Harnessing Fe(II)/α-ketoglutarate-dependent oxygenases for structural diversification of fungal meroterpenoids.

Fungal meroterpenoids are structurally diverse natural products with important biological activities. During their biosynthesis, α-ketoglutarate-dependent oxygenases (αKG-DOs) catalyze a wide range of chemically challenging transformation reactions, including desaturation, epoxidation, oxidative rearrangement, and endoperoxide formation, by selective C-H bond activation, to produce molecules with more complex and divergent structures. Investigations on the structure-function relationships of αKG-DO enzymes have revealed the intimate molecular bases of their catalytic versatility and reaction mechanisms. Notably, the catalytic repertoire of αKG-DOs is further expanded by only subtle changes in their active site and lid-like loop-region architectures. Owing to their remarkable biocatalytic potential, αKG-DOs are ideal candidates for future chemoenzymatic synthesis and enzyme engineering for the generation of terpenoids with diverse structures and biological activities.