Discovery, Characterization and Synthetic Application of a Promiscuous Nonheme Iron Biocatalyst with Dual Hydroxylase/Desaturase Activity

Alpha‐ketoglutarate‐dependent dioxygenases (αKGDs) have recently emerged as useful biocatalysts for C−H oxidation and functionalization. In this work, we characterized a new αKGD from aculene biosynthesis, AneA, which displays broad promiscuity toward a number of substrates with different ring systems. Unexpectedly, AneA was found to be capable of both desaturation and hydroxylation and require an amino ester motif on its substrate for productive catalysis. Insights gathered from the functional characterization and substrate‐activity profiling of AneA enabled the development of a chemoenzymatic strategy toward several complex sesquiterpenoids.