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用于设计人工光酶的含噻吨酮氨基酸的基因掺入。

Genetic Incorporation of a Thioxanthone-Containing Amino Acid for the Design of Artificial Photoenzymes.

作者信息

Chen Kai-Yue, Ming Hui, Wang He-Xiang, Wang Hua-Qi, Xiang Zheng

机构信息

State Key Laboratory of Chemical Oncogenomics, Shenzhen Key Laboratory of Chemical Genomics, AI for Science (AI4S) Preferred Program, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, University Town of Shenzhen, Nanshan District, 518055 Shenzhen, P. R. China.

Institute of Chemical Biology, Shenzhen Bay Laboratory, Gaoke Innovation Center, Guangqiao Road, Guangming District, 518132 Shenzhen, P. R. China.

出版信息

Angew Chem Int Ed Engl. 2025 Jan 27;64(5):e202419022. doi: 10.1002/anie.202419022. Epub 2025 Jan 2.

Abstract

Genetically encodable photosensitizers allow the design of artificial photoenzymes to expand the scope of abiological reactions. Herein, we report the genetic incorporation of a thioxanthone-containing amino acid into a protein scaffold via an engineered pyrrolysyl-tRNA/pyrrolysyl-tRNA synthetase pair. The designer enzyme was engineered to catalyze a dearomative [2+2] cycloaddition reaction in high yields (up to>99 % yield) with excellent enantioselectivity (up to 98 : 2 e.r.). This work provides a robust and facile method for photoenzyme design and lays the foundation for the development of further photoenzymatic reactions.

摘要

基因编码的光敏剂能够设计人工光酶,从而拓展非生物反应的范围。在此,我们报告了通过工程化的吡咯赖氨酸 - tRNA/吡咯赖氨酸 - tRNA合成酶对,将含噻吨酮的氨基酸基因整合到蛋白质支架中。这种设计的酶经过工程改造,能够以高产率(高达>99%产率)和优异的对映选择性(高达98:2 e.r.)催化脱芳构化[2+2]环加成反应。这项工作为光酶设计提供了一种强大且简便的方法,并为进一步开发光酶促反应奠定了基础。

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