Binding of Dual-Function Hybridized Metal–Organic Capsules to Enzymes for Cascade Catalysis

[Image: see text] The combination of chemo- and biocatalysis for multistep syntheses provides attractive advantages in terms of evolvability, promiscuity, and sustainability striving for desirable catalytic performance. Through the encapsulation of flavin analogues by both NADH and heme mimics codecorated heteroleptic metal–organic capsules, herein, we report a progressive host–guest strategy to imitate cytochrome P450s catalysis for cascade oxidative coupling catalysis. Besides the construction of stable dual-function metal–organic capsules and the modification of cofactor-decorated capsules at the domain of enzymes, this supramolecular strategy involves multistage directional electron flow, affording reactive ferric peroxide species for inducing oxygenation. Under light irradiation, the metal–organic capsule selectively converts stilbene to oxidative coupling products (including 2-oxo-1,2-diphenylethyl formate, 2-alkoxy-1,2-diphenylethanone) in tandem with enzymatic reactions respectively, at the domain of natural enzymes. The ingenious combination of capsules and enzymes with the in situ-regenerated capsule-loaded NADH cofactor promises non-native coupling reactions by forming regional cooperation and division. This abiotic–biotic conjugated host–guest strategy is conducive to the de novo creation of multifunctional components approaching active enzymatic sites for reinforced matter and energy transporting, demonstrating a key role of multicomponent supramolecular catalysts for one-pot integrated catalytic conversions.