Glycyl Radical Enzymes and the Human Gut
Glycyl radical enzymes (GREs) are abundant in the human gut microbiome. They use a post-translationally generated enzyme-bound glycyl radical species to carry out radical-based chemistry in anoxic environments. Our collaborator, Professor Emily Balskus (Harvard University), has pioneered a profiling strategy to discover novel GREs that are enriched in the human microbiome, and together, we carry out structure/function analyses of the resulting GREs. We recently solved a series of structures of choline trimethylamine-lyase (CutC), which produces trimethylamine (TMA), a microbial metabolite that is associated with nonalcoholic fatty acid liver disease, atherosclerosis, heart disease, diabetes and the metabolic disorder trimethylaminuria (fish malodor syndrome). We are currently working with the Balskus lab on inhibitor design in an attempt to provide the first medical remedy for fish malodor syndrome and to probe the importance of CutC activity to microbial communities and its impact on host health.
Bodea‡, S., Funk‡, M.A., Balskus*, E.P., and Drennan*, C.L. (2016) Molecular Basis of C–N Bond Cleavage by the Glycyl Radical Enzyme Choline Trimethylamine-Lyase, Cell Chem. Biol. 23, 1206-1216. PMCID: PMC5493019
Backman, L.R.F., Funk, M.A., Dawson, C.D., and Drennan*, C.L. (2017) New Tricks for the Glycyl Radical Enzyme Family, Crit. Rev. Biochem. Mol. Biol. 52, 674-695. PMCID: PMC5911432