Bienzyme-Catalytic and Dioxygenation-Mediated Anthraquinone Ring Opening

The C-10–C-4a bond cleavage of anthraquinone is believed to be a crucial step in fungal seco-anthraquinone biosynthesis and has long been proposed as a classic Baeyer–Villiger oxidation. Nonetheless, genetic, enzymatic, and chemical information on ring opening remains elusive. Here, a revised questin ring-opening mechanism was elucidated by in vivo gene disruption, in vitro enzymatic analysis, and 18 O chasing experiments. It has been confirmed that the reductase GedF is responsible for the reduction of the keto group at C-10 in questin to a hydroxyl group with the aid of NADPH. The C-10–C-4a bond of the resultant questin hydroquinone is subsequently cleaved by the atypical cofactor-free dioxygenase GedK, giving rise to desmethylsulochrin. This proposed bienzyme-catalytic and dioxygenation-mediated anthraquinone ring-opening reaction shows universality.