1887

Abstract

Production of cephamycin C and clavulanic acid by took place during the exponential phase of growth in a defined medium. Both antibiotic biosynthetic pathways were activated shortly after spore germination, but the timing and kinetics of activation were affected by inoculum density. Rapid activation was favoured by high inoculum density or by growth in medium conditioned by previous incubation of spores or mycelium. A heat-resistant conditioning factor able to accelerate the acquisition of antibiotic-biosynthetic capacity when added to low-density cultures was released in suspensions of spores in water. Conditioning factor was also obtained in suspensions of spores from different species or of cells, indicating that the signal was not produced specifically by . Fractionation of conditioning factor showed that its effect was not due to a single molecule. The fractions contained amino acids (as free amino acids and oligopeptides) in amounts that roughly correlated with their respective conditioning power. Furthermore, the conditioning effect was reproduced by supplementing defined medium with amino acids and peptides in concentrations that mimicked those found in conditioning factor. When individually tested at concentrations in the micromolar range, only some amino acids were able to stimulate antibiotic biosynthetic capacity. This stimulation was also promoted by low concentrations (less than 1 μg ml) of peptide mixtures obtained with different proteolytic enzymes. The results suggest that both amino acids and peptides are responsible for the effects of conditioning factor released by spores. Possible implications of intercellular signalling on activation of secondary metabolism are discussed.

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1996-05-01
2021-04-18
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References

  1. Anzai H., Murakami T., Imai S., Satah A., Nagaoka K., Thompson C.J. Transcriptional regulation of bialaphos biosynthesis in Streptomyces hygroscopicus. J Bacterioi 1987; 169:3482–3488
    [Google Scholar]
  2. Bascarán V., Sánchez L., Hardisson C., Braña A.F. Stringent response and initiation of secondary metabolism in Streptomyces clavuligerus. J Gen Microbiol 1991; 137:1625–1634
    [Google Scholar]
  3. Bok S.H., Demain A.L. An improved assay for polyols. Anal Biochem 1977; 81:18–20
    [Google Scholar]
  4. Bradford M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72:248–254
    [Google Scholar]
  5. Braña A.F., Wolfe S., Demain A.L. Ammonium repression of cephalosporin production by Streptomyces clavuligerus. Can J Microbiol 1985; 31:736–743
    [Google Scholar]
  6. Bushell M.E., Fryday A. The application of materials balancing to the characterization of sequential secondary metabolite formation in Streptomyces cattleya NRRL 8057. J Gen Microbiol 1983; 129:1733–1741
    [Google Scholar]
  7. Champness W., Riggle P., Adamidis T., Vandervere P. Identification of Streptomyces coelicolor genes involved in regulation of antibiotic biosynthesis. Gene 1992; 115:55–60
    [Google Scholar]
  8. Chater K.F. Genetics of differentiation in Streptomyces. Annu Rev Microbiol 1993; 47:685–713
    [Google Scholar]
  9. Clewell D.B. Bacterial sex pheromone-induced plasmid transfer. Cell 1993; 73:9–12
    [Google Scholar]
  10. Fernández Moreno M.A., Martín Triana A.J., Martínez E., Niemi J., Kieser H.M., Hopwood D.A., Malpartida F. aba A, a new pleiotropic regulatory locus for antibiotic production in Streptomyces coelicolor. J Bacterioi 1992; 174:2958– 2967
    [Google Scholar]
  11. Foulstone M., Reading C. Assay for amoxicillin and clavulanic acid, the components of augmentin, in biological fluids with high performance liquid chromatography. Antimicrob Agents Chemother 1982; 22:753–762
    [Google Scholar]
  12. Fuqua W.C., Winans S.C., Greenberg E.P. Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J Bacteriol 1994; 176:269–275
    [Google Scholar]
  13. Geistlich M., Losick R., Turner J.R., Rao R.N. Characterization of a novel regulatory gene governing the expression of a polyketide synthase gene in Streptomyces ambofaciens. Mol Microbiol 1992; 6:2019–2029
    [Google Scholar]
  14. Grossman A.D., Losick R. Extracellular control of spore formation in Bacillus subtilis. Proc Natl AcadSci USA 1988; 85:4369–4373
    [Google Scholar]
  15. Hill D.W., Walters F.M., Wilson D., Stuart J.D. High performance liquid chromatographic determination of amino acids in the picomole range. Anal Chem 1979; 51:1338–1341
    [Google Scholar]
  16. Hobbs G., Frazer C.M., Gardner D.C.J., Flett F., Oliver S.G. Pigmented antibiotic production by Streptomyces coelicolor A3(2): kinetics and the influence of nutrients. J Gen Microbiol 1990; 136:2291–2296
    [Google Scholar]
  17. Horinouchi S., Beppu T. Regulation of secondary metabolism and cell differentiation in Streptomyces: A-factor as a microbial hormone and the AfsR protein as a component of a two-component regulatory system. Gene 1992a; 115:167–172
    [Google Scholar]
  18. Horinouchi S., Beppu T. Autoregulatory factors and communication in actinomycetes. Annu Rev Microbiol 1992b; 46:377–398
    [Google Scholar]
  19. Ishizuka H., Horinouchi S., Kieser H.M., Hopwood D.A., Beppu T. A putative two-component regulatory system involved in secondary metabolism in Streptomyces spp. J Bacteriol 1992; 174:7585–7594
    [Google Scholar]
  20. Kaiser D., Losick R. How and why bacteria talk to each other. Cell 1993; 73:873–885
    [Google Scholar]
  21. Kuspa A., Plamann L., Kaiser D. Identification of heat-stable A-factor from Myxococcus xanthus. J Bacteriol 1992a; 174:3319–3326
    [Google Scholar]
  22. Kuspa A., Plamann L., Kaiser D. A-signalling and the cell density requirement for Myxococcus xanthus development. J Bacteriol 1992b; 174:7360–7369
    [Google Scholar]
  23. Laville J., Voisard C., Keel C., Maurhofer M., Dgfago G., Haas D. Global control in Pseudomonas fluorescens mediating antibiotic synthesis and suppression of black root rot of tobacco. Proc Natl Acad Sci USA 1992; 89:1562–1566
    [Google Scholar]
  24. Magnuson R., Solomon J., Grossman A.D. Biochemical and genetic characterization of a competence pheromone from B. subtilis. Cell 1994; 77:207–216
    [Google Scholar]
  25. Malpartida F., Hopwood D.A. Physical and genetic characterization of the gene cluster for the antibiotic actinorhodin in Streptomyces coelicolor. Mol Gen Genet 1986; 205:66–73
    [Google Scholar]
  26. Marahiel M.A., Nakano M.M., Zuber P. Regulation of peptide antibiotic production in Bacillus. Mol Microbiol 1993; 7:631–636
    [Google Scholar]
  27. Martin J.F., Demain A.L. Control of antibiotic synthesis. Microbiol Rev 1980; 44:230–251
    [Google Scholar]
  28. Matsumoto A., Hong S.-K., Ishizuka H., Horinouchi S., Beppu T. Phosphorylation of the AfsR protein involved in secondary metabolism in Streptomyces species by a eukaryotic-type protein kinase. Gene 1994; 146:47–56
    [Google Scholar]
  29. Nagarajan R., Boeck L.D., Gorman M., Hamill R.L., Higgens C.E., Hoehn M.M., Stark W.M., Whitney J.G. β-Lactam antibiotics from Streptomyces. J Am Chem Soc 1971; 93:2308–2310
    [Google Scholar]
  30. Narva K.E., Feitelson J.S. Nucleotide sequence and transcriptional analysis of the redD locus of Streptomyces coelicolor A3(2). J Bacteriol 1990; 172:326–333
    [Google Scholar]
  31. Neidhardt F.G., Ingraham J.L., Schaechter M. Physiology of the Bacterial Cell: a Molecular Approach 1990 Sunderland, MA: Sinauer Associates;
    [Google Scholar]
  32. O'Sullivan J., Aplin R.T., Stevens C.M., Abraham E.P. Biosynthesis of a 7-a-methoxycephalosporin. Incorporation of molecular oxygen. Biochem J 1979; 179:47–52
    [Google Scholar]
  33. Pearce B.J., Naughton A.M., Masure H.R. Peptide permeases modulate transformation in Streptococcus pneumoniae. Mol Microbiol 1994; 12:881–892
    [Google Scholar]
  34. Perego M., Higgins G.F., Pearce S.R., Gallagher M.P., Hoch J.A. The oligopeptide transport system of Bacillus subtilis plays a role in the initiation of sporulation. Mol Microbiol 1991; 5:173–185
    [Google Scholar]
  35. Piepersberg W., Distler J., Ebert A., Heinzel P., Mansouri K., Mayer G., Pissowotzki K. Expression of genes for streptomycin biosynthesis. In Biology of Actinomycetes ’88 1988 Edited by Okami Y., Beppu T., Ogawara H. Tokyo: Japan Scientific Societies Press; pp 86–91
    [Google Scholar]
  36. Romero J., Liras P., Martin J.F. Dissociation of cephamycin and clavulanic acid biosynthesis in Streptomyces clavuligerus. Appl Microbiol Biotechnol 1984; 20:318–325
    [Google Scholar]
  37. Rudner D.Z., Le Deaux J.R., Ireton K., Grossman A.D. The spoOK locus of Bacillus subtilis is homologous to the oligopeptide permease locus and is required for sporulation and competence. J Bacteriol 1991; 173:1388–1398
    [Google Scholar]
  38. Stutzman-Engwall K.J., Otten S.L., Hutchinson C.R. Regulation of secondary metabolism in Streptomyces spp. and overproduction of daunorubicin in Streptomyces peucetius. J Bacteriol 1992; 174:144–154
    [Google Scholar]
  39. Weatherburn M.W. Phenol-hypochlorite reaction for determination of ammonia. Anal Chem 1967; 39:971–974
    [Google Scholar]
  40. Willey J., Schwedock J., Losick R. Multiple extracellular signals govern the production of a morphogenetic protein involved in aerial mycelium formation by Streptomyces coelicolor. Genes Dev 1993; 7:895–903
    [Google Scholar]
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