文献类型：期刊文献

英文题名：Reprogramming ThDP Enzymes for Z-Alkenes: Overriding Thermodynamic Preference via Noncovalent Controls

作者：Li, Huangong[1,4];Yang, Tairan[1];Zhao, Yilong[1];Pan, Rui[1];Peng, Jinmin[1];Lai, Yinhong[1];Zhang, Jingyu[1];Liu, Xueting[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;[4]Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen 518055, Peoples R China

年份：2026

卷号：148

期号：29

起止页码：31120

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20263221266535);Scopus(收录号：2-s2.0-105046261661);WOS:【SCI-EXPANDED(收录号:WOS:001806732300001)】；

基金：We acknowledge the Open Access Platform for Large Instruments at East China University of Science and Technology for assistance with NMR spectroscopy. Our computational work was supported by Sci-Yue Smart Data Tech Co., Ltd. (Shanxi, China). This work was funded by the National Natural Science Foundation of China (32301231, 32121005, 32571667, 32327801), the Shanghai Municipal Science and Technology Major Project, the Shanghai Sci-Tech Inno Center for Infection & Immunity (Grant No. SSIII-2024A0301), the Shanghai Science and Technology Commission (24HC2820200, 24HC2810700), the International Cooperation and Exchange of the National Natural Science Foundation of China (No. W2412094), the Open Project Funding of the State Key Laboratory of Bioreactor Engineering, the 2023 Double World-Class Project-Key Program-Intelligent Biomanufacturing, and the 111 Project (B18022).

语种：英文

外文关键词：C (programming language) - Chelation - Chemical bonds - Complexation - Dehalogenation - Enzymes - Ligands - Plants (botany) - Scaffolds - Stereochemistry - Thermodynamics

摘要：Most conventional alkene synthesis reactions (e.g., elimination et al.) inherently favor the formation of thermodynamically more stable E-isomers, posing a long-standing challenge for direct access to Z-alkenes. Here, we report the reprogramming of a thiamine diphosphate (ThDP)-dependent enzyme to catalyze a formal dehalogenative elimination that overrides this intrinsic thermodynamic bias, enabling the direct and selective synthesis of Z-alpha,beta-unsaturated carboxylic acids. In contrast to classical approaches that rely on substrate control, directing groups, or complex ligand architectures, our strategy harnesses the enzyme's confined active site to achieve kinetic control exclusively via noncovalent interactions-representing a fundamentally distinct and more sustainable approach to stereochemical programming. This transformation diverts the enzyme from its native function in C-C bond formation by channeling the Breslow intermediate toward a homoenolate-mediated pathway, wherein specific noncovalent interactions stabilize the syn-periplanar geometry required for Z-selective dehalogenative elimination. Through rational active-site engineering, the stereochemical trajectory can be inverted to furnish the complementary E-isomer, enabling stereodivergent synthesis from a common scaffold. This work establishes a biocatalytic platform that addresses a critical gap in Z-alkene synthesis, expands the catalytic repertoire of ThDP-dependent enzymes, and provides a sustainable alternative to conventional methodologies.