Electricity-driven enzymatic dynamic kinetic oxidation

• 成果类型: Article
• 署名作者: Zhao, Beibei; Xu, Yuanyuan; Zhu, Qin; Liu, Aokun; Peng, Xichao; Zhang, Tianying; Yu, Lu; Zhang, Yan; Huang, Xiaoqiang
• 署名单位: Nanjing University; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; Hefei Institutes of Physical Science, CAS
• 刊物名称: Nature
• ISSN/ISSBN: 0028-1250
• DOI: 10.1038/s41586-025-09178-6
• 发表日期: 2025-07-17
• 关键词: asymmetric-synthesis; strategies

摘要

Electrochemistry is undergoing a resurgence in synthetic chemistry and has compelling advantages1. Repurposing natural enzymes through synthetic chemical strategies holds promise for exploring new chemical space2, 3, 4, 5-6. Elegant strategies, including directed evolution7, 8, 9-10, artificial enzymes11 and photoenzymatic catalysis12,13, have demonstrated their capacities for expanding the applications of enzymes in both academia and industry. However, the integration of electrochemistry with enzymes has primarily been limited to replicating previously established enzyme functions14, 15-16. Key challenges in achieving new enzyme reactivity with electricity include compatibility issues and difficulties in heterogeneous electron transfer. Here we report the reshaping of thiamine-dependent enzymes with ferrocene-mediated electrocatalysis to unlock an unnatural dynamic kinetic oxidation of alpha-branched aldehydes. This robust electroenzymatic approach yields various bioactive (S)-profens with up to 99% enantiomeric excess; it is applicable with whole cells overexpressing the enzyme and using down to 0.05 mol% enzyme loadings. Mechanistic investigations show multiple functions of the electroenzyme in precise substrate discrimination, accelerating racemization and facilitating kinetically matched electron transfer events.