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

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.