Reduction of polynitroaromatic compounds: the bacterial nitroreductases

Abstract

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.

Response of antimicrobial nitrofurazone-degrading biocathode communities to different cathode potentials

“…Previous studies have found that Enterococcus is often enriched in the nitroaromatic nitrobenzene-reducing biocathode communities, and the relative abundance can reach 38.4% or 74.7% (Wang et al, 2011). This was consistent with the fact that Enterococcus and Pseudomonas species own nitroaromaticsreducing ability (Rafii et al, 2003;Roldan et al, 2008). These results indicated that the microbial community structure with applied electrical stimulation was obviously different from that of the open circuit biofilm.…”

“…A recent study has found that Citrobacter was obviously enriched by 29.24% in a glucose-fed azo dye-reducing biocathode community (Sun et al, 2016). Relatively low abundances of Desulfovibrio (from 1.63 to 2.04% in the electrode biofilms), Salmonella (from 0.14 to 1.17% in the electrode biofilms) and Clostridium (4.35% in the open circuit biofilm) were also detected, which have been reported to carry out nitroaromatics reduction by nitroreductase (Roldan et al, 2008;Spain, 1995). Collectively, cathode potential regulation strategy stimulated the microbial electrode respiration activity, and enriched different electroactive respectively.…”

“…Klebsiella was dominant in the 0.2 V (accounting for 62.54%) and 0.5 V (accounting for 56.96%) applied groups, while it was obviously decreased to 6.36% in the 0.8 V supply group. Previous studies have demonstrated that Klebsiella has nitroaromatics-reducing ability and electrochemical activity (Roldan et al, 2008;Xia et al, 2010). The 0.8 V supply group and open circuit control mainly enriched Enterococcus (accounting for 56.34%) and Pseudomonas (accounting for 81.82%), respectively.…”

Identification of novel nitroreductases from Bacillus cereus and their interaction with the CB1954 prodrug

“…It was shown that both the 11 BC_1619 and BC_3024 enzymes followed a ping pong bi bi reaction mechanism . Taken together, the 12 two novel proteins from B. cereus were classified as oxygen-insensitive nitroreductases, based on the 13 following characteristics: reduce nitro-groups to hydroxylamine derivatives in presence of oxygen; 14 follow a ping pong bi bi mechanism; require NADH or NADPH as cofactors; are homodimers; contain 15 a FMN prosthetic group; and are strongly inhibited by dicoumarol [47,48,49]. 16 In order to decide on names that most closely described the two novel proteins, both homology 17 searching and biochemical characterisations were used to rename the B. cereus enzymes.…”

Caco-2 cells cytotoxicity of nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA)

“…The toxic effects are related to the electrophilic character of these derivatives, while the mutagenic effects are mainly due to the formation of hydroxylamine adducts resulting from esterification with the nucleic acid guanine. Additionally, some nitroaromatic compounds are intrinsically toxic and function as uncouplers of oxidative phosphorylation, inhibiting the generation of the proton motive force required for ATP synthesis (Roldán et al, 2008).…”