Oxygen-insensitive NADPH nitroreductase (NfsA (for Escherichia coli), also NfsB or RdxA in other species[1][5][11])

Oxygen-insensitive NADPH nitroreductase is a bacterial enzyme primarily represented by NfsA and NfsB in Escherichia coli and RdxA in Helicobacter pylori, which catalyzes the reduction of nitroaromatic compounds—including important antibiotics and prodrugs—using NADPH or NADH as electron donors[1][5]. These enzymes are FMN-containing oxidoreductases that perform obligatory two-electron reductions, making them effective under aerobic conditions (“oxygen-insensitive”)[2][3][5]. They play critical roles in drug activation/detoxification, bacterial resistance to nitrodrugs, as well as potential applications in cancer gene therapy and bioremediation[7][8][10]. Their mechanism involves a ping-pong bi-bi reaction pathway, forming hydroxylamine or amine products[9][11]; they are widely distributed among bacteria and show broad substrate specificity. Loss or mutation of these enzymes can confer drug resistance, and their activity can produce toxic intermediates[1][2][5].

Other names

Oxygen-insensitive nitroreductaseNAD(P)H nitroreductaseNitroreductase type INfsA (Escherichia coli)NfsB (Escherichia coli)RdxA (Helicobacter pylori)[1][5][11]

Catalyzes two-electron reduction of nitro groups on aromatic/heterocyclic compounds using NADPH or NADH as electron donor, converting them to hydroxylamines or amines[2][5][9][10][11]