In Vitro Reconstitution of a Bacterial Ergothioneine Sulfonate Catabolic Pathway

Naturally occurring l-ergothioneine is a ubiquitous histidine-derived sulfur metabolite produced by bacteria and fungi. Plants acquire ergothioneine from their soil environment, whereas animals accumulate it through dietary intake. It is widely believed that ergothioneine functions as a protective antioxidant to eradicate reactive oxygen and nitrogen species. Ergothioneine oxidation leads to the metabolite ergothioneine sulfonate. Using a “genomic enzymology” strategy, we have determined the chemical steps for the ergothioneine sulfonate catabolic pathway, which involves a previously unknown reductive desulfonation reaction catalyzed by members of ornithine cyclodeaminase superfamily. In vitro reconstitution of the full pathway was demonstrated using the cloned and purified pathway enzymes fromAgrobacterium radiobacter K84. Through the identification of pathway gene homologues, the biological range of the ergothioneine sulfonate pathway was found to include α-,γ-proteobacterial, and actinobacterial species.