南京大学黄小强团队近日研究了电力驱动的酶的动态动力学氧化。相关论文于2025年5月28日发表在《自然》杂志上。

电化学在合成化学中正在复苏，并具有令人信服的优势。通过合成化学策略重新利用天然酶对探索新的化学空间具有重要的前景。包括定向进化、人工酶和光酶催化在内的简明策略已经证明了它们在学术界和工业界扩大酶应用的能力。然而，电化学与酶的结合主要局限于复制先前建立的酶功能。实现新的酶与电反应性的关键挑战包括相容性问题和异质电子转移的困难。

研究组报告了用二茂铁介导的电催化重塑硫胺素依赖酶，以解锁α-支化醛的非自然动态动力学氧化。这种强大的电酶方法产生各种生物活性（S）-脯氨酸，其对映体过量高达99%，适用于过表达酶的全细胞，并使用低至0.05 mol%的酶负载。机理研究揭示了电酶在精确区分底物、加速外消旋化和促进动力学匹配的电子转移事件方面的多种功能。

附：英文原文

Title: Electricity-driven enzymatic dynamic kinetic oxidation

Author: Zhao, Beibei, Xu, Yuanyuan, Zhu, Qin, Liu, Aokun, Peng, Xichao, Zhang, Tianying, Yu, Lu, Zhang, Yan, Huang, Xiaoqiang

Issue&Volume: 2025-05-28

Abstract: Electrochemistry is undergoing a resurgence in synthetic chemistry and boasts compelling advantages1. Repurposing natural enzymes through synthetic chemical strategies holds significant promise for exploring new chemical space2-6. Elegant strategies, including directed evolution7-10, 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 functions14-16. 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 α-branched aldehydes. This robust electroenzymatic approach yields various bioactive (S)-profens with up to 99% enantiomeric excess, is applicable with whole cells overexpressing the enzyme and using down to 0.05 mol% enzyme loadings. Mechanistic investigations reveal multiple functions of the electroenzyme in the precise substrate discrimination, accelerating racemization, and facilitating kinetically matched electron transfer events.

DOI: 10.1038/s41586-025-09178-6

Source: https://www.nature.com/articles/s41586-025-09178-6