Reductive Cytochrome P450 Reactions and Their Potential Role in Bioremediation.

James B Y H Behrendorff

doi:10.3389/fmicb.2021.649273

Abstract

Cytochrome P450 enzymes, or P450s, are haem monooxygenases renowned for their ability to insert one atom from molecular oxygen into an exceptionally broad range of substrates while reducing the other atom to water. However, some substrates including many organohalide and nitro compounds present little or no opportunity for oxidation. Under hypoxic conditions P450s can perform reductive reactions, contributing electrons to drive reductive elimination reactions. P450s can catalyse dehalogenation and denitration of a range of environmentally persistent pollutants including halogenated hydrocarbons and nitroamine explosives. P450-mediated reductive dehalogenations were first discovered in the context of human pharmacology but have since been observed in a variety of organisms. Additionally, P450-mediated reductive denitration of synthetic explosives has been discovered in bacteria that inhabit contaminated soils. This review will examine the distribution of P450-mediated reductive dehalogenations and denitrations in nature and discuss synthetic biology approaches to developing P450-based reagents for bioremediation.

Highlights

The late nineteenth and twentieth centuries saw explosive growth in the production and dissemination of halogenated and nitrated abiotic chemicals such as solvents, pesticides, and fire suppressants
This review focuses on known P450 enzymes (P450s)-mediated reductive dehalogenation and denitration reactions and discusses the potential for exploiting reductive P450 reactions in bioremediation
Further one-electron reductions of carbon trichloride result in a carbonyl dichloride radical that can inactivate the P450 directly or be hydrolysed to carbon monoxide (Li et al, 2014) (Figure 4A). This reaction cascade makes mammalian P450-mediated catabolism of carbon tetrachloride an interesting case study: by using reductive metabolism in hypoxic conditions the P450 can metabolise a toxic compound that cannot be metabolised via conventional oxidative P450 metabolism, but the products of reductive metabolism in this case pose a high risk of enzyme inactivation

Summary

Introduction

The late nineteenth and twentieth centuries saw explosive growth in the production and dissemination of halogenated and nitrated abiotic chemicals such as solvents, pesticides, and fire suppressants. Reductive dehalogenation and denitration reactions are initiated when an electron is transferred from the ferrous haem directly to the substrate, resulting in a substrate radical.

Results

Conclusion