@article{5e19622a53304cb99b164e833d7dabc4,
title = "A Metabolic Pathway for Activation of Dietary Glucosinolates by a Human Gut Symbiont",
abstract = "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.",
keywords = "Bacteroides thetaiotaomicron, glucosinolate, gut microbe, isothiocyanate, myrosinase, phytonutrient",
author = "Liou, {Catherine S.} and Sirk, {Shannon J.} and Diaz, {Camil A.C.} and Klein, {Andrew P.} and Fischer, {Curt R.} and Higginbottom, {Steven K.} and Amir Erez and Donia, {Mohamed S.} and Sonnenburg, {Justin L.} and Sattely, {Elizabeth S.}",
note = "Funding Information: This work was supported by HHMI and Simons Foundation grant 55108565 and NIH DP2AT00832101 (to E.S.S.); Stanford Bio-X Bowes (to C.S.L.); and ChEM-H seed grant funding (to J.L.S. and E.S.S.). We thank M. Fischbach, E. Carlson, and M. Voges (Stanford) for comments on the manuscript and K. Smith, R. de la Pena, and other members of the Sattely lab for helpful discussions. We thank K. Ng, D. Dodd, and E. Shepherd (Stanford) for assistance with and advice regarding gnotobiotic mouse studies and W. Whitaker (Stanford) for providing the Bacteroides phage promoter sequence. We thank A. Wawro (Stanford) for assistance with methods for creatinine measurements. We thank M. Wang (Stanford) for providing Bacteroides strains. We thank C. Miller, S. Hull, and S. Lensch (Stanford) for their efforts regarding in vitro biochemical characterization. We thank S. Mazmanian (California Institute of Technology) for providing plasmid pFD340. We thank the Stanford High-Throughput Bioscience Center for technical assistance with the Bt mutant screen. C.S.L. S.J.S. C.A.C.D. A.P.K. C.R.F. J.L.S. and E.S.S. designed the experiments and analyzed the data. C.S.L. S.J.S. C.A.C.D. A.P.K. C.R.F. and S.K.H. performed the experiments. S.J.S. and C.S.L. wrote the paper with edits from E.S.S. C.A.C.D. A.P.K. and C.R.F. The authors declare no competing interests. Funding Information: This work was supported by HHMI and Simons Foundation grant 55108565 and NIH DP2AT00832101 (to E.S.S.); Stanford Bio-X Bowes (to C.S.L.); and ChEM-H seed grant funding (to J.L.S. and E.S.S.). We thank M. Fischbach, E. Carlson, and M. Voges (Stanford) for comments on the manuscript and K. Smith, R. de la Pena, and other members of the Sattely lab for helpful discussions. We thank K. Ng, D. Dodd, and E. Shepherd (Stanford) for assistance with and advice regarding gnotobiotic mouse studies and W. Whitaker (Stanford) for providing the Bacteroides phage promoter sequence. We thank A. Wawro (Stanford) for assistance with methods for creatinine measurements. We thank M. Wang (Stanford) for providing Bacteroides strains. We thank C. Miller, S. Hull, and S. Lensch (Stanford) for their efforts regarding in vitro biochemical characterization. We thank S. Mazmanian (California Institute of Technology) for providing plasmid pFD340. We thank the Stanford High-Throughput Bioscience Center for technical assistance with the Bt mutant screen. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = feb,
day = "20",
doi = "10.1016/j.cell.2020.01.023",
language = "English (US)",
volume = "180",
pages = "717--728.e19",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}