An Artificial Enzyme for Asymmetric Nitrocyclopropanation of α,β‐Unsaturated Aldehydes—Design and Evolution
Mingzhu Yu, Ye Yuan, Zhenjie Li, Thittaya Kunthic, He‐Xiang Wang, Chen Xu, Zheng Xiang
Abstract
The introduction of an abiological catalytic group into the binding pocket of a protein host allows for the expansion of enzyme chemistries. Here, we report the generation of an artificial enzyme by genetic encoding of a non-canonical amino acid that contains a secondary amine side chain. The non-canonical amino acid and the binding pocket function synergistically to catalyze the asymmetric nitrocyclopropanation of α,β-unsaturated aldehydes by the iminium activation mechanism. The designer enzyme was evolved to an optimal variant that catalyzes the reaction at high conversions with high diastereo- and enantioselectivity. This work demonstrates the application of genetic code expansion in enzyme design and expands the scope of enzyme-catalyzed abiological reactions.