Skip to main content
SpringerLink
Log in

Exogenous shikimic acid stimulates rapamycin biosynthesis inStreptomyces hygroscopicus

  • Papers
  • Published:
Folia Microbiologica Aims and scope Submit manuscript

Abstract

A chemically defined medium was developed which satisfies the nutritional needs of theStreptomyces hygroscopicus strain producing the immunosuppressant rapamycin. More than a doubling of rapamycin biosynthesis was observed on addition of 57 mmol/L of exogenous shikimate. The previously observed inhibition of the synthesis by phenylalanine was not reversed by shikimate.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Byrne K., Shafee A., Nielsen J.B., Arison B., Monaghan R.L., Kaplan L.: The biosynthesis and enzymology of an immunosuppressant, immunomycin, produced byStreptomyces hygroscopicus var.ascomyceticus.Dev. Ind. Microbiol.32, 29–45 (1993).

    Google Scholar 

  • Cheng Y.R., Hauck L., Demain A.L.: Phosphate, ammonium, magnesium and iron nutrition ofStreptomyces hygroscopicus with respect to rapamycin biosynthesis.J. Ind. Microbiol.14, 424–427 (1995a).

    Article  PubMed  CAS  Google Scholar 

  • Cheng Y.R., Fang A., Demain A.L.: Effect of amino acids on rapamycin biosynthesis byStreptomyces hygroscopicus.Appl. Microbiol. Biotechnol.43, 1096–1098 (1995b).

    Article  PubMed  CAS  Google Scholar 

  • Findlay J.A., Radics L.: On the chemistry and high field nuclear magnetic resonance spectroscopy of rapamycin.Can. J. Chem.58, 579–590 (1980).

    Article  CAS  Google Scholar 

  • Floss H.G., Cho H., Casati R., Reynolds K.A., Kennedy E., Moore B.S., Belae J.M., Mocek V.M., Poralla K.: Diversions of the shikimate pathway—The biosynthesis of cyclohexane-carboxylic acid, pp. 77–88, in:Secondary-Metabolite Biosynthesis and Metabolism (R.J. Petroski and S.P. McCormick, Eds). Plenum, New York 1992.

    Google Scholar 

  • Hatanaka H., Kino T., Miyata S., Imunara N., Kuroda A., Goto T., Tanaka H., Okuhara M.: FR-900520 and FR-900523, novel immunosuppressants isolated fromStreptomyces. 2. Fermentation, isolation and physico-chemical and biological characteristics.J. Antibiot.41, 1592–1601 (1987).

    Google Scholar 

  • Kino T., Hatanaka H., Hashimoto M., Nishiyama M., Goto T., Okuhara M., Kohsaka M., Aoki H., Imanaka H.: FK-506, a novel immunosuppressant isolated from aStreptomyces. 1. Fermentation, isolation, and physico-chemical and biological characteristics.J. Antibiot.40, 1249–1255 (1987).

    PubMed  CAS  Google Scholar 

  • Kojima I., Cheng Y.R., Mohan V., Demain A.L.: Carbon source nutrition of rapamycin biosynthesis inStreptomyces hygroscopicus.J. Ind. Microbiol.14, 436–439 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Morris R.E.: Rapamycins: antifungal, antitumor, antiproliferative, and immunosuppressive macrolides.Transpl. Rev.16, 39–87 (1992).

    Article  Google Scholar 

  • Paiva N.L., Demain A.L., Roberts M.F.: Incorporation of acetate, propionate, and methionine into rapamycin byStreptomyces hygroscopicus.J. Nat. Prod.54, 167–177 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Paiva N.L., Roberts M.F., Demain A.L.: The cyclohexane moiety of rapamycin derived from shikimic acid inStreptomyces hygroscopicus.J. Ind. Microbiol.12, 423–428 (1993).

    Article  CAS  Google Scholar 

  • Sehgal S.N., Molnar-Kimber K., Ocain T.D., Weichman B.M.: Rapamycin: a novel immunosuppressive macrolide.Med. Res. Rev.14, 1–22 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Tanaka H., Kuroda A., Marusawa H., Hatanaka H., Kino T., Goto M., Hashimoto M., Taga S.T.: Structure of FK506: a novel immunosuppressant isolated fromStreptomyces.J. Amer. Chem. Soc.109, 5031–5033 (1987).

    Article  CAS  Google Scholar 

  • Vezina C., Kudelski A., Sehgal S.N.: Rapamycin (AY-22 989) a new antifungal antibiotic. 1. Taxonomy of the producing streptomycete and isolation of the active principle.J. Antibiot.28, 721–726 (1975).

    PubMed  CAS  Google Scholar 

  • Vining L.C.: Antibiotic biosynthesis.Biotech. Adv.3, 171–194 (1985).

    Article  CAS  Google Scholar 

  • Wallace K.K., Reynolds K.A., Koch K., McArthur H.A.I., Brown M.S., Wax R.G., Moore B.S.: Biosynthetic studies of ascomycin (FK520): formation of the (1R, 3R, 4R)-3,4-dihydroxycyclohexane carboxylic acid-derived moiety.J. Amer. Chem. Soc.116, 11600–11601 (1994).

    Article  CAS  Google Scholar 

  • Werner R.G.: Secondary metabolites with antibiotic activity from the primary metabolism of aromatic amino acids.Prog. Clin. Biochem. Med.1, 47–115 (1984).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Fermentation Microbiology Laboratory, Massachusetts Institute of Technology, 02139, Cambridge, MA, USA

    A. Fang & A. L. Demain

Authors
  1. A. Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. L. Demain
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Dedicated to Dr. J. Spížek on the occasion of his 60th birthday

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fang, A., Demain, A.L. Exogenous shikimic acid stimulates rapamycin biosynthesis inStreptomyces hygroscopicus . Folia Microbiol 40, 607–610 (1995). https://doi.org/10.1007/BF02818516

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02818516

Keywords

Search

Navigation