nitroreductase

Nitroreductases are a family of enzymes that catalyze the reductive transformation of nitro groups in nitroaromatic and nitroalkyl compounds. In many bacterial nitroreductases, the reaction uses NADPH or NADH as an electron donor and a flavin cofactor, typically flavin mononucleotide (FMN), to transfer electrons to the substrate. Reduction of a nitro group proceeds through nitroso and hydroxylamine intermediates and can continue to form an amine, with concomitant release of nitrite or water depending on the substrate.

Two functional classes are recognized in some studies: oxygen-insensitive (two-electron) nitroreductases and oxygen-sensitive (one-electron) nitroreductases. The former can operate under aerobic conditions and often reduce nitro groups fully to amines, whereas the latter generate radical intermediates that may react with oxygen. Most well-studied bacterial nitroreductases, such as Escherichia coli NfsA and NfsB, are flavoproteins that use FMN and prefer NADPH.

Biologically, nitroreductases participate in the microbial metabolism of nitroaromatic compounds, contributing to detoxification and to the degradation of environmental nitro pollutants. They are used in bioremediation research and as tools in synthetic biology.

In biotechnology, nitroreductases have been exploited for prodrug activation in cancer therapy (gene-directed enzyme prodrug therapy, or GDEPT), where a nitro-based prodrug is reduced to a cytotoxin in target tissues expressing the enzyme. They are also employed as reporter enzymes in cellular assays and as biocatalysts for the synthesis of reduced products.