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Rapid identification of teleocidins in fermentation broth using HPLC photodiode array and LC/MS methodology

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Journal of Industrial Microbiology

Summary

During the course of screening for inhibitors of phorbol ester binding to protein kinase C, several actinomycete cultures were discovered that produce active metabolites. HPLC coupled to photodiode array and LC/MS techniques were applied to broth extracts to identify the presence of indolactams belonging to the teleocidin family. Various members of this family were rapidly identified from crude broth extracts using a combination of these spectroanalytical procedures. An analytical HPLC system was developed to optimize separation of teleocidin, A and B analogues directly from ethyl acetate extracts of whole broth cultures. This technique allowed us to identify a novel homologue of pendolmycin and demonstrated the utility of photodiode array HPLC coupled with LC/MS as an intial analytical tool in the analyses of these secondary metabolites produced by soil microorganisms.

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References

  1. Blumberg, P.M. 1988. Protein kinase C as the receptor for the phorbol ester tumor promoters: Sixth Rhoads Memorial Award lecture. Cancer Res. 48: 1–8.

    Google Scholar 

  2. Cardellina, J.H., F.-Z. Marner, and R.E. Moore. 1979. Seeweed dermatitis: structure of lyngbyatoxin A. Science 204: 193–195.

    Google Scholar 

  3. Dunphy, W.G., R.J. Kochenburger, M. Castagna, and P.M. Blumberg. 1981. Kinetics and subcellular localization of specific [3H]phorbol 12, 13-dibutyrate binding by mouse brain. Cancer Res. 41: 2640–2647.

    Google Scholar 

  4. Fujiki, H. and T. Sugimura. 1983. New potent tumour promoters: teleocidin, lyngbyatoxin A and aplysiatoxin. Cancer Surv 2: 539–556.

    Google Scholar 

  5. Hitotsuyanagi, Y., H. Fujiki, M. Suganuma, N. Aimi, S. Sakai, Y. Endo, K. Shudo, and T. Sugimura. 1984. Isolation and structure elucidation of teleocidin B-1, B-2, B-3, and B-4. Chem. Pharm. Bull. 32: 4233–4236.

    Google Scholar 

  6. Itai, A., Y. Kato, N. Tomioka, Y. Iitaka, Y. Endo, M. Hasegawa, K. Shudo, H. Fujiki, and S. Sakai. 1988. A receptor model for tumor promoters: rational superposition of teleocidins and phorbol esters. Proc. Natl. Acad. Sci. USA 85: 3688–3692.

    Google Scholar 

  7. Mierzwa, R., J. Marquez, M. Patel and R. Cooper. 1989. HPLC Detection Methods for Microbial Products in Fermentation Broth. In: Natural Products Isolation, Chapter 2, Ed. (G.W. Wagman and R. Cooper (eds.) Elsevier, Amsterdam.

    Google Scholar 

  8. Nishizuka, Y. 1986. Studies and perspectives of protein kinase C. Science 233: 305–312.

    Google Scholar 

  9. Nishizuka, Y. 1988. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature 334: 661–665.

    Google Scholar 

  10. Sakai, S., N. Aimi, K. Yamaguchi, Y. Hitotsuyanagi, C. Watanabe, K. Yokose, Y. Koyama, K. Shudo, and A. Itai. 1984. Elucidation of the structure of olivoretin A and D (teleocidin B). Chem. Pharm. Bull. 32: 354–357.

    Google Scholar 

  11. Sakai, S., Y. Hitotsuyanagi, N. Aimi, H. Fujiki, M. Suganuma, T. Sugimura, Y. Endo, and K. Shudo. 1986. Absolute configuration of lyngbyatoxin A (teleocidin A-1) and teleocidin A-2. Tetrahedron Lett. 27: 5219–5220.

    Google Scholar 

  12. Sakai, S., Y. Hitotsuyanagi, K. Yamaguchi, N. Aimi, K. Ogata, T. Kuramochi, H. Seki, R. Hara, H. Fujiki, M. Suganuma, T. Sugimura, Y. Endo, K. Shudo, and Y. Koyama. 1986. The structures of additional teleocidin class tumor promoters. Chem. Pharm. Bull. 34: 4883–4886.

    Google Scholar 

  13. Sun H.H., White, C.B., Sedlock, D.M., Dedinas, J. and R. Cooper. 1991. Methylpendolmycin, a novel indolactam from aNocardiopsis sp. J. Nat. Prod., 54: 1440–1443.

    Google Scholar 

  14. Takashima, M. and H. Sakai. 1960. A new toxic substance, teleocidin, produced byStreptomyces. I. Production, isolation and chemical studies. Bull. Agr. Chem. Soc. Japan 24: 647–651.

    Google Scholar 

  15. Yamashita, T., M. Imoto, K. Isshiki, T. Sawa, H. Naganawa, S. Kurasawa, B.-Q. Zhu, and K. Umezawa. 1988. Isolation of a new indole alkaloid pendolmycin, fromNocardiopsis. J. Nat. Prod. 51: 1184–1187.

    Google Scholar 

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Sedlock, D.M., Sun, H.H., Smith, W.F. et al. Rapid identification of teleocidins in fermentation broth using HPLC photodiode array and LC/MS methodology. Journal of Industrial Microbiology 9, 45–52 (1992). https://doi.org/10.1007/BF01576367

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  • DOI: https://doi.org/10.1007/BF01576367

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