Naturally evolved enzymes, despite astonishingly large variety and function diversity, operate predominantly through thermochemical activation. Integrating prominent photocatalysis modes into proteins such as triplet energy transfer could create artificial photoenzymes that expand the scope of natural biocatalysis.^1-3 Here, we exploit genetically reprogrammed, chemically evolved photoenzymes embedded with a synthetic triplet photosensitizer that are capable of excited state enantioinduction^4-6. Structural optimization through four rounds of directed evolution afforded proficient variants for the enantioselective intramolecular [2+2] photocycloaddition of indole derivatives with good substrate generality and excellent enantioselectivities (up to 99% enantiomeric excess). A crystal structure of the photoenzyme-substrate complex elucidated the noncovalent interactions which mediate reaction stereochemistry. This study expands the energy transfer reactivity^7-10 of artificial triplet photoenzymes in a supramolecular protein cavity and unlocks an integrated approach to valuable enantioselective photochemical synthesis that is not accessible with either the synthetic or the biological world alone.

自然进化的酶，尽管种类繁多，功能多样，但主要通过热化学活化作用发挥作用。将突出的光催化模式整合到蛋白质中，例如三重态能量转移，可以创造出扩大天然生物催化范围的人工光酶。^1-3在这里，我们利用嵌入了合成三重态光敏剂的基因重编程、化学进化的光酶，这些光敏剂能够激发态对映诱导^4-6. 通过四轮定向进化进行的结构优化为吲哚衍生物的对映选择性分子内 [2+2] 光环加成提供了熟练的变体，具有良好的底物通用性和出色的对映选择性（高达 99% 的对映体过量）。光酶-底物复合物的晶体结构阐明了介导反应立体化学的非共价相互作用。这项研究扩展了超分子蛋白质空腔中人工三重态光酶的能量转移反应性^{7-10 ，并开启了一种有价值的对映选择性光化学合成的综合方法，这是合成或生物世界无法单独实现的。}