Ferrous iron and α-ketoglutarate-dependent dioxygenases in the biosynthesis of microbial natural products

Apart from its vital role as the terminal electron acceptor in oxidative phosphorylation in nature, dioxygen also serves as a universal agent which diversifies natural products by oxidative transformations. Ferrous iron and α-ketoglutarate (αKG)-dependent dioxygenases (αKGDs) are versatile enzymes that use dioxygen as an oxidant to catalyse various reactions via CH bond activation, including hydroxylation, dealkylation, desaturation, epoxidation, epimerisation, halogenation, cyclisation, peroxide formation, and ring expansion/contraction reactions. This review updates the reported αKGDs that catalyse reactions related to microbial natural product biosynthesis in the past 10 years. We hope that the versatility of αKGDs shown here can serve as an inspiration for future engineering and catalyst design, which could provide alternative methods to meet the on-going demand for fine chemicals and pharmaceutics.