Dehydrogenation, oxidative denitration and ring contraction of N,N-dimethyl-5-nitrouracil by a Bacillus nitroreductase Nfr-A1

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• 作者：Sylvie Cortial^a ; Philippe Chaignon^a ; Didier Sergent^a ; Sophie Dezard^b ; Jamal Ouazzani^a ; ^{jamal.ouazzani@icsn.cnrs-gif.fr}
• 关键词：Nitroreductase ; NADH-oxidase ; Nitrouracil ; Denitration ; Ring contraction
• 刊名：Journal of Molecular Catalysis B: Enzymatic
• 出版年：2012
• 出版时间：April, 2012
• 年：2012
• 卷：76
• 期：Complete
• 页码：1-8
• 全文大小：1012 K

文摘

Nfr-A1, a Bacillus subtilis nitroreductase, catalyzes the nitroreduction of a large panel of aromatic and heterocyclic nitro compounds, except those belonging to nitrouracil class of molecules. Besides nitroreduction, Nfr-A1 exhibits a strong NADH oxidase activity in the presence of oxygen, leading to high concentration of H₂O₂ (up to 200 ¦ÌM). In the presence of (N,N)-dimethyl-5-nitrouracil 1 (dim-NU), Nfr-A1 achieves the reduction of dim-NU double bond to compounds 2 and 3 and in parallel the oxidation of dim-NU to the denitrated five membered derivatives 4 and 5. The reduction is catalyzed by the reduced flavin Fl-_Red and resembles those catalyzed by dihydropyrimidine dehydrogenases (DPD), during the catabolism of pyrimidines. The oxidative denitration is catalyzed in part by hydrogen peroxide generated through the NADH-oxidase activity, and certainly by the peroxyflavin intermediate Fl-_OOH for the other part. The mechanisms of reaction were proposed according to experimental data and literature. These findings together with our previous results on the potential biological role of Nfr-A1, confirm the large spectrum of catalysis supported by this enzyme. The oxidative denitration is sporadically reported in literature and represents a safe and green alternative for the remediation of nitro-compounds.