Bacterial oxygen-insensitive NADPH nitroreductase (NTR)

Bacterial oxygen-insensitive NADPH nitroreductases, also known as Type I nitroreductases, are flavoenzymes that catalyze the reduction of nitroaromatic compounds (Williams et al., 2015, PubMed: 25853923). Unlike oxygen-sensitive Type II nitroreductases, these enzymes perform a direct two-electron reduction, which prevents the formation of superoxide radicals and allows them to function in aerobic environments (Roldan et al., 2008, PubMed: 18945487). In clinical practice, they are primarily known for activating prodrugs such as metronidazole and nitrofurantoin, which are used to treat bacterial and protozoal infections (UniProt: P0AAI4). Beyond their role in infectious diseases, these enzymes are a cornerstone of Gene-Directed Enzyme Prodrug Therapy (GDEPT) for cancer (Searle et al., 2004, PubMed: 15163119). In this context, bacterial genes like nfsB are delivered to tumor cells to convert non-toxic prodrugs like CB1954 into potent cytotoxic agents (Green et al., 2004, PubMed: 15256444). Their ability to selectively activate specific chemical moieties makes them valuable tools in both antimicrobial therapy and targeted oncology.

Other names

Type I nitroreductaseOxygen-insensitive nitroreductaseNfsANfsBNAD(P)H nitroreductaseMajor nitroreductaseMinor nitroreductase

These enzymes catalyze the obligatory two-electron reduction of nitro groups to hydroxylamines or amines using NAD(P)H as a cofactor (Williams et al., 2015, PubMed: 25853923). This process bypasses the formation of unstable nitro anion radicals, preventing the generation of reactive oxygen species in the presence of oxygen, which distinguishes them from Type II nitroreductases (Roldan et al., 2008, PubMed: 18945487).