Figure 1.

IslA-mediated anaerobic metabolism of organosulfonates by intestinal bacteria releases the disease-associated metabolite hydrogen sulfide (H₂S)

(A) Deamination of taurine by human gut microbes yields isethionate (Ise), which is cleaved and reduced to H₂S in microbial respiration.

(B) The activating enzyme for IslA, IslB, installs a glycyl radical on a particular glycine residue of IslA using radical SAM chemistry, i.e., the formation of a 5′-deoxyadenosyl radical (Ado⋅) species from the reductive cleavage of S-adenosylmethionine (AdoMet) using an one electron reduced [4Fe-4S] cluster. The glycyl radical (Gly⋅) transiently forms the catalytically essential thiyl radical species (Cys⋅).

(C) Proposed reaction scheme for IslA. Radical species are shown in red.