Skip to main content
Log in

Regulation of spiramycin synthesis in Streptomyces ambofaciens: effects of glucose and inorganic phosphate

  • Original Paper
  • Applied Microbial and Cell Physiology
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

The production of the 16-membered macrolide antibiotic, spiramycin, in Streptomyces ambofaciens is inhibited by glucose, 2-deoxyglucose and inorganic phosphate. The role of intracellular ATP content and phosphorylated metabolites as common regulating signals of both glucose and phosphate inhibitory effects is discussed. Two enzymatic targets of the effect of phosphate on spiramycin biosynthesis were studied. Valine dehydrogenase, the first enzyme of valine catabolism (supplier of aglycone spiramycin precursors), and alkaline phosphatase, which cleaves phosphorylated intermediates, were repressed in the presence of excess phosphate.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Burton K (1956) A study of the conditions and mechanisms of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62: 315–323

    CAS  Google Scholar 

  • Demain AL, Inamine E (1970) Biochemistry and regulation of streptomycin and mannosidostreptomycinase (α-D-mannosidase) formation. Bacteriol Rev 34: 1–5

    CAS  Google Scholar 

  • Dietz GW, Heppel A (1971) 2-Deoxyglucose and 2-deoxyglucose 6-phosphate. J Biol Chem 246: 2881–2884

    CAS  Google Scholar 

  • Dotzalf JE, Metzgze LS, Foglesong MA (1984) Incorporation of aminoacid-derived carbon into tylactone by Streptomyces fradiae GS14. Antimicrob Agents Chemother 25: 216–220

    Google Scholar 

  • Drew SW, Demain AL (1977) Effect of primary metabolites on secondary metabolism. Annu Rev Microbiol 31: 343–349

    Article  CAS  Google Scholar 

  • Griswold BC, Humoller FL, Mac Intyre AR (1951) Inorganic phosphate and phosphate ester in tissue extracts. Anal Chem 23: 192–194

    Article  CAS  Google Scholar 

  • Hanson RS, Philips JA (1981) Chemical composition. In: Gehardt P, et al (eds) Manual of methods for general bacteriology. American Society for Microbiology, Washington, DC, pp 328–331

    Google Scholar 

  • Isaacson DM, Kirschbaum J (1986) Assays of antimicrobial substances. In: Demain AL, Solomon NA (eds) Manual of industrial microbiology and biotechnology. American Society for Microbiology, Washington, DC, pp 410–435

    Google Scholar 

  • Jakubczak E, Leclerc H (1980) Mesure de l’ATP bactérien par bioluminescence: étude critique des méthodes d’extraction. Ann Biol Clin 38: 297–304

    CAS  Google Scholar 

  • Kuzdzal-Savoie S, Lebon F (1971) Extraction of butterfat from liquid or dried milk. Tech Lait 690: 12–13

    Google Scholar 

  • Lebrihi A, Germain P, Lefebvre G (1987) Phosphate repression of cephamycin and clavulanic acid production by Streptomyces clavuligerus. Appl Microbiol Biotechnol 28: 44–51

    Google Scholar 

  • Liras P, Villanueva JR, Martin JF (1977) Sequential expression of macromolecule biosynthesis and candicidin formation in Streptomyces griseus. J Gen Microbiol 102: 269–277

    CAS  Google Scholar 

  • Lowry O, Rosebrough N, Farr A, Randall L (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275

    CAS  Google Scholar 

  • Madry N, Sprinkmeyer D, Pape H (1979) Regulation of tylosine synthesis in Streptomyces: effect of glucose analogs and inorganic phosphate. Eur J Appl Microbiol Biotechnol 7: 365–370

    Article  CAS  Google Scholar 

  • Martin JF (1977) Control of antibiotic synthesis by phosphate. Adv Biochem Eng 6: 105–127

    CAS  Google Scholar 

  • Mertz FP, Doolin LE (1973) The effect of inorganic phosphate on the biosynthesis of vancomycin. Can J Microbiol 19: 263–270

    Article  CAS  Google Scholar 

  • Miller GL (1959) Use of dinitrosalycilic acid reagent for determination of reducing sugars. Anal Chem 31: 426–429

    Article  CAS  Google Scholar 

  • Omura S, Tanaka Y (1986) Biosynthesis of tylosin and its regulation by ammonium and phosphate. In: Kleinkauf H, Dohren HV. Dormaner H, Nesmann G (eds) Regulation of secondary metabolism formation. VCH, Berlin, pp 306–332

    Google Scholar 

  • Omura S, Tanaka Y, Mamada H, Masuma R (1984) Effect of ammonium ion, inorganic phosphate and amino acids on the biosynthesis of protylonolide, a precursor of tylosin aglycone. J Antibiot (Tokyo) 37: 494–502

    CAS  Google Scholar 

  • Payne GF, Wang HY (1988) Phosphate feeding to permit growth while maintaining secondary product synthesis. Appl Microbiol Biotechnol 27: 572–576

    CAS  Google Scholar 

  • Schindelmeiser J, Pape H (1981) Relationship between macrotetrolide production and specific activity of some hydrolases in a high and low producing strain of Streptomyces griseus. Eur J Appl Microbiol Biotechnol 11: 216–221

    Article  CAS  Google Scholar 

  • Schütte H, Hummel W, Tsai H, Kula M-R (1985) L-Leucine dehydrogenase from Bacillus cereus: production, large-scale purification and protein characterization. Appl Microbiol Biotechnol 22: 306–317

    Article  Google Scholar 

  • Vu-Trong K, Bhuwapathanapun S, Gray PP (1980) Metabolic regulation in tylosin-producing Streptomyces fradiae: regulatory role of adenylate nucleotide pool and enzymes involved in biosynthesis of tylonolide precursors. Antimicrob Agents Chemother 17: 519–604

    CAS  Google Scholar 

  • Vu-Trong K, Bhuwapathanapun S, Gray PP (1981) Metabolic regulation in tylosin-producing Streptomyces fradiae: phosphate control of tylosin biosynthesis. Antimicrob Agents Chemother 19: 209–212

    CAS  Google Scholar 

  • Walker MS, Walker JB (1971) Streptomycin biosynthesis. Separation and substrate specificities of phosphatases acting on guanidinodeoxy-scyllo-inositol phosphate and streptomycin-(streptidino) phosphate. J Biol Chem 246: 7034–7039

    CAS  Google Scholar 

  • Weber MJ (1973) Hexose transport in normal and Rous Sarcoma virus-transformed cells. J Biol Chem 248: 2978–2983

    CAS  Google Scholar 

  • Weinberg ED (1974) Secondary metabolism: control by temperature and inorganic phosphate. Dev Ind Microbiol 15: 70–76

    CAS  Google Scholar 

  • Weinberg ED (1978) Secondary metabolism: regulation by phosphate and trace elements. Folia Microbiol 23: 496–501

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lounès, A., Lebrihi, A., Benslimane, C. et al. Regulation of spiramycin synthesis in Streptomyces ambofaciens: effects of glucose and inorganic phosphate. Appl Microbiol Biotechnol 45, 204–211 (1996). https://doi.org/10.1007/s002530050671

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s002530050671

Keywords

Navigation