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

Angew Chem Int Ed Engl. 2024 Dec 15:e202419022. doi: 10.1002/anie.202419022. Online ahead of print.

Abstract

Genetically encodable photosensitizers allows for the design of artificial photoenzymes to expand the scope of abiological reactions. Here, we report the genetic incorporation of a thioxanthone-containing amino acid into a protein scaffold using 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 photoenzymatic reactions.

Keywords: artificial enzymes; biocatalysis; genetic code expansion; photocatalysis; thioxanthone.