1887

Abstract

-Demethylation of many xenobiotics and naturally occurring purine alkaloids such as caffeine and theobromine is primarily catalysed in higher organisms, ranging from fungi to mammals, by the well-studied membrane-associated cytochrome P450s. In contrast, there is no well-characterized enzyme for -demethylation of purine alkaloids from bacteria, despite several reports on their utilization as sole source of carbon and nitrogen. Here, we provide what we believe to be the first detailed characterization of a purified -demethylase from CBB5. The soluble -demethylase holoenzyme is composed of two components, a reductase component with cytochrome reductase activity (Ccr) and a two-subunit -demethylase component (Ndm). Ndm, with a native molecular mass of 240 kDa, is composed of NdmA (40 kDa) and NdmB (35 kDa). Ccr transfers reducing equivalents from NAD(P)H to Ndm, which catalyses an oxygen-dependent -demethylation of methylxanthines to xanthine, formaldehyde and water. Paraxanthine and 7-methylxanthine were determined to be the best substrates, with apparent and values of 50.4±6.8 μM and 16.2±0.6 min, and 63.8±7.5 μM and 94.8±3.0 min, respectively. Ndm also displayed activity towards caffeine, theobromine, theophylline and 3-methylxanthine, all of which are growth substrates for this organism. Ndm was deduced to be a Rieske [2Fe–2S]-domain-containing non-haem iron oxygenase based on (i) its distinct absorption spectrum and (ii) significant identity of the N-terminal sequences of NdmA and NdmB with the gene product of an uncharacterized caffeine demethylase in IF-3 and a hypothetical protein in sp. Marseille, both predicted to be Rieske non-haem iron oxygenases.

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2011-02-01
2024-03-28
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References

  1. Abel A. M., Carnell A. J., Davis J. A., Paylor M. 2003; The synthesis of buprenorphine intermediates by regioselective microbial N - and O -demethylation reactions using Cunninghamella echinulata NRRL 1384. Enzyme Microb Technol 33:743–748
    [Google Scholar]
  2. Altschul S. F., Madden T. L., Schäffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. 1997; Gapped blast and psi-blast: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402
    [Google Scholar]
  3. Asano Y., Komeda T., Yamada H. 1993; Microbial production of theobromine from caffeine. Biosci Biotechnol Biochem 57:1286–1289
    [Google Scholar]
  4. Asano Y., Komeda T., Yamada H. 1994; Enzymes involved in theobromine production from caffeine by Pseudomonas putida no. 352. Biosci Biotechnol Biochem 58:2303–2304
    [Google Scholar]
  5. Asha S., Vidyavathi M. 2009; Cunninghamella – a microbial model for drug metabolism studies – a review. Biotechnol Adv 27:16–29
    [Google Scholar]
  6. Blecher R., Lingens F. 1977; The metabolism of caffeine by a Pseudomonas putida strain. Hoppe Seylers Z Physiol Chem 358:807–817
    [Google Scholar]
  7. Bradford M. M. 1976; A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
    [Google Scholar]
  8. Buerge I. I., Poiger T., Muller M. D., Buser H. R. 2003; Caffeine, an anthropogenic marker for wastewater contamination of surface waters. Environ Sci Technol 37:691–700
    [Google Scholar]
  9. Capyk J. K., D'Angelo I., Strynadka N. C., Eltis L. D. 2009; Characterization of 3-ketosteroid 9 α -hydroxylase, a Rieske oxygenase in the cholesterol degradation pathway of Mycobacterium tuberculosis . J Biol Chem 284:9937–9946
    [Google Scholar]
  10. Caubet M. S., Comte B., Brazier J. 2004; Determination of urinary 13C-caffeine metabolites by liquid chromatography-mass spectrometry: the use of metabolic ratios to assess CYP1A2 activity. J Pharm Biomed Anal 34:379–389
    [Google Scholar]
  11. Cha C. J., Doerge D. R., Cerniglia C. E. 2001; Biotransformation of malachite green by the fungus Cunninghamella elegans . Appl Environ Microbiol 67:4358–4360
    [Google Scholar]
  12. Chang B., Chen Y., Zhao Y., Bruick R. K. 2007; JMJD6 is a histone arginine demethylase. Science 318:444–447
    [Google Scholar]
  13. Daly J. W. 2007; Caffeine analogs: biomedical impact. Cell Mol Life Sci 64:2153–2169
    [Google Scholar]
  14. Dash S. S., Gummadi S. N. 2006; Catabolic pathways and biotechnological applications of microbial caffeine degradation. Biotechnol Lett 28:1993–2002
    [Google Scholar]
  15. Dash S. S., Gummadi S. N. 2008; Inducible nature of the enzymes involved in catabolism of caffeine and related methylxanthines. J Basic Microbiol 48:227–233
    [Google Scholar]
  16. Dong X., Fushinobu S., Fukuda E., Terada T., Nakamura S., Shimizu K., Nojiri H., Omori T., Shoun H., Wakagi T. 2005; Crystal structure of the terminal oxygenase component of cumene dioxygenase from Pseudomonas fluorescens IP01. J Bacteriol 187:2483–2490
    [Google Scholar]
  17. Ensley B. D., Gibson D. T. 1983; Naphthalene dioxygenase: purification and properties of a terminal oxygenase component. J Bacteriol 155:505–511
    [Google Scholar]
  18. Fee J. A., Findling K., Yoshida T., Hille R., Tarr G., Hearshen D., Dunham W., Day E., Kent T., Münck E. 1984; Purification and characterization of the Rieske iron–sulfur protein from Thermus thermophilus . Evidence for a [2Fe–2S] cluster having non-cysteine ligands. J Biol Chem 259:124–133
    [Google Scholar]
  19. Ferraro D. J., Gakhar L., Ramasway S. 2005; Rieske business: structure–function of Rieske non-heme oxygenases. Biochem Biophys Res Commun 338:175–190
    [Google Scholar]
  20. Friemann R., Ivkovic-Jensen M. M., Lessner D. J., Yu C. L., Gibson D. T., Parales R. E., Eklund H., Ramaswamy S. 2005; Structural insight into the dioxygenation of nitroarene compounds: the crystal structure of nitrobenzene dioxygenase. J Mol Biol 348:1139–1151
    [Google Scholar]
  21. Glück M., Lingens F. 1988; Heteroxanthinedemethylase, a new enzyme in the degradation of caffeine by Pseudomonas putida . Appl Microbiol Biotechnol 28:59–62
    [Google Scholar]
  22. Guengerich F. P. 2001; Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem Res Toxicol 14:611–650
    [Google Scholar]
  23. Haigler B. E., Gibson D. T. 1990a; Purification and properties of ferredoxinNAP, a component of naphthalene dioxygenase from Pseudomonas sp. strain NCIB 9816. J Bacteriol 172:465–468
    [Google Scholar]
  24. Haigler B. E., Gibson D. T. 1990b; Purification and properties of NADH-ferredoxinNAP reductase, a component of naphthalene dioxygenase from Pseudomonas sp. strain NCIB 9816. J Bacteriol 172:457–464
    [Google Scholar]
  25. Hakil M., Denis S., Viniegra-Gonzalez G., Augur C. 1998; Degradation and product analysis of caffeine and related dimethylxanthines by filamentous fungi. Enzyme Microb Technol 22:355–359
    [Google Scholar]
  26. Jones S. B., Terry C. M., Lister T. E., Johnson D. C. 1999; Determination of submicromolar concentrations of formaldehyde by liquid chromatography. Anal Chem 71:4030–4033
    [Google Scholar]
  27. Kauppi B., Lee K., Carredano E., Parales R. E., Gibson D. T., Eklund H., Ramaswamy S. 1998; Structure of an aromatic-ring-hydroxylating dioxygenase-naphthalene 1,2-dioxygenase. Structure 6:571–586
    [Google Scholar]
  28. Koide Y., Nakane S., Imai Y. 1996; Caffeine demethylate gene-containing DNA fragment and microbial process for producing 3-methyl-7-alkylxanthine. United States patent US5550041
    [Google Scholar]
  29. Kvalnes-Krick K., Jorns M. S. 1986; Bacterial sarcosine oxidase: comparison of two multisubunit enzymes containing both covalent and noncovalent flavin. Biochemistry 25:6061–6069
    [Google Scholar]
  30. Lee K. 1995; Biochemical studies on toluene and naphthalene dioxygenases. PhD thesis University of Iowa;
    [Google Scholar]
  31. Lee C. 2000; Antioxidant ability of caffeine and its metabolites based on the study of oxygen radical absorbing capacity and inhibition of LDL peroxidation. Clin Chim Acta 295:141–154
    [Google Scholar]
  32. Madyastha K. M., Sridhar G. R. 1998; A novel pathway for the metabolism of caffeine by a mixed culture consortium. Biochem Biophys Res Commun 249:178–181
    [Google Scholar]
  33. Madyastha K. M., Sridhar G. R., Vadiraja B. B., Madhavi Y. S. 1999; Purification and partial characterization of caffeine oxidase-a novel enzyme from a mixed culture consortium. Biochem Biophys Res Commun 263:460–464
    [Google Scholar]
  34. Martins B. M., Svetlitchnaia T., Dobbek H. 2005; 2-Oxoquinoline 8-monooxygenase oxygenase component: active site modulation by Rieske-[2Fe–2S] center oxidation/reduction. Structure 13:817–824
    [Google Scholar]
  35. Mazzafera P., Olsson O., Sandberg G. 1996; Degradation of caffeine and related methylxanthines by Serratia marcescens isolated from soil under coffee cultivation. Microb Ecol 31:199–207
    [Google Scholar]
  36. Meskys R., Harris R. J., Casaite V., Basran J., Scrutton N. S. 2001; Organization of the genes involved in dimethylglycine and sarcosine degradation in Arthrobacter spp. Eur J Biochem 268:3390–3398
    [Google Scholar]
  37. Mohapatra B. R., Harris N., Nordin R., Mazumder A. 2006; Purification and characterization of a novel caffeine oxidase from Alcaligenes species. J Biotechnol 125:319–327
    [Google Scholar]
  38. Nishiya Y., Imanaka T. 1993; Cloning and sequencing of the sarcosine oxidase gene from Arthrobacter sp. TE1826. J Ferment Bioeng 75:239–244
    [Google Scholar]
  39. Ogunseitan O. 1996; Removal of caffeine in sewage by Pseudomonas putida : implications for water pollution index. World J Microbiol Biotechnol 12:251–256
    [Google Scholar]
  40. Phillips D. A., Sande E. S., Vriezen J. A. C., Bruijn F. J. d., Rudulier D. L., Joseph C. M. 1998; A new genetic locus in Sinorhizobium meliloti is involved in stachydrine utilization. Appl Environ Microbiol 64:3954–3960
    [Google Scholar]
  41. Rosche B., Tshisuaka B., Fetzner S., Lingens F. 1995; 2-Oxo-1,2-dihydroquinoline 8-monooxygenase, a two-component enzyme system from Pseudomonas putida 86. J Biol Chem 270:17836–17842
    [Google Scholar]
  42. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  43. Seiler R. L., Zaugg S. D., Thomas J. M., Howcroft D. L. 1999; Caffeine and pharmaceuticals as indicators of waste water contamination in wells. Ground Water 37:405–410
    [Google Scholar]
  44. Shi Y., Lan F., Matson C., Mulligan P., Whetstine J. R., Cole P. A., Casero R. A. 2004; Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119:941–953
    [Google Scholar]
  45. Sideso O. F. P., Marvier A. C., Katerelos N. A., Goodenough P. W. 2001; The characteristics and stabilization of a caffeine demethylase enzyme complex. Int J Food Sci Technol 36:693–698
    [Google Scholar]
  46. Smyth D. A. 1992; Effect of methylxanthine treatment on rice seedling growth. J Plant Growth Regul 11:125–128
    [Google Scholar]
  47. Subramanian V., Liu T., Yeh W., Gibson D. T. 1979; Toluene dioxygenase: purification of an iron-sulfur protein by affinity chromatography. Biochem Biophys Res Commun 91:1131–1139
    [Google Scholar]
  48. Tassaneeyakul W., Birkett D. J., McManus M. E., Tassaneeyakul W., Veronese M. E., Andersson T., Tukey R. H., Miners J. O. 1994; Caffeine metabolism by human hepatic cytochromes P450: contributions of 1A2, 2E1 and 3A isoforms. Biochem Pharmacol 47:1767–1776
    [Google Scholar]
  49. Tsukada Y., Fang J., Erdjument-Bromage H., Warren M. E., Borchers C. H., Tempst P., Zhang Y. 2006; Histone demethylation by a family of JmjC domain-containing proteins. Nature 439:811–816
    [Google Scholar]
  50. Ueda T., Lode E. T., Coon M. J. 1972; Enzymatic ω -oxidation. VI. Isolation of homogenous reduced diphosphopyridine nucleotide-rubredoxin reductase. J Biol Chem 247:2109–2116
    [Google Scholar]
  51. Wagner C. 1982; Cellular folate binding proteins; function and significance. Annu Rev Nutr 2:229–248
    [Google Scholar]
  52. Woolfolk C. A. 1975; Metabolism of N -methylpurines by a Pseudomonas putida strain isolated by enrichment on the caffeine as sole source of carbon and nitrogen. J Bacteriol 123:1088–1106
    [Google Scholar]
  53. Yu C. L., Liu W., Ferraro D. J., Brown E. N., Parales J. V., Ramaswamy S., Zylstra G. J., Gibson D. T., Parales R. E. 2007; Purification, characterization, and crystallization of the components of a biphenyl dioxygenase system from Sphingobium yanoikuyae B1. J Ind Microbiol Biotechnol 34:311–324
    [Google Scholar]
  54. Yu C. L., Kale Y., Gopishetyy S., Louie T. M., Subramanian M. 2008; A novel caffeine dehydrogenase in Pseudomonas sp. strain CBB1 oxidizes caffeine to trimethyluric acid. J Bacteriol 190:772–776
    [Google Scholar]
  55. Yu C. L., Louie T. M., Summers R., Kale Y., Gopishetty S., Subramanian M. 2009; Two distinct pathways for metabolism of theophylline and caffeine are coexpressed in Pseudomonas putida CBB5. J Bacteriol 191:4624–4632
    [Google Scholar]
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