Abstract
Flavins and pteridines act as catalysts in many hydroxylation reactions, particularly those in bacterial systems. One atom of dioxygen is incorporated in the hydroxyl group and the other is reduced to water, so these enzymes are monooxygenases. Flavin monooxygenases (for a review, see Ballou, 1982) perform aromatic hydroxylations, oxidative decarboxylations, and oxidation of amines. Flavin monooxygenases are not able to hydroxylate aliphatic hydrocarbons, and most, if not all, aromatic substrates are fairly well activated by hydroxy or amino groups.
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References
Ando, W., Miyazaki, H., and Kohmoto, S., 1979. Oxygen atom transfer by an intermediate in the photosensitized oxygenation of diazo compounds, Tetrahedron Lett. 1317–1320.
Ball, S., and Bruice, T.C., 1979. 4a-Hydroperoxyflavin N-oxidation of teriary amines, J. Am. Chem. Soc. 101: 4017–4019.
Ball, S., and Bruice, T.C., 1980. Oxidation of amines by 4a-hydroperoxyflavin, J. Am. Chem. Soc. 102: 6498–6503.
Ball, S., and Bruice, T.C., 1981. The chemistry of 1-carba- 1-deaza-N5-methyl lumiflavins: Influence of the N1 upon the reactivity of flavin 4a-hydroperoxides, J. Am. Chem. Soc. 103: 5494–5503.
Ballou, D.P., 1982. Flavin monooxygenases, Dev. Biochem. 21: 301–310.
Bartlett, P. D., and Traylor, T. G., 1962. Reaction of diphenyldiazomethane with oxygen: The Criegee carbonyl oxide, J. Am. Chem. Soc. 84: 3488–3409.
Beaty, N. B., and Ballou, D.P., 1980. Transient kinetic study of liver microsomal FAD-containing monooxygenase, J. Biol. Chem., 255: 3817–3819.
Beaty, N. B., and Ballou, D.P., 1981. The oxidative half-reaction of liver microsomal FADcontaining monooxygenase, J. Biol. Chem. 256: 4619–4625.
Chiriboga, J., 1966. Purification and properties of oxalic acid oxidase, Arch. Biochem. Biophys. 116: 516–523.
Chuang, H.Y. K., Patek, D.R., and Hellerman, L., 1974. Mitochondrial monoamine oxidase inactivation by pargyline: Adduct formation, J. Biol. Chem. 249: 2381.
Detmar, K., Massey, V., Ballou, D.P., and Neujahr, H.Y., 1982. Steady state and rapid reaction studies on phenol hydroxylases, Dev. Biochem. 21: 334–338.
Donoghue, N.A., Norris, D. B., and Trudgill, P. W., 1976. The purification and properties of cyclohexanone oxygenase from Nocardia globerula CL I and Acinetobactor NCIB 9871, Eur. J. Biochem. 63: 175–192.
Entsche, B., Massey, V., and Ballou, D.P., 1974. Intermediates in flavoprotein catalyzed hydroxylation, Biochem. Biophys. Res. Commun. 57: 1018–1026.
Entsche, B., Ballou, D.P., and Massey, V., 1976. Flavin-oxygen derivatives involved in hydroxylation by p-hydroxybenzoate hydroxylase, J. Biol. Chem. 251: 2550–2563.
Entsche, B., Hussain, M., Ballou, D.P., Massey, V., and Walsh, C., 1980. Oxygen reactivity of p-hydroxybenzoate hydroxylase containing 1-deazaflavin, J. Biol. Chem. 255: 1420–1429.
Flashner, M. I. S., and Massey, V., 1974. Purification and properties of L-lysine monooxygenase from Pseudomonas fluorescens, J. Biol., Chem. 249: 2579–2586.
Frost, J.W., and Rastetter, W. H., 1981. Flavoprotein monooxygenase: A chemical model, J. Am. Chem. Soc. 103: 5242–5245.
Hajjar, N. P., and Hodgson, E., 1980. Flavin adenine dinucleotide-dependent monooxygenase: Its role in the sulfoxidation of pesticides in mammals, Science 209: 1134–1136.
Hamilton, G. A., 1971. The proton in biological redox reactions, Prog. Bioorg. Chem. 1: 83–157.
Hamilton, G. A., and Giacin, J.R., 1966. Oxidations by molecular oxygen. III. Oxidation of saturated hydrocarbons by an intermediate in the reaction of some carbenes with oxygen, J. Am. Chem. Soc. 88: 1584–1585.
Hamzah, R. Y., and Tu, S.-C., 1981. Determination of the position of monooxygenation in the formation of catechol catalyzed by salicylate hydroxylase, J. Biol. Chem. 256: 6392–6394.
Hayaishi, O., and Sutton, W.B., 1957. Enzymatic oxygen fixation into acetate concomitant with the enzymatic decarboxylation of L-lactate, J. Am. Chem. Soc. 79: 4809–4810.
Hayaishi, O., Tabor, H., and Hayaishi, T., 1957. N-Formimino-L-aspartic acid as an intermediate in the enzymatic conversion of imidazole-acetic acid to formylaspartic acid, J. Biol. Chem. 227: 161–180.
Hellerman, L., and Erwin, V.G., 1968. Mitochondrial amine oxidase. II. Action of various inhibitors for the bovine kidney enzyme catalytic mechanism, J. Biol. Chem. 243: 5234–5243.
Howell, L. G., and Massey, V., 1970. A non-substrate effector of p-hydroxybenzoate hydroxylase, Biochem. Biophys. Res. Commun. 40: 887–893.
Howell, L. G., Spector, T., and Massey, V., 1972. Purification and properties of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens, J. Biol. Chem. 247: 4340–4350.
Husain, M., Schapfer, L. M., and Massey, V., 1978. p-Hydroxybenzoate hydroxylase and melilotate hydroxylase, Methods Enzymol. 53: 543–558.
Itada, N., Ichihara, A., Makita, T., Hayaishi, O., Suda, M., and Sasaki, N., 1961. L-Lysine oxidase, a new oxygenase, J. Biochem. 50: 118–121.
Kamin, H., White-Stevens, R.H., and Presswood, R.P., 1978. Salicylate hydroxylase, Methods Enzymol. 53: 527–543.
Katagiri, M., and Takenori, S., 1971. The Reaction mechanism of flavin-containing enzymes, in Flavins and Flavoproteins, H. Kamin (ed.), University Park Press, Baltimore, Maryland, pp. 447–462.
Kemal, C., and Bruice, T.C., 1976. Simple synthesis of a 4a-hydroperoxy adduct of a 1,5dihydroflavin: Preliminary studies of a model for bacterial luciferase, Proc. Nad. Acad. Sci. U.S.A. 73: 995–999.
Kemal, C., Chan, T. W., and Bruice, T.C., 1977. Reaction of 302 with dihydroflavins. I. N 3,s_ Dimethyl-1,5-dihydrolumiflavin and 1,5-dihydroisoalloxazines, J. Am. Chem. Soc. 99: 7272–7286.
Kirmse, W., Norner, L., and Hoffman, H., 1958. Umsetzungen photochemisch erzeugter Carbene, Annalen 614: 19–30.
Kumar, R.P., Ravindranath, S. D., Vaidyanathan, C.S., and Rao, N.A., 1972. Mechanism of hydroxylation of aromatic compound. II. Evidence for the involvement of superoxide anions in enzymatic hydroxylations, Biochem. Biophys. Res. Commun. 49: 1422–1426.
Lockridge, O., Massey, V., and Sullivan, P.A., 1972. Mechanism of action of the flavoenzyme lactate oxidase, J. Biol. Chem. 247: 8098–8106.
Maki, Y., Yamamoto, S., Nozaki, M., and Hayaishi, O., 1966. Crystallization of imidazoleacetate monooxygenase and its characterization as a flavoprotein, Biochem. Biophys. Res. Commun. 25: 609–613.
Maki, T., Yamamoto, S., Nozaki, M., and Hayaishi, O., 1969. Studies of monooxygenase. II. Crystallization and some properties of imidazole and acetate monooxygenase, J. Biol. Chem. 244: 2942–2950.
Massey, V., and Hemmerich, P., 1975. Flavin and pteridine monooxygenases, in The Enzymes, Vol. 12, P. D. Boyer (ed.), Academic Press, New York, pp. 191–252.
Maycock, A. L., Abeles, R.H., Salach, J. I., and Singer, R.P., 1976. The structure of the covalent adduct formed by the interaction of 3-dimethylamino- l -propyne and the flavine of mitochondrial amine oxidase, Biochemistry 15: 114–125.
McIntire, W., Edmondson, D. F., and Singer, T.P., 1980. 8α-O-Tryosyl-FAD: A new form of covalently bound flavin from p-cresol methyl hydroxylase, J. Biol. Chem. 255: 6553–6555.
McIntire, W., Edmondson, D. E., Hopper, D. J., and Singer, T.P., 1981. 8a-(0-Tyrosyl) flavin adenine dinucleotide, the prosthetic group of bacterial p-cresol methylhydroxylase, Biochemistry 20: 3068–3075.
Nakazawa, T., Hori, K., and Hayaishi, O., 1972. Studies on monooxygenases. V. Manifestation of amino acid oxidase activity by L-lysine monooxygenase, J. Biol. Chem. 247: 3439–3444.
Nanni, E. J., Jr., Sawyer, D. T., Ball, S. S., and Bruice, T.C., 1981. Redox chemistry of N5-ethyl-3-methyl-lumiflavinium cation and NS-ethyl-4a-hydroperoxy-3-methyllumiflavin in dimethylformamide: Evidence for the formation of the Ns-ethyl-4a-hydroperoxy-3-methyllumiflavin anion via radical-radical coupling with superoxide ion, J.-Am. Chem. Soc. 103: 2797–2802.
Neujahr, H.Y., and Gaal, A., 1973. Phenol hydroxylase from yeast: Purification and properties of the enzyme from Trichosporon cutaneum, Ev. J. Biochem. 35: 386–400.
Okamoto, H., Nozaki, M., and Hayaishi, O., 1968. A role of sulfhydryl groups in imidazoleacetate monooxygenase, Biochem. Biophys. Res. Commun. 32: 30–36.
Orf, H. W., and Dolphin, D., 1974. Oxaziridines as possible intermediates in flavin monooxygenases, Proc. Nad. Acad. Sci. U.S.A. 71: 2646–2650.
Ortha, Y., and Ribbons, D.W., 1970. Crystallization of orcinol hydroxylase from Pseudomonas putida, FEES Lett. 2: 189–192.
Paulsen, L. L., and Ziegler, D.M., 1979. The liver microsomal FAD-containing monooxygenase, J. Biol. Chem. 254: 6449–6455.
Pho, D. B., Olomucki, A., and Thoai, N.V., 1966. L-Arginine oxygenase decarboxylante. IV. Incorporation de 18O dans la -y-guanidino-butryamide, Biochim. Biophys. Acta 118: 311–315.
Premkumar, R., Roa, R. V. S., Sreeleela, N. S., and Vaidyanathan, C.S., 1969. m-Hydroxybenzoic acid 4-hydroxylase from Asperigillus niger, Can. J. Biochem. 47: 825–827.
Rastetter, W. H., Gadek, T. R., Tane, J. P., and Frost, J.W., 1979. Oxidations and oxygen transfers effected by a flavin N(5)-oxide: A mode for flavin-dependent monooxygenases, J. Am. Chem. Soc. 101: 2228–2231.
Rothberg, S., and Hayaishi, O., 1957. Studies on oxygenases: Enzymatic oxidation of imidazoleacetic acid, J. Biol. Chem. 229: 897–903.
Ryerson, R. R., Ballou, D.P., and Walsh, C. 1982. Kinetic isotope effects in the oxidation of isotopically labeled NAD(P)H by bacterial flavoprotein monooxygenases, Biochemistry 21: 1144–1151.
Schopfer, L. M., and Massey, V., 1980. Kinetic and mechanistic studies on the oxidation of the melilotate hydroxylase 2-OH-cinnamate complex by molecular oxygen, J. Biol. Chem. 255: 5355–5363.
Schwab, J. M., 1981. Stereochemistry of an enzymatic Baeyer-Villiger reaction: Application of deuterium NMR, J. Am. Chem. Soc. 103: 1876–1879.
Shoun, H., and Beppu, T., 1982. A histidine residue in p-hydroxybenzoate hydroxylase essential for binding of reduced nicotinamide adenine dinucleotide phosphate, J. Biol. Chem. 257: 3422–3428.
Shoun, H., Beppu, T., and Arima, K., 1980. An essential arginine residue at the substrate-binding site of p-hydroxybenzoate hydroxylase, J. Biol. Chem. 255: 9319–9324.
Spector, T., and Massey, V., 1972a. p-Hydroxybenzoate hydroxylase from Pseudomonas fluorescens: Evidence for an oxygenated flavin intermediate, J. Biol. Chem. 247: 5632–5636.
Spector, T., and Massey, V., 1972b. Studies on the effector specificity of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens, J. Biol. Chem. 247: 6479–6487.
Spector, T., and Massey, V., 1972c. p-Hydroxybenzoate hydroxylase from Pseudomonas fluorescens: Reactivity with oxygen, J. Biol. Chem. 247: 7123–7127.
Steenis, P. G., Cordes, M. M., Hilkens, G.-H., and Muller, F., 1973. On the interaction of parahydroxybenzoate hydroxylase from Pseudomonas fluorescens with halogen ions, FEES Lett. 36: 177–180.
Strickland, S., and Massey, V., 1973. The purification and properties of the flavoprotein melilotate hydroxylase, J. Biol. Chem. 248: 2944–2952.
Strickland, S., and Massey, V., 1973b. The mechanism of action of the flavoprotein melilotate hydroxylase, J. Biol. Chem. 248: 2953–2962.
Strickland, S., Schopfer, L. M., and Massey, M., 1975. Kinetics and mechanistic studies on the reaction of melilotate hydroxylase with deuterated melilotate, Biochemistry 14: 2230–2235.
Suzuki, K., and Katagiri, M., 1981. Mechanism of salicylate hydroxylase-catalyzed decarboxylation, Biochim. Biophys. Acta 657: 530–534.
Takeda, H., Yamamoto, S., Kojima, V., and Hayaishi, O., 1969. Studies on monooxygenases. I. General properties of crystalline L-lysine monooxygenase, J. Biol. Chem. 244: 2935–2941.
Takemori, S., Nakamura, M., Suzuki, K., Katagiri, M., and Nakamura, T., 1972. Mechanism of the salicylate hydroxylase reactioN.V. Kinetic analysis, Biochim. Biophys. Acta 284: 382–393.
Tokumura, K., Goto, H., Kashiwabara, H., Kaneko, C., and Itoh, H., 1980. Formation and reaction of oxaziridine intermediate in the photochemical reaction of 6-cyano phenanthridine 5-oxide at low temperature, J. Am. Chem. Soc. 102: 5643–5647.
Walsh, C. T., Schonbrun, A., Lockridge, O., Massey, V., and Abeles, R.H., 1972. Inactivation of a flavoprotein lactate oxidase by an acetylenic substrate, J. Biol. Chem. 247: 6004–6006.
Walsh, C. T., Lockridge, 0., Massey, V., and Abeles, R.H., 1973. Studies on the mechanism of action of the flavoenzyme lactic oxidase: Oxidation and elimination with R-chloroacetate, J. Biol. Chem. 248: 7049–7054.
Wang, L.-H., Hamzah, R.H., and Tu, S.C., 1982. On the mechanism of salicylate hydroxylase: Studies using deuterated substrates, Dev. Biochem. 21: 346–349.
Wessiak, A., and Bruice, T.C., 1981. On the nature of the intermediate between 4a-hydroperoxyflavin and 4a-hydroxyflavin in the hydroxylation reaction of p-hydroxybenzoate hydroxylase: Synthesis of 6-aminopyrimidine-2,4,5(34)-triones and the mechanism of aromatic hydroxylation by flavin monooxygenases, J. Am. Chem. Soc. 103: 6996–6998.
White-Stevens, R.H., and Kamin, H., 1972. Studies of a flavoprotein: Salicylate hydroxylase. II. Enzyme mechanism, J. Biol. Chem. 247: 2371–2381.
Wierenga, R. K., de Jong, R. J., Kalk, K. H., Hol, W. G. J., and Drenth, J., 1979. Crystal structure of p-hydroxybenzoate hydroxylase, J. Mol. Biol. 131: 55–73.
Yamauchi, T., Yamamoto, S., and Hayaishi, O., 1973. Reversible conversion of lysine monooxygenase to an oxidase by modification of sulfhydryl groups, J. Biol. Chem. 248: 3750–3752.
Yamamoto, S., Nakazawa, T., and Hayaishi, O., 1972. Studies on monooxygenases. IV. Anaerobic formation of an α-keto acid by L-lysine monooxygenase, J. Biol. Chem. 247: 3434–3438.
Ziegler, D.M., and Mitchell, C.H., 1972. Microsomal oxidase. IV. Properties of a mixed-function amine oxidase isolated from pig liver microsomes, Arch. Biochem. Biophys. 150: 116–125.
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© 1985 Plenum Press, New York
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Ingraham, L.L., Meyer, D.L. (1985). Flavin Monooxygenases. In: Biochemistry of Dioxygen. Biochemistry of the Elements, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2475-1_12
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DOI: https://doi.org/10.1007/978-1-4613-2475-1_12
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