Cooperative catalysis with an enzyme and a small-molecule photocatalyst has very recently emerged as a potentially general activation mode to advance novel biocatalytic reactions with synthetic utility. Herein, we report cooperative photobiocatalysis involving an engineered nonheme Fe enzyme and a tailored photoredox catalyst as a unifying strategy for the catalytic enantioconvergent decarboxylative azidation, thiocyanation and isocyanation of redox-active esters via a radical mechanism. Through the survey and directed evolution of nonheme Fe enzymes, we repurposed and further evolved metapyrocatechase (MPC), a nonheme Fe extradiol dioxygenase not previously studied in new-to-nature biocatalysis, for the enantioselective C–N3, C–SCN and C–NCO bond formation through a radical rebound mechanism with an enzymatic Fe–X intermediate (X = N3, NCS, and NCO). A range of primary, secondary and tertiary alkyl radical precursors were effectively converted by our engineered MPC, allowing the syntheses of organic azides, thiocyanates and isocyanates with good to excellent enantiocontrol. Further chemical derivatization of these products furnished valuable compounds including enantioenriched amines, triazoles, ureas and SCF3-containing products. Computational studies via DFT and MD simulations shed light on the mechanism as well as the binding poses of the alkyl radical intermediate in the enzyme active site and the π-facial selectivity in the enantiodetermining radical rebound. Overall, cooperative photometallobiocatalysis with nonheme Fe enzymes provides a new platform for the development of challenging asymmetric radical transformations eluding small-molecule catalysis.

中文翻译：

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协同光金属生物催化实现非血红素 Fe 酶催化的对映体收敛自由基脱羧酰氮化、硫氰化和氧化还原活性酯的异氰化


酶和小分子光催化剂的协同催化最近已成为一种潜在的通用激活模式，以推进具有合成效用的新型生物催化反应。在此，我们报道了涉及工程非血红素 Fe 酶和定制光氧化还原催化剂的协同光生物催化，作为通过自由基机制对抗氧化活性酯的催化对映融合脱羧叠氮化、硫氰化和异氰化的统一策略。通过非血红素 Fe 酶的调查和定向进化，我们重新利用并进一步进化了偏焦聚 （MPC），一种以前未在新自然生物催化中研究过的非血红素 Fe 二醇外双加氧酶，用于对映选择性 C-N3、C-SCN 和 C-NCO 键的形成与酶 Fe-X 中间体（X = N3、NCS 和 NCO）。我们设计的 MPC 有效地转化了一系列伯、仲和叔烷基自由基前驱体，从而能够合成有机叠氮化物、硫氰酸盐和异氰酸酯，具有良好到优异的对映体控制。这些产品的进一步化学衍生化提供了有价值的化合物，包括对映体富集胺、三唑类、尿素和含 SCF3 的产品。通过 DFT 和 MD 模拟的计算研究阐明了烷基自由基中间体在酶活性位点的机制和结合姿势，以及对映决定自由基反弹的π面部选择性。总体而言，与非血红素 Fe 酶的协同光金属生物催化为开发具有挑战性的不对称自由基转化提供了一个新平台，避免了小分子催化。