A Widespread, Diiron-dependent Diterpenoid Hydroxylase
This communication describes the discovery of a family of monooxygenases that selectively hydroxylate abundant abietane diterpenoids. Previous studies on abietic acid metabolism had implicated an unknown C(5) hydroxylase and herein we determine that this role is filled by DitZ. Structural and sequence analyses indicate that DitZ represents a new member of the Amidohydrolase-related Dinuclear Oxygenase (ADO) superfamily. Kinetic studies on multiple DitZ enzymes reflect highly efficient and selective C(5) hydroxylation of a range of diterpenoids using only O2 and a sacrificial reductant (sodium ascorbate) as co-reagents. These enzymatic reactions are promoted by a diiron cofactor that has access to multiple observable redox states.