Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지

Lipase Activity and Tacrolimus Production in Streptomyces clavuligerus CKD 1119 Mutant Strains

  • Kim, Hyung-Soo (Department of Biotechnology, School of Life Science and Biotechnology, Korea University) ;
  • Park, Young-In (Department of Biotechnology, School of Life Science and Biotechnology, Korea University)
  • Published : 2007.10.30
Download PDF
⟨ Previous Next ⟩

Abstract

The effect of carbon sources on tacrolimus production by a mutant strain of Streptomyces clavuligerus CKD 1119, an isolate from soil, was examined. Among the carbohydrates and oils tested in this work, a mixed carbon source of soluble starch and com oil was the best. An analysis of the culture kinetics also showed that, in contrast to the carbohydrates, the com oil was consumed later in the antibiotic production phase, implying that the oil substrate was the principal carbon source for the biosynthesis of tacrolimus, and this was directly proven by experiments using $^{14}C$-glucose and $^{14}C$-oleate substrates. Furthermore, com oil induced the formation of lipase by the mutant strain, whereas the addition of glucose significantly repressed lipase activity. The lipase activity exhibited by the FK-506-overproducing mutants was also observed to be directly proportional to their tacrolimus yield, indicating that a high lipase activity is itself a crucial factor for tacrolimus production. A feasibility study with a 200-1 pilot-scale fermentor and the best strain (Tc-XII-15322) identified in this work revealed a high volumetric and specific productivity of about 495 mg/l and 0.34 mg/mg dry mycelium, respectively.

Keywords

References

  1. Aharonowitz, Y. and A. L. Demain. 1978. Carbon catabolite regulation of cephalosporin production in Streptomyces clavuligerus. Antimicrob. Agents Chemother. 14: 159-164 https://doi.org/10.1128/AAC.14.2.159
  2. Ahn, J. O., H. W. Jang, H. W. Lee, E. S. Choi, S. J. Haam, T. K. Oh, and J. K. Jung. 2003. Overexpression of thermoalkalophilic lipase from Bacillus stearothermophilus L1 in Saccharomyces cerevisiae. J. Microbiol. Biotechnol. 13: 451-456
  3. Akashi, T., T. Nefuji, M. Yoshida, and J. Hosoda. 1996. Quantitative determination of tautomeric FK-506 by reversedphase liquid chromatography. J. Pharmaceut. Biomed. Anal. 14: 339-346 https://doi.org/10.1016/0731-7085(95)01605-8
  4. Berk, P. D. 1996. How do long-chain free fatty acids cross cell membranes? Proc. Soc. Exp. Biol. Med. 212: 1-4
  5. Cavanagh, M. F., A. P. Ison, M. D. Lilly, and S. W. Carleysmith. 1994. The utilization of lipids during Streptomycete fermentations. IChemE Res. Event, Two-Day Symp. Institute of Chemical Engineering, Rugby, UK. 1: 226-228
  6. Cheigh, C.-I., S.-J. Lee, Y.-R. Pyun, D.-J. An, Y.-S. Hwang, Y. Chung, and H. Park. 2005. The effect of carbon sources on nisin z biosynthesis in Lactococcus lactis subsp. lactis A164. J. Microbiol. Biotechnol. 15: 1152-1157
  7. Dumont, F. J., M. R. Melino, M. J. Staruch, S. L. Koprak, P. A. Fischer, and N. H. Sigal. 1990. The immunosuppressive macrolides FK506 and rapamycin act as reciprocal antagonists in murine T cells. J. Immunol. 144: 1418-1424
  8. Harwood, J. 1989. The versatility of lipase for industrial uses. Trends Biochem. Sci. 14: 125-126 https://doi.org/10.1016/0968-0004(89)90140-0
  9. Hatanaka, H., T. Kino, M. Asano. T. Goto, H. Tanaka, and M. Okuhara. 1988. FK506 related compounds produced by Streptomyces tsukubaensis. No. 9993. J. Antibiot. 42: 620-622
  10. Hopwood, D. A. 1997. Genetic contributions to understanding polyketide synthases. Chem. Rev. 97: 2485-2497
  11. Huge-Jensen, B., D. R. Galluzzo, and R. G. Jensen. 1987. Partial purification and characterization of free and immobilized lipases from Mucor miehei. Lipids 22: 559-565 https://doi.org/10.1007/BF02537281
  12. Kim, J. C., S. W. Kang, J. S. Lim, Y. S. Song, and S. W. Kim. 2006. Stimulation of cephalosporin C production by Acremonium chrysogenum M35 with fatty acids. J. Microbiol. Biotechnol. 16: 1120-1124
  13. Kino, T., H. Hatanaka, S. Miyata, N. Inamura, M. Nishiyama, T. Yajima, T. Goto, M. Okuhara, M. Kohsaka, and H. Aoki. 1987. FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, physico-chemical and biological characterization. J. Antibiot. 40: 1249-1255 https://doi.org/10.7164/antibiotics.40.1249
  14. Kino, T., T. Hatanaka, S. Miyata, N. Inamura, N. Nishiyama, T. Yajima, T. Goto, M. Okuhara, M. Kohsaka, H. Aoki, and T. Ochiai. 1987. FK-506: A novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J. Antibiot. 40: 1256-1265 https://doi.org/10.7164/antibiotics.40.1256
  15. Kosugi, Y. and H. Suzuki. 1973. Fixation of cell-bound lipase and properties of the fixed lipase as an immobilized enzyme. J. Ferment. Technol. 51: 895-903
  16. Large, K. P., N. Mirjalili, M. Osborne, L. M. Peacock, V. Zormpaidis, M. Walsh, M. E. Cavanagh, P. F. Leadlay, and A. P. Ison. 1999. Lipase activity in Streptomycetes. Enz. Microb. Technol. 25: 569-575 https://doi.org/10.1016/S0141-0229(99)00080-0
  17. Longo, M. A. and D. Combes. 1995. A novel chemoenzymatic glycosylation strategy: Application to lysozyme modification. FEBS Lett. 375: 63-66 https://doi.org/10.1016/0014-5793(95)01174-D
  18. Macrae, A. R. and R. C. Hammond. 1988. Present and future applications of lipases. Biotechnol. Genet. Eng. Rev. 3: 193-217
  19. Macris, J. B., E. Kourentzi, and D. G. Hatzinikolaou. 1996. Studies on localization and regulation of lipase production by Aspergillus niger. Process Biochem. 31: 807-812 https://doi.org/10.1016/S0032-9592(96)00037-4
  20. Omura, S., Y. Tanaka, C. Kitao, H. Tanaka, and Y. Iwai. 1980. Stimulation of leucomycin production by magnesium phosphate and its relevance to nitrogen catabolite regulation. Antimicrob. Agents Chemother. 18: 691-695 https://doi.org/10.1128/AAC.18.5.691
  21. Park, Y. S., I. Momose, K. Tsunoda, and M. Okabe. 1994. Enhancement of cephamycin C production using soybean oil as the sole carbon source. Appl. Microbiol. Biotechnol. 40: 773-779 https://doi.org/10.1007/BF00173973
  22. Reynolds, K. A. and A. L. Demain. 1997. Rapamycin, FK506, and ascomycin-related compounds, Chapter 17, pp. 497-520. In William Strohl (ed.), Biotechnology of Antibiotics. Marcel Dekker, New York
  23. Sawada, S., G. Suzuki, Y. Kawase, and F. Takaku. 1987. Novel immunosuppressive agent, FK506. In vitro effects on the cloned T cell activation. J. Immunol. 139: 1797-1803
  24. Shafiee, A. and H. Motadedi. 1997. Chemical and biological characterization of two FK-506 analogs produced by targeted gene disruption in Streptomyces sp. MA6548. J. Antibiot. 50: 418-423 https://doi.org/10.7164/antibiotics.50.418
  25. Stuer, W., K. E. Jae, and U. K. Winkler. 1986. Purification of extracellular lipase from Pseudomonas aeruginosa. J. Bacteriol. 168: 1070-1074 https://doi.org/10.1128/jb.168.3.1070-1074.1986
  26. Sugiura, T., T. Ota, and Y. Minoda. 1975. Effects of fatty acids, lipase activator, phospholipids and related substances on the lipase production by Candida paralipolytica. Agric. Biol. Chem. 39: 1689-1694 https://doi.org/10.1271/bbb1961.39.1689
  27. Tsujisaka, Y., M. Iwai, J. Fukumoto, and Y. Okamoto. 1973. Induced formation of lipase by Geotrichum candidum link. Agric. Biol. Chem. 37: 837-842 https://doi.org/10.1271/bbb1961.37.837
  28. Watanabe, N., Y. Ota, Y. Minoda, and K. Yamada. 1977. Isolation and identification of alkaline lipase producing microorganisms, cultural conditions and some properties of crude enzymes. Agric. Biol. Chem. 41: 1353-1358 https://doi.org/10.1271/bbb1961.41.1353