Bacterial nitroreductases and monoamine oxidase-like enzymes (NTR/MAO-like)

Bacterial nitroreductases (NTRs) and monoamine oxidase-like (MAO-like) enzymes are a group of flavin-dependent oxidoreductases that play critical roles in the metabolism of nitroaromatic and amine compounds. NTRs are primarily known for their ability to catalyze the reduction of nitro groups into highly reactive hydroxylamine or amino derivatives, a process exploited in the activation of several antimicrobial prodrugs such as nitrofurantoin and metronidazole. In addition to their role in treating bacterial and protozoal infections, NTRs are utilized in gene-directed enzyme prodrug therapy (GDEPT) to sensitize cancer cells to specific prodrugs. MAO-like enzymes in bacteria share structural similarities with human monoamine oxidases and are involved in the oxidative deamination of amines. Certain drugs, most notably furazolidone, interact with both enzyme types, acting as a prodrug substrate for NTRs while simultaneously inhibiting MAO activity. This dual interaction contributes to the drug's broad-spectrum antimicrobial efficacy but also necessitates caution regarding potential systemic side effects and drug-drug interactions.

Other names

NitroreductasesNTRsMonoamine oxidase-like proteinsFlavoenzymesType I nitroreductasesOxygen-insensitive nitroreductases

Reductive activation of nitro-containing prodrugs to cytotoxic intermediates (e.g., hydroxylamines and nitroso radicals) that damage DNA and proteins; Inhibition of monoamine oxidase activity.