Bio-inspired electron-delivering system for reductive activation of dioxygen at metal centres towards artificial flavoenzymes

Abstract

Development of artificial systems, capable of delivering electrons to metal-based catalysts for the reductive activation of dioxygen, has been proven very difficult for decades, constituting a major scientific lock for the elaboration of environmentally friendly oxidation processes. Here we demonstrate that the incorporation of a flavin mononucleotide (FMN) in a water-soluble polymer, bearing a locally hydrophobic microenvironment, allows the efficient reduction of the FMN by NADH. This supramolecular entity is then capable of catalysing a very fast single-electron reduction of manganese(III) porphyrin by splitting the electron pair issued from NADH. This is fully reminiscent of the activity of natural reductases such as the cytochrome P450 reductases with kinetic parameters, which are three orders of magnitude faster compared with other artificial systems. Finally, we show as a proof of concept that the reduced manganese porphyrin activates dioxygen and catalyses the oxidation of organic substrates in water.

Riboflavin Directly Mediates the Dealkylation by Microbial Cytochrome P450 Monooxygeneses

“…Therefore, based on the structural features that, like widely existed microbial P450s, lack the reductase domain, we chose this microbial P450 as a model enzyme to probe its cofactor requirement, particu-13 larly whether riboflavin could substitute classic redox partner for the catalysis based on previous observations. [12][13][14][15][16] Surprisingly, HmtS indeed could directly utilize riboflavin and NADPH to accomplish the N-delakylation, showing higher efficiency than FAD and FMN. Further thorough comparison revealed that this finding is mediated by a new electron transfer pathway, which is not the same as any reported mechanisms for P450s.…”

Aerobic Baeyer–Villiger Oxidation Catalyzed by a Flavin‐Containing Enzyme Mimic in Water

“…Modified polyethyleneimines (PEI) are water‐soluble polymers known as good mimics for the local hydrophobic microenvironment of an enzyme′s active site . Using PEI modified with guanidinium and octyl groups, we previously showed that the incorporation of flavin mononucleotide (FMN) into such a microenvironment generated artificial flavoenzymes capable of collecting electrons from nicotinamide adenine dinucleotide (NADH) and then of reducing metallic cofactors under anaerobic conditions . Here, we demonstrate that under aerobic conditions, similar artificial flavoenzymes made of FMN incorporated into PEI, modified with guanidinium and octyl groups (FMN‐PEI guan‐oct ; Scheme ), catalyze the oxidation of NADH and perform aerobic BV reactions in water.…”

“…The FMN cofactor was then incorporated into the polymer thanks to the specific electrostatic interaction between the negatively charged phosphate groups and the guanidinium moieties. This incorporation of the FMN into the confined hydrophobic environment of the polymer was monitored by UV/Vis absorption spectroscopy, showing a characteristic 10 nm hypsochromic shift of the FMN band at 370 nm (Figure ) . Importantly, we also measured the absorption spectrum of FMN‐PEI guan‐oct in the presence of an excess of bicylo[3.2.0]hept‐2‐en‐6‐one as a potential substrate, and the same 10 nm shift was observed (Figure , red trace).…”

Nature is the Cure: Engineering Natural Redox Cofactors for Biomimetic and Bioinspired Catalysis

“…To overcome the challenge of providing the necessary electrons without quenching the active species, most synthetic systems use H 2 O 2 (hydrogen peroxide) as oxidizing agent and thus avoid the NADH/FMN couple altogether. Using a water‐soluble polyethyleneimine (PEI) polymer incorporating FMN units, Avenier and Mahy showed that a synzyme (synthetic enzyme) could be created to perform the role of a reductase enzyme . The PEI polymer is derivatized with guanidinium and octyl groups, thus offering binding for the FMN phosphate group while inducing a local hydrophobic environment.…”