Discovery of Noncanonical Iron and 2-Oxoglutarate Dependent Enzymes Involved in C-C and C-N Bond Formation in Biosynthetic Pathways.

Iron and 2-oxoglutarate dependent (Fe/2OG) enzymes utilize an Fe=O species to catalyze the functionalization of otherwise chemically inert C-H bonds. In addition to the more familiar canonical reactions of hydroxylation and chlorination, they also catalyze several other types of reactions that contribute to the diversity and complexity of natural products. In the past decade, several new Fe/2OG enzymes that catalyze C-C and C-N bond formation have been reported in the biosynthesis of structurally complex natural products. Compared with hydroxylation and chlorination, the catalytic cycles of these Fe/2OG enzymes involve distinct mechanistic features to enable noncanonical reaction outcomes. This Review summarizes recent discoveries of Fe/2OG enzymes involved in C-C and C-N bond formation with a focus on reaction mechanisms and their roles in natural product biosynthesis.