Designing and Engineering Enzymes for New-to-Nature Photobiocatalysis.

Photobiocatalysis, an interdisciplinary frontier integrating chemistry, biology, and catalysis, drives enzymatic catalysis from natural reactions to new-to-nature transformations via protein engineering and photochemistry. This review centers on enzyme classes, covering nine key families: fatty acid photodecarboxylases (FAPs), nicotinamide-dependent reductases, flavin-dependent "ene"-reductases (EREDs), and others like artificial photoenzymes. We detail photoenzymatic development, mechanisms, and protein engineering for reactivity expansion. Despite enzymes' superior stereocontrol, their reaction scope is narrower than small-molecule catalysts. Future exploration of universal activation mechanisms and AI-assisted engineering will expand photobiocatalysis' potential for sustainable chiral synthesis and green chemistry.