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 in vitro reconstruction using heterologously produced enzymes derived from
the human gut bacterium Blautia producta ATCC 27340. This catabolic activity enables B. producta ATCC 27340 to use ergothioneine as an alternative electron acceptor
source. Homologues of the pathway enzymes are shown to be present
not only in human gut bacteria but also in many environmental bacteria,
suggesting the wide distribution of this catabolic strategy. In relation
to the sulfur-containing metabolite, this discovery provides significant
insight into biogeochemical sulfur cycling in diverse anoxic habitats
beyond the human gut and, moreover, the design of new approaches for
controlling intestinal hydrogen sulfide (H2S) production.