Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Studies on Microbial Transformation of Meloxicam by Fungi

  • Shyam Prasad, G. (Department of Microbiology, Kakatiya University) ;
  • Girisham, S. (Department of Microbiology, Kakatiya University) ;
  • Reddy, S.M. (Department of Microbiology, Kakatiya University)
  • Published : 2009.09.30
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Abstract

Screening-scale studies were performed with 26 fungal cultures for their ability to transform the anti-inflammatory drug meloxicam. Among the different fungi screened, a filamentous fungus, Cunninghamella blakesleeana NCIM 687, transformed meloxicam to three metabolites in significant quantities. The transformation of meloxicam was confirmed by high-performance liquid chromatography (HPLC). Based on the liquid chromatography-tandem mass spectrometry (LC-MS/MS) data, two metabolites were predicted to be 5-hydroxymethyl meloxicam and 5-carboxy meloxicam, the major mammalian metabolites reported previously. A new metabolite was produced, which is not detected in mammalian systems. Glucose medium, pH of 6.0, temperature of $27^{\circ}C$, 5-day incubation period, dimethylformamide as solvent, and glucose concentration of 2.0% were found to be suitable for maximum transformation of meloxicam when studied separately. It is concluded that C. blakesleeana can be employed for biotransformation of drugs for production of novel metabolites.

Keywords

References

  1. Alarcon, J., J. B. Alderete, S. Aguila, and M. Peter. 2005. Regio and stereo selective hydroxylation of A-Agarofuran by biotransformation of Rhizopus nigricans. J. Chil. Chem. Soc. 50: 715-718 https://doi.org/10.4067/S0717-97072005000400012
  2. Azerad, R. 1999. Microbial models for drug metabolism. Adv. Biochem. Eng. Biotechnol. 63: 169-218 https://doi.org/10.1007/3-540-69791-8_8
  3. Mobic ${\circledR}$. Product Information. Boehringer Ingelheim Taiwan Ltd., Taiwan
  4. Breiter, S., D. Schlosser, D. Weiss, and H.P. Schmouder. 1995. Microbial hydroxylation of androst-1, 4-dien-3, 17-dione. Nat. Prod. Lett. 6: 7-14 https://doi.org/10.1080/10575639508044081
  5. Busch, U., J. Schmid, G. Heinzel, and H. Schmaus. 1998. Pharmacokinetics of meloxicam in animal with relevance to humans. Drug Metab. Dispos. 26: 576-584
  6. Cha, C. J., D. R. Doerge, and C. E. Cerniglia. 2001. Biotransformation of malachite green by the fungus Cunninghamella elegans. Appl. Environ. Microbiol. 67: 4358-4360 https://doi.org/10.1128/AEM.67.9.4358-4360.2001
  7. Chatterjee, T. and D. K. Bhattacharyya. 2001. Biotransformation of limonene by Pseudomonas putida. Appl. Microbiol. Biotechnol. 55: 541-546 https://doi.org/10.1007/s002530000538
  8. Chesne, C., C. Guyomard, A. Guillouzo, J. Schmid, E. Ludwig, and T. Sauter. 1998. Metabolism of meloxicam in human liver involves cytochrome P4502C9 and 3A4. Xenobiotica 28: 1-13 https://doi.org/10.1080/004982598239704
  9. Churchill, L., A. Graham, C. K. Shih, D. Pauletti, P. R. Farina, and P. M. Grob. 1996. Selective inhibition of human cyclooxygenase 2 by meloxicam. Inflam. Pharm. 4: 125-135 https://doi.org/10.1007/BF02735467
  10. Dai, Y. J., S. Yuan, F. Ge, T. Chen, S. C. Xu, and J. P. Ni. 2006. Microbial hydroxylation of imidacloprid for the synthesis of highly insecticidal olefin imidacloprid. Appl. Microbiol. Biotechnol. 71: 927-934 https://doi.org/10.1007/s00253-005-0223-3
  11. Elbary, A. A., N. Foda, and M. Elkhateeb. 2001. Reversed phase liquid chromatographic determination of meloxicam in human plasma and its pharmacokinetic application. Anal. Lett. 34: 1175-1187 https://doi.org/10.1081/AL-100104963
  12. Engelhardt, G., R. B$\ddot{o}$gel, C. H. R. Schnitzler, and R. Utzmann. 1996. Meloxicam: Influence on arachidonic acid metabolism. I. In vitro findings. Biochem. Pharmacol. 51: 21-28 https://doi.org/10.1016/0006-2952(95)02111-6
  13. Faramarzi, M. A., M. T. Yazdi, H. Jahandar, M. Amini, and H. R. Monsef-Esfahani. 2006. Studies on the microbial transformation of androst-1, 4-dien-3, 17-dione with Acremonium strictum. J. Ind. Microbiol. Biotechnol. 33: 725-733 https://doi.org/10.1007/s10295-006-0135-y
  14. Faramarzi, M. A., M. T. Yazdi, M. Amini, G. Zarrini, and A. Shafiee. 2003. Microbial hydroxylation of progesterone with Acremonium strictum. FEMS Microbiol Lett. 222: 183-186 https://doi.org/10.1016/S0378-1097(03)00257-X
  15. Grifoll, M., M. Casellas, J. M. Bayona, and A. M. Solanas. 1992. Isolation and characterization of a fluorine degrading bacterium: Identification and ring oxidation and ring fission products. Appl. Environ. Microbiol. 58: 2910-2917
  16. Guruswamy, S., V. Kumar, and D. N. Mishra. 2006. Preparation and evaluation of solid dispersion of meloxicam with skimmed milk. Pharm. Soc. Japan 126: 93-97 https://doi.org/10.1248/yakushi.126.93
  17. Hanson, R. L., J. A. Matson, D. B. Brzozowski, T. L. Laporte, D. M. Springer, and R. N. Patel. 2002. Hydroxylation of mutilin by Streptomyces griseus and Cunninghamella echinulata. Org. Proc. Res. Dev. 6: 482-487 https://doi.org/10.1021/op020028q
  18. Harshad, R. V. and R. H. Mohan. 2003. Biotransformation of (L)-citronellal to (L)-citronellol by free and immobilized Rhodotorula minuta. Electr. J. Biotechnol. 6: 90-103
  19. Hawari, J., A. Halasz, S. Beaudet, L. Paquet, G. Ampleman, and S. Thiboutot. 1999. Biotransformation of 2,4,6-trinitrotoluene with Phanerochaete chrysosporium in agitated cultures at pH 4.5. Appl. Environ. Microbiol. 65: 2977-2986
  20. He, A. and J. P. Rosazza. 2003. Microbial transformations of Snaproxen by Aspergillus niger ATCC 9142. Pharmazie 58: 420-422
  21. Henderson, A. L., T. C. Schmitt, T. M. Heinze, and C. E. Cerniglia. 1997. Reduction of malachite green to leucomalachite green by intestinal bacteria. Appl. Environ. Microbiol. 63: 4099-4101
  22. Ibrahim, A. R., A. M. Galal, M. S. Ahmed, and G. S. Mossa. 2003. O-Demethylation and sulfation of 7-methoxylated flavanones by Cunninghamella elegans. Chem. Pharm. Bull. 51: 203-206 https://doi.org/10.1248/cpb.51.203
  23. Kreiner, M., G. Braunegg, A. de Raadt, H. Griengl, I. Kopper, M. Petsch, et al. 1996. Stereospecific biohydroxylations of protected carboxylic acids with Cunninghamella blakesleeana. Appl. Environ. Microbiol. 62: 2603-2609
  24. Medeiros, S., M. A. Avery, B. Avery, S. G. F. Leite, A. C. C. Freitas, and J. S. Williamson. 2002. Biotransformation of 10- deoxoartemisinin to its 7$\beta$-hydroxy derivative by Mucor ramannianus. Biotechnol. Lett. 24: 937-941 https://doi.org/10.1023/A:1015516929682
  25. Mitsukura, K., Y. Kondo, T. Yoshida, and T. Nagasawa. 2006. Regioselective hydroxylation of adamantane by Streptomyces griseoplanus cells. Appl. Microbiol. Biotechnol. 71: 502-504 https://doi.org/10.1007/s00253-005-0167-7
  26. Miyazawa, M., K. Takahashi, and H. Araki. 2006. Biotransformation of daidzein ditiglate by microorganisms. Nat. Prod. Res. 20: 311-315 https://doi.org/10.1080/14786410500160959
  27. Moody, J. D., D. Zhang, T. M. Heinze, and C. E. Cerniglia. 2000. Transformation of amoxapine by Cunninghamella elegans. Appl. Environ. Microbiol. 66: 3646-3649 https://doi.org/10.1128/AEM.66.8.3646-3649.2000
  28. Pairet, M. and G. Engelhardt. 1996. Differential inhibition of COX-1 and COX-2 in vitro and pharmacological profile in vivo of NSAIDs, pp. 103-119 In J. Vane, J. Botting, and R. Botting (eds), Improved Non-steroid Anti-inflammatory Drugs: COX-2 Enzyme Inhibitors. Kluwer Academic Publishers, London
  29. Parshikov, I. A., J. P. Freeman, A. J. Williams, J. D. Moody, and J. B. Sutherland. 1999. Biotransformation of N-acetylphenothiazine by fungi. Appl. Microbiol. Biotechnol. 52: 553-557 https://doi.org/10.1007/s002530051559
  30. Parshikov, I. A., K. M. Muraleedharan, M. A. Avery, and J. S. Williamson. 2004. Transformation of artemisinin by Cunninghamella elegans. Appl. Microbiol. Biotechnol. 64: 782-786 https://doi.org/10.1007/s00253-003-1524-z