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 space^2-6. Elegant strategies, including directed evolution^7-10, artificial enzymes¹¹, and photoenzymatic catalysis^12,13 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 functions^14-16. 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.

电化学在合成化学领域正在复兴，并拥有令人信服的优势 ¹。通过合成化学策略重新利用天然酶为探索新的化学空间带来了巨大的前景 ^2-6。优雅的策略，包括定向进化 ^7-10、人工酶 ¹¹ 和光酶催化 ^12,13 已经证明了它们在学术界和工业界扩展酶应用的能力。然而，电化学与酶的整合主要限于复制先前建立的酶功能 ^14-16。实现新酶与电的反应性的主要挑战包括兼容性问题和异质电子转移的困难。在这里，我们报道了用二茂铁介导的电催化重塑硫胺素依赖性酶以解锁α支链醛的非自然动态动力学氧化。这种强大的电酶方法可产生各种生物活性 （S）-profens，对映体过量高达 99%，适用于过表达酶并使用低至 0.05 mol% 酶载量的全细胞。机理研究揭示了电酶在精确底物鉴别中的多种功能，加速外消旋化，并促进动力学匹配的电子转移事件。