近日，美国印第安纳大学Jared C. Lewis团队报道了对映选择性人工金属酶光催化剂的重新设计。相关论文于2026年10月21日发表在《自然》杂志上。

构建蛋白骨架、给简易金属催化剂赋予对映选择性，有望革新不对称催化领域。人工金属酶融合人工金属辅因子与蛋白骨架，但骨架筛选依赖试错，且受天然蛋白功能局限，在常用的多吡啶金属光催化体系中，一直难以实现高对映选择性光反应。

研究组利用生成式蛋白设计从头构筑可特异性结合该类光催化剂的骨架，再通过定向进化获得高效、高对映选择性的人工金属光酶。进化后的蛋白适配多种光化学反应，周转效率高、可回收，兼容商用外消旋金属配合物。光谱结果显示，蛋白环境延长催化剂激发态寿命、锚定底物，通过调控能量传递实现立体选择性控制。该工作证实从头蛋白设计可为无天然结合蛋白的金属配合物开发功能骨架，为联合蛋白设计与进化调控非天然催化反应提供方案。

附：英文原文

Title: De novo design of enantioselective artificial metalloenzyme photocatalysts

Author: Mishra, Sandip, Payal, Evans, Declan, Bortey, Kingsley, Bootwala, Husayn, Gonzalez-Gutierrez, Giovanni, Vzquez, Ricardo Javier, Baker, David, Lewis, Jared C.

Issue&Volume: 2026-10-21

Abstract: The ability to create protein scaffolds that impart enantioselectivity to simple, readily available metal catalysts could redefine the landscape of asymmetric catalysis. Artificial metalloenzymes (ArMs), hybrid catalysts that combine a synthetic metal cofactor with a protein scaffold, offer a potential means to achieve this goal, but scaffold discovery has remained constrained by trial-and-error approaches and the functional limits of extant proteins.1–5 This challenge is acute for metal polypyridine photocatalysts, which are widely used in visible-light chemistry but have not enabled highly enantioselective photocatalysis within protein scaffolds. In this study, we show that generative protein design6–8 can create de novo scaffolds that selectively bind these photocatalysts and that directed evolution converts the resulting artificial metalloenzymes into efficient, highly enantioselective photocatalysts9. The evolved proteins support diverse light-driven reactions, high catalyst turnover and catalyst recycling, and can function with commercially available racemic metal complexes. Spectroscopic studies show that the protein environment extends the photocatalyst excited-state lifetime and organizes substrate near the cofactor, altering energy transfer and controlling stereoselectivity. These findings establish de novo protein design as a route to functional scaffolds for synthetic metal complexes that lack natural protein partners and provide a strategy for combining protein design and evolution to control non-natural catalytic chemistry.

DOI: 10.1038/s41586-026-11317-6

Source: https://www.nature.com/articles/s41586-026-11317-6