Yokoyama Lab Found the Novel Reactivity of an Fe-dependent Oxidase in Antifungal Biosynthesis

Chemical structures of O-H activation

In a recently published study available in the Journal of the American Chemical Society, the Yokoyama lab characterized the mechanism of oxidative C-C bond cleavage reaction catalyzed by Fe and 2-oxoglutarate (2-OG)-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. Most significantly, they found 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 the very first example of radical initiation by O-H activation in the huge superfamily of Fe/2-OG enzymes. Read more on the Yokoyama Lab's recent work here.