Enabling Highly (R)-Enantioselective Epoxidation of Styrene by Engineering Unique Non-Natural P450 Peroxygenases

02 November 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Unlike the excellent (S)-enantioselective epoxidation of styrene performed by natural styrene monooxygenase (ee >99%), the (R)-enantioselective epoxidation of styrene has not yet achieved a comparable efficiency using natural or engineered oxidative enzymes. This report describes the H2O2-dependent (R)-enantioselective epoxidation of unfunctionalized styrene and its derivatives by site-mutated variants of a unique non-natural P450BM3 peroxygenase, working in tandem with a dual-functional small molecule (DFSM). The observed (R)-enantiomeric excess of styrene epoxidation is up to ~99%, which is unprecedented relative to natural or engineered oxidative enzymes. The catalytic turnover number is up to ~4500 (with ~98% ee), representing the best activity of a P450 peroxygenase towards styrene epoxidation, to date. This study indicates that the synergistic use of protein engineering and an exogenous DFSM constitutes an efficient strategy to control enantioselectivity of styrene epoxidation, thus substantially expanding the chemical scope of P450 enzyme functions as useful bio-oxidative catalysts.


enantioselective epoxidation
peroxygenase activity
protein engineering


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