 or BT2157 in vitro. Monocolonization of mice with mutant BtΔ2157 showed reduced isothiocyanate production in the gastrointestinal tract. These data provide insight into the mechanisms by which a common gut bacterium processes an important dietary nutrient.CellA Metabolic Pathway for Activation of Dietary Glucosinolates by a Human Gut Symbiont.PMC7515767R01 DK085025DP2AT00832101DP2 AT008321T32 GM12000755108565Sonnenburg JLSirk SJSattely ESLiou CSHigginbottom SKErez ADonia MSDiaz CACKlein APFischer CRfalseA Metabolic Pathway for Activation of Dietary Glucosinolates by a Human Gut Symbiont.Consumption of glucosinolates, pro-drug-like metabolites abundant in Brassica vegetables, has been associated with decreased risk of certain cancers. Gut microbiota have the ability to metabolize glucosinolates, generating chemopreventive isothiocyanates. Here, we identify a genetic and biochemical basis for activation of glucosinolates to isothiocyanates by Bacteroides thetaiotaomicron, a prominent gut commensal species. Using a genome-wide transposon insertion screen, we identified an operon required for glucosinolate metabolism in B. thetaiotaomicron. Expression of BT2159-BT2156 in a non-metabolizing relative, Bacteroides fragilis, resulted in gain of glucosinolate metabolism. We show that isothiocyanate formation requires the action of BT2158 and either BT2156 or BT2157 in vitro. Monocolonization of mice with mutant BtΔ2157 showed reduced isothiocyanate production in the gastrointestinal tract. These data provide insight into the mechanisms by which a common gut bacterium processes an important dietary nutrient.2020-01-01T00:00:00Z2020 Feb2024-11-14T14:24:59.528Z2021-02-23T08:05:13ZS-EPMC75157673208434110.1016/j.cell.2020.01.023