Biosynthesis of monensins a and b: the role of isoleucine

Abstract

Isoleucine added to the cultivation medium ofStreptomyces cinnamonensis C-10Q-5 induced a relative increase of the production of monensin B at the expense of monensin A.U-14C-Isoleucine was found not to be a specific monensin B precursor. The incorporation of l-13C-2-methylbutyrate into monensins A and B showed the label to be evenly incorporated in both products at carbon atoms originating from C(i) of propionate. In regulatory mutants insensitive to 2-amino-3-cblorobutyrate isoleucine influenced the production of monensins only slightly but strains resistant to 2-aminobutyrate and norleucine decreased their total production by 2—12 % in the presence of isoleucine which was associated with a decrease of monensin A content by 14—52 %. The inhibitory effect of isoleucine on the biosynthesis of valine, a specific precursor of the butyrate unit of monensin A, is discussed.

This is a preview of subscription content, access via your institution.

References

  1. Agtarap A., Chamberlin J. W.: Monensin, a new biologically active compound. IV. Chemistry.Antimicrob. Agents Chemother. 1967, 359 (1968).

    Google Scholar 

  2. Agtarap A., Chamberlin J. W., Pinkerton M., Steinrauf L.: The structure of monensinic acid, a new biologically active compound.J.Amer.Chem.Soc. 89, 5737 (1967).

    Article  CAS  Google Scholar 

  3. Cane D. E., Celmeb W. D., Westley J. W.: Unified stereochemioal model of polyether antibiotic structure and biogenesis.J.Amer.Chem.Soc. 105, 3594 (1983).

    Article  CAS  Google Scholar 

  4. Cane D. E., Liang T.-C, Hasler II.: Polyether biosynthesis. Origin of the oxygen atoms in monensin A.J.Amer.Chem.Soc. 103, 5962 (1981).

    Article  CAS  Google Scholar 

  5. Cane D. E., Liang T.-C, Hasleb H.: Polyether biosynthesis. 2. Origin of the oxygen atoms in monensin A.J.Amer.Chem.Soc. 104, 7274 (1982).

    Article  CAS  Google Scholar 

  6. Day L. E., Chamberlin J. W., Gordek E. Z., Chen S., Goeman M., Hamill R. E., Wess T., Weeks R. E., Stroshane R.: Biosynthesis of monensin.Antimicrob.Agents Chemother. 4, 410 (1973).

    PubMed  CAS  Google Scholar 

  7. Furihata K., Seto H., Ohuchi M., Otake N.: Selective INEPT, a new technique for the13C NMR assignment of methylene carbons with non-equivalent protons, and its application to the analysis of the13C NMR spectrum of monensin.Org.Magn.Reson. 21, 624 (1983).

    Article  CAS  Google Scholar 

  8. Hauest M. E., Hoehn M. M.: Monensin, a new biologically active compound. I. Discovery and isolation.Antimicrob.Agents Chemother. 1967, 349 (1968).

    Google Scholar 

  9. Hessbltine C. W., Benedict R. G., Pbidham F. G.: Useful criteria for species differentiation in the genusStreptomyces.Ann.N.Y.Acad.Sci. 60, 136 (1954).

    Article  Google Scholar 

  10. Lutz W. K., Winkler F. K., Dunitz J. D.: Crystal structure of the antibiotic monensin. Similarities and differences between the free acid and metal complex.Helv.Chim.Acta 54, 1103 (1971).

    PubMed  Article  CAS  Google Scholar 

  11. Ovchiknikov Yu. A., Ivanov V. T., Shkkob A. M.:Membrane-Active Complexones (Yu.A. Ovchin-nikov, Ed.). BBA Library Ser. 12. Elsevier, Amsterdam 1974.

    Google Scholar 

  12. Pinkerton M., Steinrauf L. K.: Molecular structure of monovalent metal cation complexes of monensin.J.Mol.Biol. 49, 533 (1970).

    PubMed  Article  CAS  Google Scholar 

  13. PospÍšn, S., Cimburková E., Krumphanzl V., Vanék Z.: Influence of the precursors on the biosynthesis of monensin A and B.Folia Microbiol. 30, 30 (1985).

    Article  Google Scholar 

  14. PospÍšil S., Kbálovcová E., Stajner K., Tax J., KeujiphanzL V., Vaněk Z.: Regulation of biosynthesis of monensis on chemically defined medium.Folia Microbiol. 27, 275(1982).

    Article  Google Scholar 

  15. PospÍšil S., PetebkovÁ M., Krumpbanzl V., Vanék Z.: Regulatory mutants ofStreptomyces cinnamonensis producing monensin A.FEMS Microbiol.Lett. 24 209 (1984).

    Google Scholar 

  16. PospÍšil S., Sedmera P., HavrÁxek M., Krumphaxzl V., Vanék Z.: Biosynthesis of monensins A and B.J.Antibiot. 36, 617 (1983).

    PubMed  Google Scholar 

  17. Pressman B. C., Haynes D. H.:The Molecular Basis of Membrane Function, p. 221. Prentice Hall, New Jersey 1969.

    Google Scholar 

  18. Robinson J. A., Turner D. L.: Total assignment of the carbon-13 XMR spectrum of monensin by two-dimensional correlation spectroscopy.J.Chem.Soc.Ghem.Commun. 1982, 148 (1982).

    Article  Google Scholar 

  19. Thiele O. W.:Lipide, Isoprenoide mit Steroiden, p. 74. Georg Thieme Verlag, Stuttgart 1979.

    Google Scholar 

  20. Umbabgee H. E.: Amino acids biosynthesis and its regulation.Ann.Rev.Biochem. 47, 533 (1978).

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding authors

Correspondence to S. Pospíšil or P. Sedmera or V. Krumphanzl or Z. Vaněk.

Additional information

The authors wish to thank Dr. M. Havránek (Institute of Nuclear Biology and Radiochemistry,Czech.Acad.Sci., Prague) for the synthesis of sodium 1-13C-2-methylbutyrate.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Pospíšil, S., Sedmera, P., Krumphanzl, V. et al. Biosynthesis of monensins a and b: the role of isoleucine. Folia Microbiol 31, 8–14 (1986). https://doi.org/10.1007/BF02928674

Download citation

Keywords

  • Butyrate
  • Isoleucine
  • Monensin
  • Amino Acid Analogue
  • Norleucine