Chromophore–Peptide Construct for Synergistic Stabilization of Light-Exposed Enzymes

Abstract Light-induced deactivation severely limits the durability of enzymes operating under continuous irradiation, particularly heme- and flavin-dependent systems, whose cofactors directly absorb photons. Herein, we report a chromophore–peptide conjugate that self-assembles at enzyme surfaces to couple localized photon dissipation with conformational stabilization. A nonphotoisomerizable azobenzene unit was covalently grafted onto an oligolysine scaffold, enabling multivalent association with protein interfaces and spatial organization of photon-absorbing chromophores in close proximity to photoactive cofactors. This arrangement promotes efficient energy dissipation at reduced chromophore dosage while simultaneously stabilizing enzyme structure through cooperative electrostatic and hydrogen-bonding interactions. Encapsulation of the self-assembled complexes within hydrogen-bonded organic frameworks further affords recyclable hybrid biocatalysts. Using horseradish peroxidase and fatty acid photodecarboxylase as representative oxidoreductase and photoenzyme models, we demonstrate markedly enhanced stability under prolonged UV and blue-light irradiation, providing a proof-of-concept strategy for constructing light-resilient enzymatic materials.