近日，美国加州大学洛杉矶分校Soumitra V. Athavale团队实现了非活化烯烃的生物催化、不对称自由基加氢。相关论文于2025年10月16日发表在《科学》杂志上。

烯烃加氢是化学合成的基石，但酶的策略仍然局限于缺乏电子的底物通过氢化物转移。

利用血红素酶，研究组解锁了非活化烯烃不对称还原的加氢途径。硅烷促进活性位点血红素-半胱氨酸氧化还原循环，催化顺序氢原子转移到具有挑战性的支架，包括1,1-二取代、三取代和四取代烯烃。经过定向进化改造的酶具备广谱催化活性、氧耐受性，能利用地球储量丰富的铁元素，并可在常温常压下实现克级规模的合成。通过正交氢原子源策略，实现了位点发散的不对称同位素标记。机理研究与理论计算共同证实了该反应遵循分步进行的自由基机制。该工作介绍了立体选择性烯烃还原的生化方法，并为下一代生物催化加氢提供了平台。

附：英文原文

Title: Biocatalytic, asymmetric radical hydrogenation of unactivated alkenes

Author: Jaicy Vallapurackal, Rajib Mandal, Justin Bossenbroek, Aris V. Rubio, Ethan Poladian, James D. Collings, Cesar Torres, Matthew Hendrickson, Julian Morales, Max B. Lyons, Kyle Schultz, Hannah S. Shafaat, K. N. Houk, Soumitra V. Athavale

Issue&Volume: 2025-10-16

Abstract: Alkene hydrogenation is a cornerstone of chemical synthesis, yet enzymatic strategies remain limited to electron deficient substrates via hydride transfer. Using heme enzymes, we unlock a hydrogenation pathway for the asymmetric reduction of unactivated olefins. A silane promoted heme-cysteine redox cycle in the active site catalyzes sequential hydrogen atom transfer to challenging scaffolds including 1,1-disubstituted as well as tri- and tetrasubstituted alkenes. The evolved enzymes are promiscuous, oxygen-tolerant, utilize earth-abundant iron, and can operate on gram scale under ambient conditions. Orthogonal hydrogen atom sources enable site-divergent asymmetric isotope labeling. Mechanistic and computational studies support a stepwise radical process. Our work introduces a biochemical approach for stereoselective olefin reduction and provides a platform for next-generation biocatalytic hydrogenation.

DOI: aea4737

Source: https://www.science.org/doi/10.1126/science.aea4737