An Artificial Enzyme for Asymmetric Nitrocyclopropanation of α,β-Unsaturated Aldehydes - Design and Evolution

Angew Chem Int Ed Engl. 2024 Apr 10:e202401635. doi: 10.1002/anie.202401635. Online ahead of print.ABSTRACTThe 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 in high yield 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.PMID:38597773 | DOI:10.1002/anie.202401635

Source: Angewandte Chemie - April 10, 2024 Category: Chemistry Authors: Ming-Zhu Yu Ye Yuan Zhen-Jie Li Thittaya Kunthic He-Xiang Wang Chen Xu Zheng Xiang Source Type: research