Enantiocomplementary Epoxidation Reactions Catalyzed by an Engineered Cofactor‐Independent Non‐Natural Peroxygenase

• Published in: Angewandte Chemie International Edition
• Main Authors: Xu, Guangcai, Crotti, Michele, Thangavelu, Saravan, Kataja, Kim, Poelarends, Gerrit J.
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2020
• Subjects: MICHAEL-TYPE ADDITIONS; PEROXIDE-DRIVEN HYDROXYLATION; ANTARCTICA LIPASE B; 4-OXALOCROTONATE TAUTOMERASE; ASYMMETRIC EPOXIDATION; CHLOROPEROXIDASE; ACETALDEHYDE; OXIDATIONS; ALDEHYDES; ENZYMES; Antarc*; Antarctica
• Online Access: https://hdl.handle.net/11370/3f4521bb-acfc-41f7-ad68-ae9bff4d983b; https://research.rug.nl/en/publications/3f4521bb-acfc-41f7-ad68-ae9bff4d983b; https://doi.org/10.1002/anie.202001373; https://pure.rug.nl/ws/files/131633242/anie.202001373.pdf

Peroxygenases are heme-dependent enzymes that use peroxide-borne oxygen to catalyze a wide range of oxyfunctionalization reactions. Herein, we report the engineering of an unusual cofactor-independent peroxygenase based on a promiscuous tautomerase that accepts different hydroperoxides (t-BuOOH and H 2 O 2 ) to accomplish enantiocomplementary epoxidations of various α,β-unsaturated aldehydes (citral and substituted cinnamaldehydes), providing access to both enantiomers of the corresponding α,β-epoxy-aldehydes. High conversions (up to 98 %), high enantioselectivity (up to 98 % ee), and good product yields (50–80 %) were achieved. The reactions likely proceed via a reactive enzyme-bound iminium ion intermediate, allowing tweaking of the enzyme's activity and selectivity by protein engineering. Our results underscore the potential of catalytic promiscuity for the engineering of new cofactor-independent oxidative enzymes.