Bacterial oxygen-insensitive nitroreductase (NTR) (NTR)

Bacterial oxygen-insensitive nitroreductases (NTRs), also known as Type I nitroreductases, are flavin-dependent enzymes that play a pivotal role in the metabolism of nitroaromatic compounds (UniProt: P0AAI4). These enzymes utilize NAD(P)H to perform sequential two-electron reductions of nitro groups to hydroxylamines and amines. This process occurs independently of oxygen levels and avoids the generation of reactive oxygen species, distinguishing them from Type II nitroreductases (PMID: 17563306). In the context of infectious diseases, NTRs are the primary activators of several important antibiotics, such as metronidazole and nitrofurantoin, which are used to treat anaerobic bacterial and protozoal infections (PubChem: CID 4173). Beyond their role in antimicrobial therapy, NTRs are a cornerstone of Gene-Directed Enzyme Prodrug Therapy (GDEPT) in oncology (PMID: 21834913). In this approach, bacterial NTR genes, most commonly NfsB from Escherichia coli, are delivered to tumor cells to enable the localized conversion of non-toxic prodrugs like CB1954 into highly cytotoxic DNA-crosslinking agents. This dual utility makes NTRs significant targets for both the development of new antimicrobial agents and the refinement of targeted cancer therapies.

Other names

Type I nitroreductaseOxygen-insensitive nitroreductaseNfsANfsBMajor nitroreductase

Catalyzes the sequential two-electron reduction of nitro groups to hydroxylamine and amine derivatives using NAD(P)H as a cofactor, bypassing the production of superoxide radicals (PMID: 17563306).