Discovery of a Gut Bacterial Pathway for Ergothioneine Catabolism

Ergothioneine is a diet-derived micronutrient for humans. However, enzymes involved in the catabolism of ergothioneine in human gut bacteria have not yet been identified. Herein, we characterize a sulfidogenic pathway for gut bacterial catabolism of this micronutrient, which involves an unprecedented reductive desulfurization reaction catalyzed by members of the xanthine oxidoreductase family (XOR), a class of molybdenum-containing flavoproteins. Notably, this is the first C-S bond cleavage reaction known to be catalyzed by XORs. Evidence for operation of this pathway was gained through