Enhanced Prodiginines Production in Streptomyces coelicolor M511 by Stress of Acidic pH Shock

산성 pH 충격 스트레스에 의한 스트랩토마이세스 시에리컬러 M511의 프로디지닌 생산 증대

  • Mo, Sang-Joon (Department of Chemistry and Nano Science, Ewha Womans University)
  • 모상준 (이화여자대학교 화학나노과학)
  • Received : 2010.05.10
  • Accepted : 2010.07.08
  • Published : 2010.09.28

Abstract

Undecylprodiginine and streptorubin B are red-pigmented antibiotics produced by Streptomyces coelicolor A3(2). In this study, we investigated the correlation between productivity of these red-pigmented antibiotics and stress of pH shock. Biosynthesis of these red-pigmented antibiotics is enhanced at acidic pH shock on solid R2YE medium. The optimal pH shock is pH 4 which led to 1.6 fold and two-fold increase in the production of undecylprodiginine and streptorubin B as compared with control, respectively. In addition, the extract of pH 4 shocked cells exhibited a remarkable activity against Trichophyton mentagrophytes. However, neutral and basic pH shock did not give raise to promote a production of these red-pigmented antibiotics as well as antifungal activity. Thus, although the acidic pH shock is simple and easy method, it should be extremely effective approach to enhance a productivity of these red-pigmented antibiotics and other secondary metabolites.

운데실프로지닌과 스트래토루빈 B는 S. coelicolor가 생산하는 붉은색 항생물질이다. 이번 연구에서 이들 붉은색 항생제의 생산성과 pH shock 스트레스와의 상관관계를 연구 하였다. 운데실프로디지닌과 스트랩토루빈 B의 생합성은 고체 R2YE 배지에서 산성 pH shock에 의해 증가되었다. 최적 pH shock은 pH 4로 비교군과 비교하여 각각 1.6배 및 2배 운데실프로디진과 스트랩토루빈 B의 생산성이 증가되었다. 게다가, 산성 pH 4의 세포 추출물은 T. mentagrophytes 에 대한 주목할만한 저항 활성을 나타내었다. 그러나, 중성 및 염기성 pH shock에서는 이들 항생제의 생산성뿐만 아니라 항진균 활성 증가가 일어나지 않았다. 그러므로, 비록 산성 pH shock이 간단하고 쉬운 방법이지만, 이들 붉은색 항생물질과 다른 이차대사산물의 생산성 향상에는 매우 효과적인 접근방법일 것이다.

Keywords

References

  1. Anderson, G., D. A. Ritchie, C. Cappellano, R. H. Cool, N. M. Ivanova, A. S. Huddleston, C. S. Flaxman, V. Kristufek, and A. Lounes. 1993. Physiology and genetics of antibiotic production and resistance. Res. Microbiol. 144: 665-672. https://doi.org/10.1016/0923-2508(93)90072-A
  2. Bentley, S. D., K .F. Chater, A. M. Cerdeno-Tarraga, G. L. Challis, N. R. Thomson, K. D. James, D. E. Harris, M. A. Quail, H. Kieser, D. Harper, A. Bateman, S. Brown, G. Chandra, C. W. Chen, M. Collins, A. Cronin, A. Fraser, A. Goble, J. Hidalgo, T. Hornsby, S. Howarth, C. H. Huang, T. Kieser, L. Larke, L. Murphy, K. Oliver, S. O'Neil, E. Rabbinowitsch, M. A. Rajandream, K. Rutherford, S. Rutter, K. Seeger, D. Saunders, S. Sharp, R. Squares, S. Squares, K. Taylor, T. Warren, A. Wietzorrek, J. Woodward, B. G. Barrell, J. Parkhill, and D. A. Hopwood. 2002. Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 417: 141-147. https://doi.org/10.1038/417141a
  3. Beppu, T. 1995. Signal transduction and secondary metabolism: Prospects for controlling productivity. Trends Biotechnol. 13: 264-269. https://doi.org/10.1016/S0167-7799(00)88961-1
  4. Bruheim, P., H. Sletta, M. J. Bibb, J. White, and D. W. Levine. 2002. High-yield actinorhodin production in fedbatch culture by a Streptomyces lividance strain overexpressing the pathway-specific activator gene actII-ORF4. J. Ind. Microbiol. Biotech. 28: 103-111.
  5. Cerdeno, A. M., M. J. Bibb, and G. L. Challis. 2001. Analysis of the prodiginine biosynthesis gene cluster of Streptomyces coelicolor A3(2): new mechanisms for chain initiation and termination in modular multienzymes. Chem. Biol. 8: 817-829. https://doi.org/10.1016/S1074-5521(01)00054-0
  6. Chater, K. F. 1992. Genetic regulation of secondary metabolic pathway in Streptomyces. Ciba Found. Symp. 171: 144-162.
  7. Chater, J. K. 1998. Talking in genetic scalpel to the Streptomyces colony. Microbiology 144: 1465-1478. https://doi.org/10.1099/00221287-144-6-1465
  8. Gerber, N., A. McInnes, D. Smith, J. Walter, J. Wright, and L. Vining. 1978. Biosynthesis of progidinines. 13C assignments and enrichment patter in nonyl-, cyclononyl-, methylcyclodecyl-, and butylcycloheptylproginine produced by actimin nomycete cultures supplemented with $^{13}C$-labeled acetate and $^{15}N$--labeled nitrate. Can. J. Chem. 56: 1155–1163. https://doi.org/10.1139/v78-194
  9. Hayes, A., G. Hobbs, C. P. Smith, S. G. Oliver, and P. R. Butler. 1997. Environmental signals riggering methylenomycin production by Streptomyces coelicolor A3(2). J. Bacteriol. 179: 5511-5.
  10. Haynes, S. W., P. K. Sydor, A. E. Stanley, L. Song, and G. L. Challis. 2008. Role and substrate specificity of the Streptomyces coelicolor RedH enzyme in undecylprodiginine biosynthesis. Chem. Commun. 16: 1865-1867.
  11. Hopwood, D. A. 1987. Towards an understanding of gene switching in Streptomyces, the basis: of sporulation and antibiotic production. Proc. R. Soc. Lond. Series B 23: 2257-2269.
  12. Horinouchi, S. 2003. AfsR as an integrator of signals that are sensed by multiple serine/threonine kinases in Streptomyces coelicolor A3(2). J. Ind. Microbiol. Biotechnol. 30: 462-467. https://doi.org/10.1007/s10295-003-0063-z
  13. Horinouchi, S. and T. Beppu. 1992. Regulation of secondary metabolism and cell differentiation in Streptomyces: A-factor as a microbial hormone and the AfsR protein as a component of a two-component regulatory system. Gene 115: 167-172. https://doi.org/10.1016/0378-1119(92)90555-4
  14. Hu, H., Q. Zhang, and K. Ochi. 2002. Activation of antibiotic biosynthesis by specified mutations in the rpoB gene (encoding the RNA polymerase b subunit) of Streptomyces lividans. J. Bacteriol. 184: 3984-3991. https://doi.org/10.1128/JB.184.14.3984-3991.2002
  15. Hung, J. L., C.-J Lih, K.-H Pan, and S. N. Cohen. 2001. Grobal analysis of growth phase responsive gene expression and regulation of antibiotic biosynthesis pathways in Sytreptomyces coelicolor using DNA microarrays. Genes Dev. 15: 3183-3192. https://doi.org/10.1101/gad.943401
  16. Hur, Y. A., S. S. Choi, Y. K. Chang, S. K. Hong, and E. S. Kim. 2007. Solid medium pH-dependent antifungal activity of Streptomyces sp. producing an immunosuppressant, Tautomycetin. Kor. J. Microbiol. Biotechnol. 35: 26-29.
  17. Keiser, T., M. J. Bibb, M. J. Buttner, K. F. Chater, and D. A. Hopwood. 2000. Practical Streptomyces Genetics. The John Innes Foundation, Norwich, United Kingdom.
  18. Kim, C. J., Y. K. Chang, and G. T. Chun. 2000. Enhancement of kasugamycin production by pH shock in batch cultures of Streptomyces kasugaensis. Biotechnol. Prog. 16: 548-552. https://doi.org/10.1021/bp000038f
  19. Kim, Y. J., J. Y. Song, M. H. Moon, C. P. Smith, S. K. Hong, and Y. K. Chang. 2007. pH shock induces overexpression of regulatory and biosynthetic genes for actinorhodin productionin Streptomyces coelicolor A3(2). Appl. Microbiol. Biotechnol. 5: 1119-1130.
  20. Kim, Y. J., M. H. Moon, J. Y. Song, C. P. Smith, S. K. Hong, and Y. K. Chang. 2008. Acidic pH shock induces the expressions of a wide range of stress-response genes. BMC Genomics 9: 604. https://doi.org/10.1186/1471-2164-9-604
  21. Nguyen, M., R. C. Marcellus, A. Roulston, M. Watson, L. Serfass , M. S. R. Murthy, D. Goulet, J. Viallet, L. Belec, X. Billot, S. Acoca, E. Purisima, L. Wiegmans, L. Cluse, R. W. Johnstone, P. Beauparlant, and G. C. Shore. 2007. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc. Natl. Acad .Sci. USA 104: 19512-19517. https://doi.org/10.1073/pnas.0709443104
  22. Sevcikova, B. and J. Kormanec. 2004. Differential production of two antibiotics of Streptomyces coelicolor A3(2), actinorhodin and undecylprodigiosin, upon salt stress conditions. Arch. Microbiol. 181: 384-389. https://doi.org/10.1007/s00203-004-0669-1
  23. Shore, G. C., J. Bajorath, F. L. Stahura, and M. S. R. Murthy. 2003. International Patent application WO 2003015788.
  24. Williams, R. P., J. A. Green, and D. A. Rappo-Port. 1956. Studies on pigmentation of Serratia marcescens. I. Spectral and paper chromatographic properties of prodiginine. J. Bacteriol. 71: 115-120.