In this study, we characterized the mechanism of oxidative C-C bond cleavage reaction catalyzed by Fe and 2-oxoglutarate-dependent oxidase, PolD. This enzyme diverges the biosynthetic pathways between C6 and C7-sugar nucleoside antifungals, and therefore, its mechanistic and structural understanding is important for the future genome-mining discovery of novel antifungals. The results suggested that the reaction is initiated by an unexpected O-H bond homolysis. Aliphatic O-H bonds have very high bond dissociation energy (~105 kcal/mol), and this report represents, to our knowledge, the very first example of radical initiation by O-H activation in Fe and 2-OG enzymes.
Department of Biochemistry, Duke University School of Medicine
