Department of Biotechnology, National Institute of Technology, Warangal, India.
Department of Biotechnology, Sri Venkateswara College of Engineering, Sriperumbudur, India.
Biotechnol Appl Biochem. 2021 Dec;68(6):1518-1530. doi: 10.1002/bab.2073. Epub 2020 Nov 23.
Nitroreductases, enzymes found mostly in bacteria and also in few eukaryotes, use nicotinamide adenine dinucleotide (NADH) or nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor for their activity and metabolize an enormous list of a diverse nitro group-containing compounds. Nitroreductases that are capable of metabolizing nitroaromatic and nitro heterocyclic compounds have drawn great attention in recent years owing to their biotechnological, biomedical, environmental, and human impact. These enzymes attracted medicinal chemists and pharmacologists because of their prodrug selectivity for activation/reduction of nitro compounds that wipe out pathogens/cancer cells, leaving the host/normal cells unharmed. It is applied in diverse fields of study like prodrug activation in treating cancer and leishmaniasis, designing fluorescent probes for hypoxia detection, cell imaging, ablation of specific cell types, biodegradation of nitro-pollutants, and interpretation of mutagenicity of nitro compounds. Keeping in view the immense prospects of these enzymes and a large number of research contributions in this area, the present review encompasses the enzymatic reaction mechanism, their role in antibiotic resistance, hypoxia sensing, cell imaging, cancer therapy, reduction of recalcitrant nitro chemicals, enzyme variants, and their specificity to substrates, reaction products, and their applications.
硝基还原酶,主要存在于细菌中,也存在于少数真核生物中,其活性需要烟酰胺腺嘌呤二核苷酸(NADH)或烟酰胺腺嘌呤二核苷酸磷酸(NADPH)作为辅助因子,并代谢大量含硝基的化合物。近年来,能够代谢硝基芳烃和硝基杂环化合物的硝基还原酶因其在生物技术、生物医学、环境和人类方面的影响而受到广泛关注。这些酶吸引了药物化学家与药理学家的注意,因为它们对前药的选择性激活/还原可消灭病原体/癌细胞,而宿主/正常细胞不受伤害。它被应用于多种研究领域,如治疗癌症和利什曼病的前药激活、设计用于缺氧检测的荧光探针、细胞成像、特定细胞类型的消融、硝基污染物的生物降解以及对硝基化合物致突变性的解释。鉴于这些酶的巨大前景和该领域大量的研究贡献,本综述涵盖了酶的反应机制、它们在抗生素耐药性、缺氧感应、细胞成像、癌症治疗、难降解硝基化合物还原、酶变体及其对底物、反应产物的特异性以及它们的应用。