Abstract: This study reports a novel photobiocatalytic system that integrates thiamine diphosphate (ThDP)-dependent enzymes with photoredox catalysis to achieve radical acylation between aromatic aldehydes and azonitrile reagents under visible light irradiation. This method enables the efficient synthesis of β-ketonitriles via cross-coupling of an enzyme-bound ThDP-derived ketyl radical and a photogenerated cyanoalkyl radical under mild conditions. The reaction exhibits a broad substrate scope and good functional group compatibility. This work represents the first example of synthesizing β-ketonitriles via photobiocatalysis, offering a new strategy for sustainable synthesis and expanding the toolbox for non-natural enzyme catalysis.

Key words: Photobiocatalysis, Radical acylation, ThDP, β-Ketonitriles