文献类型：期刊文献

英文题名：Enzyme-Catalyzed Intramolecular C-C Coupling Transformation of Nitriles

作者：Zhu, Chaonan[1];Wu, Dongqi[1];Lai, Yinhong[1];Li, Huangong[1];Pan, Rui[1];Zou, Keke[1];Chen, Qi[1];Zhu, Guoliang[1];Zhang, Lixin[1];Chi, Yonggui Robin[2,3];Xie, Yongtao[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Nanyang Technol Univ, Sch Chem Chem Engn & Biotechnol, Singapore 637371, Singapore;[3]Guizhou Univ, Natl Key Lab Green Pesticide, Key Lab Green Pesticide & Agr Bioengn, Minist Educ, Guiyang 550025, Peoples R China

年份：2026

卷号：148

期号：9

起止页码：10257

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20261120259738);WOS:【SCI-EXPANDED(收录号:WOS:001703243700001)】；

基金：We acknowledge the National Natural Science Foundation of China (32301231), the Shanghai Sci-Tech Inno Center for Infection & Immunity (Grant No. SSIII-2024A0301), the Shanghai Science and Technology Commission (24HC2820200, 24HC2810700), Shanghai Municipal Science and Technology Major Project, National Key Research and Development Program of China (2020YFA0907200, 2020YFA0907800, 2022YFC2303100 and 2022YFC2303104), the Open Project Funding of the State Key Laboratory of Bioreactor Engineering, and the 111 Project (B18022).

语种：英文

外文关键词：Addition reactions - Catalysis - Chemical bonds - Hydrolysis - In situ processing - Synthesis (chemical)

摘要：Nitrile C-C coupling transformation, currently absent from existing biocatalytic toolbox, is a pivotal objective in enzyme catalysis. Herein, we engineered a ThDP-dependent enzyme to achieve nitrile C-C coupling with in situ-generated acyl anion equivalent, providing a valuable synthetic complement to current enzymatic transformations. This reaction also constitutes the first ThDP-dependent enzymatic addition of aldehyde group to an inert triple bond. Under mildly acidic aqueous conditions, this biocatalytic reaction achieves effective hydrolysis of readily isomerizable imine intermediates. Such a hydrolysis process poses formidable challenges to organic solvent-reliant chemical reactions and has been scarcely explored. In addition, this reaction constitutes an enzyme-catalyzed, oxidant-free strategy for the efficient synthesis of valuable 3-hydroxychromones-key intermediates for accessing flavonol natural products and functional molecules. Related mechanistic studies and preliminary kinetic resolution experiments were also conducted. Our study will encourage further development of biocatalytic systems for nitrile C-C coupling transformations, particularly those challenging to chemical methods.