Roldán María Dolores, Pérez-Reinado Eva, Castillo Francisco, Moreno-Vivián Conrado
Departamento de Bioquímica y Biología Molecular, Campus de Rabanales, Universidad de Córdoba, Córdoba, Spain.
FEMS Microbiol Rev. 2008 May;32(3):474-500. doi: 10.1111/j.1574-6976.2008.00107.x. Epub 2008 Mar 18.
Most nitroaromatic compounds are toxic and mutagenic for living organisms, but some microorganisms have developed oxidative or reductive pathways to degrade or transform these compounds. Reductive pathways are based either on the reduction of the aromatic ring by hydride additions or on the reduction of the nitro groups to hydroxylamino and/or amino derivatives. Bacterial nitroreductases are flavoenzymes that catalyze the NAD(P)H-dependent reduction of the nitro groups on nitroaromatic and nitroheterocyclic compounds. Nitroreductases have raised a great interest due to their potential applications in bioremediation, biocatalysis, and biomedicine, especially in prodrug activation for chemotherapeutic cancer treatments. Different bacterial nitroreductases have been purified and their biochemical and kinetic parameters have been determined. The crystal structure of some nitroreductases have also been solved. However, the physiological role(s) of these enzymes remains unclear. Nitroreductase genes are widely spread within bacterial genomes, but are also found in archaea and some eukaryotic species. Although studies on regulation of nitroreductase gene expression are scarce, it seems that nitroreductase genes may be controlled by the MarRA and SoxRS regulatory systems that are involved in responses to several antibiotics and environmental chemical hazards and to specific oxidative stress conditions. This review covers the microbial distribution, types, biochemical properties, structure and regulation of the bacterial nitroreductases. The possible physiological functions and the biotechnological applications of these enzymes are also discussed.
大多数硝基芳香族化合物对生物体具有毒性和致突变性，但一些微生物已进化出氧化或还原途径来降解或转化这些化合物。还原途径要么基于通过氢化物加成使芳香环还原，要么基于将硝基还原为羟氨基和/或氨基衍生物。细菌硝基还原酶是黄素酶，可催化硝基芳香族和硝基杂环化合物上的硝基进行依赖于NAD(P)H的还原反应。由于硝基还原酶在生物修复、生物催化和生物医学中的潜在应用，尤其是在化疗癌症治疗的前药激活方面，它们引起了极大的关注。不同的细菌硝基还原酶已被纯化，并测定了它们的生化和动力学参数。一些硝基还原酶的晶体结构也已得到解析。然而，这些酶的生理作用仍不清楚。硝基还原酶基因在细菌基因组中广泛分布，但在古菌和一些真核生物物种中也有发现。尽管关于硝基还原酶基因表达调控的研究很少，但似乎硝基还原酶基因可能受MarRA和SoxRS调控系统控制，这两个系统参与对多种抗生素、环境化学危害以及特定氧化应激条件的响应。本综述涵盖了细菌硝基还原酶的微生物分布、类型、生化特性、结构和调控。还讨论了这些酶可能的生理功能和生物技术应用。
