Beyond Flavoproteins: Toward the Industrialization of Photobiocatalysis

Photobiocatalysis merges enzymatic selectivity with the synthetic versatility of light, enabling complex transformations under mild, aqueous conditions. However, advances in this field remain primarily focused on the adaptation of native flavoproteins and known oxidoreductases, such as ene-reductases, with limited exploration of non-natural cofactors or engineered proteins. This perspective examines the current progress in photobiocatalysis, in addition to design constraints that limit the scope of photobiocatalysis, including narrow cofactor compatibility, short excited-state lifetimes, and the instability of enzyme–chromophore systems under irradiation. We highlight the overreliance on a small subset of light-responsive enzyme complexes and propose a broader, modular framework for photoenzyme development. By dissecting the interplay between chromophore identity, protein structure, and reaction environment, we outline strategies to extend the reactivity, stability, and tunability of photoenzymes beyond their native roles. Together, these strategies provide a blueprint for the systematic design, benchmarking, and application of photobiocatalytic systems for broader use and industrial applications.