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An Artificial Enzyme for Asymmetric Nitrocyclopropanation of α,β-Unsaturated Aldehydes-Design and Evolution
Ming-Zhu Yu1, Ye Yuan1, Zhen-Jie Li2
1State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Genomics, AI for Science (AI4S) Preferred Program, School of Chemical Biology and Biotechnology Peking University Shenzhen Graduate School, University Town of Shenzhen, Nanshan District, 518055, Shenzhen, P. R. China.
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.
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