Engineered P450 Atom-Transfer Radical Cyclases are Bifunctional Biocatalysts: Reaction Mechanism and Origin of Enantioselectivity.

ABSTRACT: New-to-nature radical biocatalysis has recently emerged as a powerful strategy to tame fleeting open-shell intermediates for stereoselective transformations. In 2021, we introduced a novel metalloredox biocatalysis strategy that leverages the innate redox properties of the heme cofactor of P450 enzymes, furnishing new-to-nature atom-transfer radical cyclases (ATRCases) with excellent activity and stereoselectivity. Herein, we report a combined computational and experimental study to shed light on the mechanism and origins of enantioselectivity for this system. Molecular dynamics and quantum mechanics/molecular mechanics (QM/MM) calculations revealed an unexpected role of the key beneficial mutation I263Q. The glutamine residue serves as an essential hydrogen bond donor that engages with th

SUBMITTER: Fu Y 

PROVIDER: S-EPMC9339536 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature