A minireview on oxygen-insensitive nitroreductases: reaction mechanisms and their biomedical impact

Abstract

In this paper, we try to summarise some historically identified structural and catalytic properties of an important super-family of flavoenzymes, the oxygen-insensitive bacterial nitroreductases (NRs). We also review how these mechanistic properties have underpinned diverse roles in medicine and biomedical research, with an emphasis on the last decade. NRs perform the NAD(P)H-dependent two/four-electron reduction of nitroaromatic compounds (ArNO₂) and the two-electron reduction of quinones (Q) without the formation of free radicals of these compounds. This has significant implications for their behaviour in living systems. We reviewed the structural, catalytic and potentiometric properties of NRs and their oxidant substrate specificity, as well as the structural factors influencing it. Biomedical aspects of the function and application of NRs were also reviewed, including the importance of NRs in antibiotic resistance, their applications in cancer gene therapy, and NR-mediated cellular ablation technologies.