Biosynthesis of unique natural product scaffolds by Fe(II)/αKG-dependent oxygenases.

Fe(II)/αKG-dependent oxygenases are multifunctional oxidases responsible for the formation of unique natural product skeletons. Studies of these enzymes are important because the knowledge of their catalytic functions, enzyme structures, and reaction mechanisms can be used to create non-natural enzymes through mutation and synthesize non-natural compounds. In this review, I will introduce the research we have conducted on two fungal Fe(II)/αKG-dependent oxygenases, TlxI-J and TqaL. TlxI-J is the first Fe(II)/αKG-dependent oxygenase type enzyme heterodimer that catalyzes consecutive oxidation reactions, hydroxylation followed by retro-aldol or ketal formation, to form the complex skeletons of meroterpenoids. TqaL is the first naturally occurring aziridine synthase, and I will discuss the mechanism of its unique C-N bond formation in nonproteinogenic amino acid biosynthesis. This review will advance research on the discovery of new enzymes and the analysis of their functions by reviewing the structures and functions of these extraordinary Fe(II)/αKG-dependent oxygenases, and promote their use in the synthesis of new natural medicines.

© 2025. The Author(s).