Revealing the Monooxygenase Mechanism for Selective Ring Cleavage of Anthraquinone by BTG13 through Multiscale Simulations

BTG13, a non‐heme iron‐dependent enzyme with a distinctive coordination environment of four histidines and a carboxylated lysine, has been found to catalyze the cleavage of the C4a−C10 bond in anthraquinone. Contrary to typical dioxygenase mechanisms, our quantum mechanical/molecular mechanical (QM/MM) calculations reveal that BTG13 functions more like a monooxygenase. It selectively inserts an oxygen atom into the C10−C4a bond, creating a lactone species that subsequently hydrolyzes, leading to the formation of a ring‐opened product. This discovery highlights the unique catalytic properties of BTG13 and expands our understanding of non‐heme iron enzyme mechanisms.