华中科技大学吴钰周团队报道了三联体光酶对映选择性[2+2]环加成。相关研究成果于2022年9月21日发表于国际顶尖学术期刊《自然》。

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来运作。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，可以创造出扩大自然生物催化范围的人工光酶。

该文中，研究人员开发了嵌入能够激发态对映体诱导的合成三重态光敏剂的基因重组、化学进化的光酶。通过四轮定向进化进行的结构优化为吲哚衍生物的对映体选择性分子内[2+2]光环加成提供了对饮选择性变体，具有良好的底物通用性和优异的对映选择性（对映体过量高达99%）。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。

该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，为有价值的对映选择性光化学合成提供了一种综合方法，该合成无论是合成还是生物领域都无法单独实现。

附：英文原文

Title: Enantioselective [2+2]-cycloadditions with triplet photoenzymes

Author: Sun, Ningning, Huang, Jianjian, Qian, Junyi, Zhou, Taiping, Guo, Juan, Tang, Langyu, Zhang, Wentao, Deng, Yaming, Zhao, Weining, Wu, Guojiao, Liao, Rongzhen, Chen, Xi, Zhong, Fangrui, Wu, Yuzhou

Issue&Volume: 2022-09-21

Abstract: 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 enantioinduction4-6. 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 reactivity7-10 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.

DOI: 10.1038/s41586-022-05342-4

Source: https://www.nature.com/articles/s41586-022-05342-4