Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA.
Institut de Química Computacional i Catàlisi (IQCC) and Departament de Química, Universitat de Girona, Campus Montilivi, Girona E-17071 Catalonia, Spain.
Science. 2022 May 20;376(6595):869-874. doi: 10.1126/science.abj2830. Epub 2022 May 19.
We report the reprogramming of nonheme iron enzymes to catalyze an abiological C(sp)‒H azidation reaction through iron-catalyzed radical relay. This biocatalytic transformation uses amidyl radicals as hydrogen atom abstractors and Fe(III)‒N intermediates as radical trapping agents. We established a high-throughput screening platform based on click chemistry for rapid evolution of the catalytic performance of identified enzymes. The final optimized variants deliver a range of azidation products with up to 10,600 total turnovers and 93% enantiomeric excess. Given the prevalence of radical relay reactions in organic synthesis and the diversity of nonheme iron enzymes, we envision that this discovery will stimulate future development of metalloenzyme catalysts for synthetically useful transformations unexplored by natural evolution.
我们报告了通过铁催化的自由基接力将非血红素铁酶重新编程以催化非生物 C(sp)‒H 叠氮化反应。这种生物催化转化使用酰基自由基作为氢原子提取剂和 Fe(III)‒N 中间体作为自由基捕获剂。我们建立了一个基于点击化学的高通量筛选平台，用于快速进化鉴定酶的催化性能。最终优化的变体提供了一系列叠氮化物产物，最高总转化率为 10600，对映体过量值为 93%。鉴于自由基接力反应在有机合成中的普遍性和非血红素铁酶的多样性，我们设想这一发现将刺激未来金属酶催化剂的发展，用于天然进化尚未探索的合成有用的转化。
