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The crystal structure of styrene monooxygenase StyA from Streptomyces vilmorinianum
Structural highlights
Publication Abstract from PubMedGroup E flavoprotein monooxygenases (GEMs) are well-known for catalyzing enantioselective epoxidation reactions. However, engineering their enantioselectivity remains a significant challenge, largely due to a limited understanding of the underlying mechanisms. Among these enzymes, (R)-selective styrene monooxygenases ((R)-SMOs) stand out due to their unusual enantio-switch behavior when catalyzing the reactions of p-substituted styrenes. This unique property provides an exceptional opportunity to investigate the enantiocontrol mechanisms within GEMs. In this study, we resolved the first crystal structure of an (R)-SMO, SeStyA, derived from Streptomyces. By integrating this structural information with molecular docking and molecular dynamics (MD) simulations, we identified four key residues critical to enantiodivergency: two distal residues (S178 and A219) and two proximal residues (A59 and A312). Strikingly, a "tug-of-war" mechanism was revealed through saturation mutagenesis, wherein the side-chain sizes of proximal and distal residues exerted opposing influences on enantioselectivity at the C=C bond. Leveraging this mechanistic insight, we successfully engineered SMOs with excellent (R)- or (S)-enantioselectivity. Structural and Mechanistic Insight into the Enantioselectivity of (R)-Selective Styrene Monooxygenases: A Tug-of-War between Proximal and Distal Residues.,Li ZP, Wang L, Liu Y, Pei XQ, Fatmi MQ, Shen Z, Zhao J, Lin H, Zhou J, Wu ZL Angew Chem Int Ed Engl. 2025 Feb 14:e202423117. doi: 10.1002/anie.202423117. PMID:39950369[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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