Abstract
The scope of nature's catalytic abilities has been expanded by recent advancements in biocatalysis to include synthetic transformations with no biological equivalent. However, these newly introduced catalytic functions only represent a small fraction of reactions utilized in synthetic catalysis. This study presents a biocatalytic platform that combines photoredox and metalloenzymatic catalysis for enantioselective radical transformations. Under green light irradiation, the eosin Y photocatalyst enables 4-hydroxyphenylpyruvate dioxygenases (HPPD) to catalyse enantioselective decarboxylative azidation and thiocyanation of N-hydroxyphthalimide (NHPI) esters. The final optimized variant obtained through directed evolution can afford diverse chiral organic azide and thiocyanate compounds with up to 77% yield, 385 total turnovers, and 94% enantiomeric excess. Mechanistic studies show that the eosin Y catalyst mediates the generation of both C(sp(3)) radical and Fe(III)‒N(3)/Fe(III)‒NCS intermediate, leading to efficient enantioselective C‒N(3) and C‒SCN bond formation in the enzyme active site. These findings establish an adaptable biocatalytic platform for introducing abiological metallophotoredox catalysis into biology.