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Production of ‘hybrid’ antibiotics by genetic engineering

Nature volume 314, pages 642–644 (1985)Cite this article

Abstract

The recent development of molecular cloning systems in Streptomyces1–4 has made possible the isolation of biosynthetic genes for some of the many antibiotics produced by members of this important genus of bacteria5–10. Such clones can now be used to test the idea that novel antibiotics could arise through the transfer of biosynthetic genes between streptomycetes producing different antibiotics11. The likelihood of a ‘hybrid’ compound being produced must depend on the substrate specificities of the biosynthetic enzymes, about which little is known. In attempts to demonstrate hybrid antibiotic production, we therefore began with strains producing different members of the same chemical class of compounds in order to maximize the chance of success. Here we report the production of novel compounds by gene transfer between strains producing the isochromanequinone antibiotics actinorhodin12, granaticin13 and medermycin14. These experiments were made possible by the recent cloning of the whole set of genes for the biosynthetic pathway of actinorhodin from Streptomyces coelicolor A3(2) (ref. 8). We believe that this represents the first report of the production of hybrid antibiotics by genetic engineering.

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References

  1. Bibb, M. J., Schottel, J. L. & Cohen, S. N. Nature 284, 526–531 (1980).

    Article  ADS  CAS  Google Scholar 

  2. Suarez, J. E. & Chater, K. F. Nature 286, 527–529 (1980).

    Article  ADS  CAS  Google Scholar 

  3. Thompson, C. J., Ward, J. M. & Hopwood, D. A. Nature 286, 525–527 (1980).

    Article  ADS  CAS  Google Scholar 

  4. Bibb, M. J., Chater, K. F. & Hopwood, D. A. in Experimental Manipulation of Gene Expression (ed. Inouye, M.) 53–82 (Academic, New York, 1983).

    Book  Google Scholar 

  5. Feitelson, J. S. & Hopwood, D. A. Molec. gen. Genet. 190, 394–398 (1983).

    Article  CAS  Google Scholar 

  6. Gil, J. A. & Hopwood, D. A. Gene 25, 119–132 (1983).

    Article  CAS  Google Scholar 

  7. Chater, K. F. & Bruton, C. J. Gene 26, 67–78 (1983).

    Article  CAS  Google Scholar 

  8. Malpartida, F. & Hopwood, D. A. Nature 309, 462–464 (1984).

    Article  ADS  CAS  Google Scholar 

  9. Bailey, C. R., Butler, M. J., Normansell, N. D., Rowlands, R. T. & Winstanley, D. J. Bio/ Technology 2, 808–811 (1984).

    CAS  Google Scholar 

  10. Jones, G. H. & Hopwood, D. A. J. biol. Chem. 259, 14151–14157 (1984).

    CAS  PubMed  Google Scholar 

  11. Hopwood, D. A. in Beta-lactam Antibiotics (eds Salton, M. R. J. & Shockmann, G. D.) 585–598 (Academic, New York, 1981).

    Google Scholar 

  12. Brockmann, H., Zeeck, A., van der Merve, K. & Müller, W. Justus Liebigs Annln Chem. 698, 3575–3579 (1966).

    Article  Google Scholar 

  13. Carbaz, R. et al. Helv. chim. Acta 40, 1262–1269 (1957).

    Article  Google Scholar 

  14. Ogura, H. & Furuhata, K. Abstr. 9th int. Congr. Heterocyclic Chem., 114 (1983).

  15. Lydiate, D. J., Malpartida, F. & Hopwood, D. A. Gene (in the press).

  16. Thompson, C. J., Ward, J. M. & Hopwood, D. A. J. Bact. 151, 668–677 (1982).

    CAS  PubMed  Google Scholar 

  17. Pyrek, J. S.-P., Achmatowicz, O. & Zamojski, A. Tetrahedron 33, 673–680 (1977).

    Article  CAS  Google Scholar 

  18. Ihn, W., Schlegel, B., Fleck, W. F. & Sedmera, P. J. Antibiot., Tokyo 33, 1457–1461 (1980).

    Article  CAS  Google Scholar 

  19. Mazières, N., Peyré, M. & Pénasse, L. J. Antibiot., Tokyo 34, 544–550 (1981).

    Article  Google Scholar 

  20. Traxler, P., Schupp, T., Fuhrer, H. & Richter, W. J. J. Antibiot., Tokyo 34, 971–979 (1981).

    Article  CAS  Google Scholar 

  21. Hopwood, D. A. in Biochemistry and Genetic Regulation of Commercially Important Antibiotics (ed. Vining, L. C.) 1–23 (Addison-Wesley, Reading, Massachusetts, 1983).

    Google Scholar 

  22. Rudd, B. A. M. & Hopwood, D. A. J. gen. Microbiol. 114, 35–43 (1979).

    Article  CAS  Google Scholar 

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Author notes

  1. B. A. M. Rudd

    Present address: Glaxo Group Research, Greenford, Middlesex, UB6 0HE, UK

Authors and Affiliations

  1. John Innes Institute, Colney Lane, Norwich, NR4 7UH, UK

    D. A. Hopwood, F. Malpartida & H. M. Kieser

  2. School of Pharmaceutical Sciences, Kitasato University and The Kitasato Institute, Tokyo, 108, Japan

    H. Ikeda & S. Ōmura

  3. Department of Chemistry, Ohio State University, Columbus, Ohio, 43210, USA

    J. Duncan, I. Fujii & H. G. Floss

  4. Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana, 47907, USA

    B. A. M. Rudd

Authors
  1. D. A. Hopwood
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  4. H. Ikeda
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  5. J. Duncan
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  6. I. Fujii
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  7. B. A. M. Rudd
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  8. H. G. Floss
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  9. S. Ōmura
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Hopwood, D., Malpartida, F., Kieser, H. et al. Production of ‘hybrid’ antibiotics by genetic engineering. Nature 314, 642–644 (1985). https://doi.org/10.1038/314642a0

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