Stereocontrol of Styrene Monooxygenases: Mechanistic Principles of (R)- and (S)-Selective Epoxidations and Their...

Numerous styrene monooxygenases (SMOs) have been identified and extensively applied in the asymmetric epoxidation of alkenes to prepare enantiopure epoxides, which are important intermediates in pharmaceuticals, agrochemicals, and fine chemicals. A current challenge is development of engineered SMOs capable of catalyzing a broad range of substrates with complementary enantioselectivity, thereby enabling the production of both (R)- and (S)-epoxides. Achieving this requires a deep understanding of the molecular basis underlying enantiocontrolling in SMO-catalyzed epoxidation. In this concept article, recent progress in elucidating the mechanisms of enantiocontrol by SMOs is summarized, with particular emphasis on the structural and mechanistic features that differentiate (R)- and (S)-selective SMOs. These insights not only expand fundamental knowledge of SMO catalysis but also provide a critical foundation for the rational design and protein engineering of highly efficient and versatile SMOs.