Skip to main content
SpringerLink
Log in

Derivatization of bioactive carbazoles by the biphenyl-degrading bacterium Ralstonia sp. strain SBUG 290

  • Biotechnological Products and Process Engineering
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Different 9H-carbazole derivatives have been investigated within the last decades due to their broad range of pharmacological applications. While the metabolism of 9H-carbazole has previously been reported, nothing was known about the bacterial transformation of 2,3,4,9-tetrahydro-1H-carbazole and 9-methyl-9H-carbazole. Thus, for the first time, the bacterial biotransformation of 2,3,4,9-tetrahydro-1H-carbazole and 9-methyl-9H-carbazole was analyzed using biphenyl-grown cells of Ralstonia sp. strain SBUG 290 expressing biphenyl 2,3-dioxygenase. This strain accumulated 3-hydroxy-1,2,3,5,6,7,8,9-octahydrocarbazol-4-one and 6′-iminobicyclohexylidene-2′,4′-dien-2-one as major products during the incubation with 2,3,4,9-tetrahydro-1H-carbazole. Carbazol-9-yl-methanol was verified as the primary oxidation product of 9-methyl-9H-carbazole. In addition, 9H-carbazol-1-ol, 9H-carbazol-3-ol, and 3-hydroxy-1,2,3,9-tetrahydrocarbazol-4-one where detected in lower concentrations during the transformation of carbazol-9-yl-methanol and 9-methyl-9H-carbazole. Products were identified by high-performance liquid chromatography, gas chromatography–mass spectrometry, liquid chromatography–mass spectrometry, as well as 1H and 13C nuclear magnetic resonance analyses.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Akalaeva TV, Amel’ki LYu, Baklanova OV, Bokanov AI, Ivanov PYu, Padeiskaya EN, Radkevich TP, Filitis LN, Shvedov VI (1990) Antitubercular, antifungal, and antibacterial activity in vitro of 1-phenethylamino-1,2,3,4-tetrahydrocarbazoles. Pharmaceut Chem J 24:826–829

    Article  Google Scholar 

  • Becher D, Specht M, Hammer E, Francke W, Schauer F (2000) Cometabolic degradation of dibenzofuran by biphenyl-cultivated Ralstonia sp. strain SBUG 290. Appl Environ Microbiol 66:4528–4531

    Article  CAS  Google Scholar 

  • Benedik MJ, Gibbs PR, Riddle RR, Willson RC (1998) Microbial denitrogenation of fossil fuels. Trends Biotechnol 16:390–395

    Article  CAS  Google Scholar 

  • Boyd DR, Sheldrake GN (1998) The dioxygenase-catalysed formation of vicinal cis-diols. Nat Prod Rep 15:309–325

    Article  CAS  Google Scholar 

  • Bregman H, Williams D, Meggers E (2005) Pyrido[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-diones: synthesis, cyclometalation, and protein kinase inhibition. Synthesis 9:1521–1527

    Google Scholar 

  • Bressler DC, Fedorak PM (2000) Bacterial metabolism of fluorene, dibenzofuran, dibenzothiophene, and carbazole. Can J Microbiol 46:397–409

    Article  CAS  Google Scholar 

  • Bruck P (1970) Studies on indoles, carbazoles, and related compounds. I. Carbazole leuco derivatives related to 4,4′-diaminodiphenylmethanes. Bis(3-carbazolyl)methanes and bis(9-carbazolyl) methanes. J Org Chem 35:2222–2227

    Article  CAS  Google Scholar 

  • Choi TA, Czerwonka R, Fröhner W, Krahl MP, Reddy KR, Franzblau SG, Knölker HJ (2006) Synthesis and activity of carbazole derivatives against Mycobacterium tuberculosis. ChemMedChem 1:812–815

    Article  CAS  Google Scholar 

  • Coutts RT, Jones GR, Benderly A, Temple DJ (1978) A comment on the formation of an N-hydroxymethyl intermediate in the metabolism of N-methylcarbazole. Xenobiotica 8:779–780

    Article  CAS  Google Scholar 

  • De Boer TD, Backer HJ (1956) Diazomethane. In: Leonard NJ (ed) Organic synthesis, vol. 36. Wiley, New York, pp 14–16

    Google Scholar 

  • Ferraro DJ, Gakhar L, Ramaswamy S (2005) Rieske business: structure–function of Rieske non-heme oxygenases. Biochem Biophys Res Commun 338:175–190

    Article  CAS  Google Scholar 

  • Gorrod JW, Temple DJ (1976) The formation of an N-hydroxymethyl intermediate in the N-demethylation of N-methylcarbazole in vivo and in vitro. Xenobiotica 6:265–274

    Article  CAS  Google Scholar 

  • Ha JD, Kang SK, Cheon HG, Choi JK (2004) Synthesis of tetrahydrocarbazole derivatives as potent β3-adrenoceptor agonists. Bull Korean Chem Soc 25:1784–1790

    Article  CAS  Google Scholar 

  • Hundt K, Wagner M, Becher D, Hammer E, Schauer F (1998) Effect of selected environmental factors on degradation and mineralization of biaryl compounds by the bacterium Ralstonia pickettii in soil and compost. Chemosphere 36:2321–2335

    Article  CAS  Google Scholar 

  • Ibe BO, Raj JU (1994) Metabolism of N-methylcarbazole by rat lung microsomes. Exp Lung Res 20:207–222

    Article  CAS  Google Scholar 

  • Kibal’nyi AV, Kharaneko OI, Dulenko VI (2001) New approach to ellipticine analogs. Chem Heterocycl Comp 37:1310–1311

    Article  Google Scholar 

  • Koop DR, Hollenberg PF (1980) Liver microsomal metabolism of N-methylcarbazole: a probe for induction, inhibition, and species differences. Mol Pharmacol 17:118–127

    CAS  PubMed  Google Scholar 

  • LaVoie EJ, Briggs G, Bedenko V, Hoffmann D (1982) Mutagenicity of substituted carbazoles in Salmonella typhimurium. Mutat Res 101:141–150

    Article  CAS  Google Scholar 

  • Li L, Li Q, Li F, Shi Q, Yu B, Liu F, Xu P (2006) Degradation of carbazole and its derivatives by a Pseudomonas sp. Appl Microbiol Biotechnol 73:941–948

    Article  CAS  Google Scholar 

  • Liger F, Popowycz F, Besson T, Picot L, Galmarini CM, Joseph B (2007) Synthesis and antiproliferative activity of clausine E, mukonine, and koenoline bioisosteres. Bioorg Med Chem 15:5615–5619

    Article  CAS  Google Scholar 

  • Martin AE, Prasad KJR (2006) Synthesis and characterization of carbazole derivatives and their antimicrobial studies. Acta Pharm 56:79–86

    CAS  PubMed  Google Scholar 

  • Meragelman KM, McKee TC, Boyd MR (2000) Siamenol, a new carbazole alkaloid from Murraya siamensis. J Nat Prod 63:427–428

    Article  CAS  Google Scholar 

  • Nojiri H, Habe H, Omori T (2001) Bacterial degradation of aromatic compounds via angular dioxygenation. J Gen Appl Microbiol 47:279–305

    Article  CAS  Google Scholar 

  • Novak RF, Koop DR, Hollenberg PF (1980) Liver microsomal metabolism of N-methylcarbazole: structural identification of the four major metabolites of N-methylcarbazole using 1H Fourier transform NMR spectroscopy. Mol Pharmacol 17:128–136

    CAS  PubMed  Google Scholar 

  • Resnick SM, Torok DS, Gibson DT (1993) Oxidation of carbazole to 3-hydroxycarbazole by naphthalene 1,2-dioxygenase and biphenyl 2,3-dioxygenase. FEMS Microbiol Lett 113:297–302

    Article  CAS  Google Scholar 

  • Sietmann R, Hammer E, Moody J, Cerniglia CE, Schauer F (2000) Hydroxylation of biphenyl by the yeast Trichosporon mucoides. Arch Microbiol 174:353–361

    Article  CAS  Google Scholar 

  • Traven VF, Plakhov VA, Stepanov BI (1967) Structure of the reaction products from carbazole or N-methylcarbazole and formaldehyde. Chem Heterocycl Compd 3:603–604

    Article  Google Scholar 

  • Waldau D, Methling K, Mikolasch A, Schauer F (2009) Characterization of new oxidation products of 9H-carbazole and structure related compounds by biphenyl-utilizing bacteria. Appl Microbiol Biotechnol 81:1023–1031

    Article  CAS  Google Scholar 

  • Wesche J, Hammer E, Becher D, Burchhardt G, Schauer F (2005) The bphC gene-encoded 2,3-dihydroxybiphenyl-1,2-dioxygenase is involved in complete degradation of dibenzofuran by the biphenyl-degrading bacterium Ralstonia sp. SBUG 290. J Appl Microbiol 98:635–645

    Article  CAS  Google Scholar 

  • Xu P, Yu B, Li FL, Cai XF, Ma CQ (2006) Microbial degradation of sulfur, nitrogen and oxygen heterocycles. Trends Microbiol 14:398–405

    Article  CAS  Google Scholar 

  • Yang W, Davis PJ (1992) Microbial models of mammalian metabolism. Biotransformations of N-methylcarbazole using the fungus Cunninghamella echinulata. Drug Metab Dispos 20:38–46

    PubMed  Google Scholar 

  • Yang W, Jiang T, Davis PJ, Acosta D (1991) In vitro metabolism and toxicity assessment of N-methylcarbazole in primary cultured rat hepatocytes. Toxicology 68:217–226

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the scholarship program of the German Federal Environmental Foundation (DBU).

Author information

Authors and Affiliations

  1. Institute of Microbiology and Molecular Biology, Department of Applied Microbiology, Ernst-Moritz-Arndt-University, Friedrich-Ludwig-Jahn-Straße 15, 17487, Greifswald, Germany

    Doreen Waldau, Annett Mikolasch & Frieder Schauer

  2. Institute of Pharmacy, Department of Biological Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany

    Michael Lalk

Authors
  1. Doreen Waldau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annett Mikolasch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Lalk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Frieder Schauer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Doreen Waldau.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Waldau, D., Mikolasch, A., Lalk, M. et al. Derivatization of bioactive carbazoles by the biphenyl-degrading bacterium Ralstonia sp. strain SBUG 290. Appl Microbiol Biotechnol 83, 67–75 (2009). https://doi.org/10.1007/s00253-008-1853-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-008-1853-z

Keywords

Search

Navigation