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

Abstract

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.

A Bioinspired Copper-Pair Catalyst in Metal–Organic Frameworks for Molecular Dioxygen Activation and Aerobic Oxidative C–N Coupling

“…Owing to the involvement of multiple metal sites that facilitate multi-electron transfer and spin transition, binuclear or trinuclear Cu centers are a major class of cofactors that bind and activate O 2 in many oxidases including cytochrome c oxidase, − tyrosinase, − catechol oxidase, − laccase, − etc. It has been long of interest mimicking the function of these oxidases in an artificial system and promoting aerobic oxygen utilization in organic reactions, − yet many of these artificial enzymes only exhibited limited activity and reaction/substrate scope so far.…”

Mask and Release Strategy‐Enabled Diversity‐Oriented Synthesis for DNA‐Encoded Library

“…[ 4 ] In the DEL library, each compound is connected to a unique, amplifiable DNA tag, simplifying chemical identification following selection against biomolecular targets. [ 5 ] So far, a series of hits have been efficiently selected from DELs, [ 6 ] targeting different types of drug targets such as enzymes, [ 7–13 ] kinase, [ 14 ] chemokines, [ 15 ] G protein‐coupled receptors (GPCRs), [ 16,17 ] protein and protein interactions (PPIs), [ 18–20 ] and RNA. [ 21–24 ] Furthermore, DEL has emerged became a fundamental platform to bridge chemistry and biology beyond the hit selection activity in innovative drug discovery.…”

Three-Stage Conversion of Chemically Inert n-Heptane to α-Hydrazino Aldehyde Based on Bioelectrocatalytic C–H Bond Oxyfunctionalization

“…36 Cai et al reported a cytochrome P450-mimetic metal organic framework that works in tandem with dehydrogenases, which is a photo-, chemo-, and biocatalytic hybrid, for C(sp 2 )−H functionalization. 37 In this study, we report a "three-stage (bioelectrocatalysis− biocatalysis−organocatalysis)" system that couples a bioelectrocatalytic multienzyme cascade with single amino acid-based organocatalysis for the sequential functionalization of nheptane to 1-heptanol, heptanal, and eventually the corre- sponding α-hydrazino aldehyde (Figure 1). The cathodic chamber contains an alkane monooxygenase (alkB, E C 1.14.15.3) from Pseudomonas putida GPO1, 38 a rubredoxin (alkG) protein from P. putida GPO1, 38 an engineered choline oxidase (AcCO 6 , E C 1.1.3.17) from Arthrobacter cholorphenolicus, 39 and a catalase (CatA, EC 1.11.1.6) from Bacillus subtilis.…”

“…Tandemly-used enzymes and photocatalysts (e.g., porphyrins and sodium AQ-2-sulfonate) have been reported for C–H hydroxylation, halogenation, amination, and ketone formation . Cai et al reported a cytochrome P450-mimetic metal organic framework that works in tandem with dehydrogenases, which is a photo-, chemo-, and biocatalytic hybrid, for C­(sp 2 )–H functionalization …”

“… 36 Cai et al reported a cytochrome P450-mimetic metal organic framework that works in tandem with dehydrogenases, which is a photo-, chemo-, and biocatalytic hybrid, for C(sp 2 )–H functionalization. 37 …”