Reduction of Nitroaromatic Explosives by Oxygen-Insensitive NAD(P)H:Nitroreductases: Implications for their Cytotoxicity and Biodegradation

• Autorzy: Misevičiene, L. , Nivinskas, H. , Anusevičius, Z. , Čenas, N. , Nemeikaite-Čeniene, A. , Maldutis, E. , Harris, R. J. , Scrutton, N. S.
• Języki publikacji: EN

Abstrakty

EN

Nitroaromatic explosives are toxic and mutagenic to humans and other mammalian species. The first step(s) in the biodegradation/bioremediation of the explosive residues in soil or groundwater is their reduction by bacterial oxygeninsensitive nitroreductases to the relatively stable metabolites. Here we analyze the quantitative structure-activity relationships in the reduction of nitroaromatic explosives and model nitroaromatic compounds by mammalian DT-diaphorase (NQO1) and Enterobacter cloacae NAD(P)H:nitroreductase (NR), which performs the four-electron reduction of nitrogroups to corresponding hydroxylamines, and by Enterobacter cloacae PB2 NADPH: pentaerythritol tetranitrate reductase (PETNR), which performs nitroreduction and reduction of benzene ring with the formation of hydride-Meisenheimer adducts. Our data show that in all the cases the reduction rate of nitroaromatics mainly depends on the energetics of the charge transfer.

Słowa kluczowe

EN

nitroaromatic explosives; enzymatic reduction; biodegradation

• Czasopismo: Central European Journal of Energetic Materials
• Rocznik: 2006
• Tom: Vol. 3, nr 4
• Strony: 89-101
• Opis fizyczny: Bibliogr. 26 poz.

Twórcy

autor

Misevičiene, L.

autor

Nivinskas, H.

autor

Anusevičius, Z.

autor

Čenas, N.

autor

Nemeikaite-Čeniene, A.

autor

Maldutis, E.

autor

Harris, R. J.

autor

Scrutton, N. S.

• Institute of Biochemistry, Mokslininku 12, LT-08662 Vilnius, Lithuania,

Bibliografia

• [1] Kong I., Jiang Q., Qu Q., Formation of Superoxide Radical and Hydrogen Peroxide Enhanced by Trinitrotoluene in Rat Liver, Brain, Kidney, and Testicle in Vitro and Monkey Liver in Vivo, Biomed. Environ. Set., 1989, 2, 72-77.
• [2] Cenas N., Nemeikaite-Ceniene A., Sergediene E., Nivinskas H., Anusevic'ius Z., Sarlauskas J., Quantitative Structure-Activity Relationships in Enzymatic Single-Electron Reduction of Nitroaromatic Explosives: Implications for their Cytotoxiciry, Biochim. Biophys. Acta, 2001,1528, 31-38.
• [3] Orna M. V., Mason R. P., Correlation of Kinetic Parameters of Nitroreductase Enzymes with Redox Properties of Nitroaromatic Compounds, J. Biol. Chem., 1989,264. 12379-12384.
• [4] Leung K. H., Yao M., Stearns R,, Chiu S-H. L., Mechanism of Bioactivationand Covalent Binding of 2,4,6-Trinitrotoluene, Chem.-Biol. Interact., 1995, 97, 37-51.
• [5] Spain J. C., Biodegradation of nitroaromatic compounds, Annu. Rev. Microbiol, 1995, 49, 523-555.
• [6] Sarlauskas J., Dickancaite E., Nemeikaite A., Anusevicius Z., Nivinskas H., Segura-Aguilar J., Cenas N., Nitrobenzimidazoles as Substrates for DT-Diaphorase and Redox Cycling Compounds: Their Enzymatic Reactions and Cytotoxicity, Arch. Biochem. Biophys., 1997, 346, 219-229.
• [7] Nivinskas H., Koder R. L., Anusevicius Z., Sarlauskas J., Miller A.-F., Cenas N., Quantitative Structure-Activity Relationships in Two-Electron Reduction of Nitroaromatic Compounds by Enterobacter Cloacae NAD(P)H:Nitroreductase, ibid,2QQl, 385, 170-178.
• [8] Sarlauskas J., Nemeikaite-Ceniene A., Anusevicius Z., Miseviciene L., Martinez-Julvez M., Medina M., Gomez-Moreno C., Cenas N., Flavoenzyme-Catalyzed Redox Cycling of Hydroxylamino- and Amino Metabolites of 2,4,6-Trinitrotoluene: Implications for their Cytotoxicity, ibid, 2004, 425, 184-192.
• [9] Sarlauskas J., Nemeikaite-Ceniene A., Anusevicius Z., Miseviciene L., Maroziene A., Markevicius A., Cenas N., Enzymatic Redox Properties of Novel Nitrotetrazole Explosives: Implications for their Toxicity, Z. Naturforsck., 2004, 59c, 399-404.
• [10] Nemeikaite-Ceniene A., Sarlauskas J., Miseviciene L., Anusevicius Z., Maroziene A., Cenas N., Enzymatic Redox Reactions of the Explosive 4,6-Dinitrobenzofuroxan (DNBF): Implications for its Toxic Action, Ada Biochim. Polon., 2004, 5,7,1081 -1086.
• [11] Miseviciene L., Anusevicius Z., Sarlauskas J., Cenas N., Reduction of Nitroaromatic Compounds by NAD(P)H:Quinone Oxidoreductase (NQO1): the Role of Electron-Accepting Potency and Structural Parameters in the Substrate Specificity, ibid, 2006, 53, 569-576.
• [12] Tedeschi G., Chen S., Massey V, DT-Diaphorase. Redox Potential, Steady-State, and Rapid Reaction Studies, J. Biol. Chem., 1995,270, 1198-1204.
• [13] Anusevicius Z., Sarlauskas J., Cenas N., Two-electron Reduction of Quinones by Rat Liver NAD(P)H:Quinone Oxidoreductase: Quantitative Structure-activity relationships, Arch. Biochem. Biophys., 2002, 404, 254-262.
• [14] Bianchet M. A., Faig M., Amzel L. M., Structure and Mechanism of NAD(P)H: Quinone Acceptor Oxidoreductase (NQO), Meth. Enzymol., 2004, 382B, 144-174.
• [15] Skelly J. V, Sanderson M. R., Suter D. A., Baumann U., Read M. A., Gregory D. S. J., Bennett M., Hobbs S. M., Neidle S., Crystal Structure of Human DT-Diaphorase: A Model for Interaction with the Cytotoxic Prodrug 5-(Aziridin-l-yl)-2,4-dinitrobenzamide (CB 1954), J. Med. Chem., 1999, 42, 4325-4330.
• [16] Chen S., Wu K., Zhang D., Sherman M., Knox R., Yang C. S., Molecular Characterization of Binding of Substrates and Inhibitors to DT-Diaphorase: Combined Approach Involving Site-Directed Mutagenesis, Inhibitor-Binding Analysis, and Computer Modeling, Mol. Pharmacol., 1999, 56, 272-278.
• [17] Koder R. L., Haynes C. A., Rodgers M. E., Rodgers D. W., Miller A. F., Flavin Thermodynamics Explain the Oxygen Insensitivity of Enteric Nitroreductases, Biochemistry, 2002, 41, 14197-14205.
• [18] Race P. R., Levering A. L., Green R. M., Ossor A., White S. A., Searle P. F., Wrighton C. J., Hyde E. L, Structural and Mechanistic Studies of Escherichia Coli Nitroreductase with the Antibiotic nitrofurazone. Reversed Binding Orientations in Different Redox States of the Enzyme, /. Biol Chem., 2005, 280, 13256-13264.
• [19] Haynes C. A., Koder R. L., Miller A. F., Rodgers D. W., Structures of Nitroreductase in Three States: Effects of Inhibitor Binding and Reduction, ibid., 2002, 277, 11513-11520.
• [20] Khan H., Barna T., Harris R. J., Bruce N. C., Barsukov L, Munro A. W., Moody P. C. E., Scrutton N. S., Atomic Resolution Structures and Solution Behavior of Enzyme-Substrate Complexes of Enterobacter cloacae PB2 Pentaerythritol Tetranitrate Reductase, ibid., 2004, 279, 30563-30572.
• [21] Williams R. E., Rathbone D. A., Scrutton N. S., Bruce N. C., Biotransformation of Explosives by the Old Yellow Enzyme Family of Flavoproteins, Appl. Environ. Miocrobiol., 2004, 70, 3566-3574.
• [22] Pak J. W., Knoke K. L., NogueraD. R., Fox B. G., Chambliss G. H., Transformation of 2,4,6-Trinitrotoluene by Purified Xenobiotic Reductase B from Pseudomonas fluorescens 1-C, Appl. Environ. MicrobioL, 2000, 66, 4742-4750.
• [23] French C. E., Rosser S. J., Davies G. J., Nicklin S., Bruce N. C., Biodegradation of Explosives by Transgenic Plants Expressing Pentaerythritol Tetranitrate Reductase, Nat. Biotechnol, 1999,17, 491-494.
• [24] Khan H., Harris R. J., Barna T., Craig D. H., Bruce N. S., Munro A. W., Moody P. C. E., SruttonN. S., Kinetic and Structural Basis of Reactivity of Pentaerythritol Tetranitrate Reductase with NADPH, 2-Cyclohexenone, Nitroesters, and Nitroaromatic Explosives, J. Biol. Chem., 2002, 277, 21906-21912.
• [25] Lachance B., Robidoux P. Y., Hawari J., Ampleman G., Thiboutot S., Sunahara G. I., Cytotoxic and Genotoxic Effects of Energetic Compounds on Bacterial and Mammalian Cells in Vitro, Mutat. Res., 1999, 444, 25-39.
• [26] Honcycutt M. E., Jarvis A. S., McFarland V. A., Cytotoxicity and Mutagenicity of 2,4,6-Trinitrotoluene and Its Metabolites, Ecotoxicol. Environ. Saf., 1996, 35, 282-287-