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Effect of aeration on antibiotic production byStreptomyces clavuligerus

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Journal of Industrial Microbiology

Summary

During the rapid growth phase ofStreptomyces clavuligerus in a 10 litre fermentor, the level of dissolved oxygen (DO) was found to drop to almost zero for a period of approximately 10 h, delaying the appearance of and lowering the production of the antibiotic cephamycin C. Controlling the DO at either 50% or 100% throughout the fermentation did not significantly alter the specific growth rate of the culture, but did elevate final antibiotic levels two- and three-fold respectively. The improved oxygen availability affected antibiotic production both by increasing the rate of specific cephamycin C bisosynthesis and by maintaining this higher rate throughout the production period. These results demonstrate that controlling dissolved oxygen levels close to saturation during periods of rapid growth markedly improves the efficiency and duration of cephamycin C biosynthesis inS. clavuligerus.

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References

  1. Abraham, E.P., J.A. Huddleston, G.S. Jayatilake, J. O'Sullivan and R.L. White. 1981. Conversion of δ-(l-α-aminoadipyl)-l-cysteinyl-d-valine to isopenicillin N in cell-free extracts ofCephalosporium acremonium. In: Recent Advances in the Chemistry ofβ-lactam Antibiotics (2nd International Symposium) (Gregory, G.I., ed.), pp. 125–134, Special Publication, The Royal Society of Chemistry, London.

    Google Scholar 

  2. Agathos, S.N. and A.L. Demain. 1986. Dissolves and the in vivo stability of gramicidin S synthetase. Appl. Microbiol. Biotechnol. 24: 319–322.

    Google Scholar 

  3. Aharonowitz, Y. and A.L. Demain. 1979. Nitrogen nutrition and regulation of cephalosporin production inStreptomyces clavuligerus. Can. J. Microbiol. 25: 61–67.

    PubMed  Google Scholar 

  4. Aharonowitz, Y., S. Mendelovitz, F. Kirenberg and V. Kuper. 1984. Regulatory mutants ofStreptomyces clavuligerus affected in free diaminopimelic acid content and antibiotic biosynthesis. J. Bacteriol. 157: 337–340.

    PubMed  Google Scholar 

  5. Bradford, M. 1976. A rapid, sensitive method for the quantion of microgram quantities of protein using the principle of protein-dye binding. Anal Biochem. 72: 248–254.

    Google Scholar 

  6. Flickinger, M.C. and D. Perlman. 1979. Application of oxygen-enriched aeration in the production of bacitracin byBacillus licheniformis. Antimicrob. Agents Chemother. 15: 282–293.

    PubMed  Google Scholar 

  7. Friebel, T.E. and A.L. Demain. 1977. Oxygen-dependent inactivation of gramicidin S synthetase inBacilus brevis. J. Bacteriol. 130: 1010–1016.

    PubMed  Google Scholar 

  8. Gaucher, G.M., K.S. Lam, J.W.D. GrootWassink, J. Neway and Y.M. Deo. 1981. The initiation and longevity of patulin biosynthesis. Dev. Ind. Microbiol. 22: 219–232.

    Google Scholar 

  9. Hanlon, G.W. and N.A. Hodges. 1981. Bacitracin and protease production in relation to sporulation during exponential growth ofBacillus licheniformis on poorly utilized carbon and nitrogen sources. J. Bacteriol. 147: 427–431.

    PubMed  Google Scholar 

  10. Higgens, C.E., R.L. Hamill, T.H. Sands, M.M. Hoehn, N.E. Davis, R. Nagarajan and L.D. Boeck. 1974. The occurrence of deacetoxycephalosporin C in fungi andStreptomyces. J. Antibiot. 27: 298–300.

    PubMed  Google Scholar 

  11. Hopwood, D.A., M.J. Bibb, K.F. Chater, T. Kieser, C.J. Bruton, H.M. Kieser, D.J. Lydiate, C.P. Smith, J.M. Ward and H. Schrempf. 1985. Preparation of organisms and phages. In: Genetic Manipulation of Streptomyces. A Laboratory Manual. The John Innes Foundation.

  12. Jensen, S.E., B.K. Leskiw, L.C. Vining, Y. Aharonowitz and D.W.S. Westlake. 1986. Purification of isopenicillin N synthetase fromStreptimyces clavuligerus. Can. J. Microbiol. 32: 953–958.

    PubMed  Google Scholar 

  13. Jensen, S.E., D.W.S. Westlake and S. Wolfe. 1982. Cyclization of δ(l-α-aminoadipyl)-l-cysteinyl-d-valine to penicillins by cell-free extracts ofStreptomyces clavuligerus. J. Antibiot. 35: 483–490.

    PubMed  Google Scholar 

  14. Koplove, N.M. and C.L. Cooney. 1979. Enzyme production during transient growth: the reorganization of protein synthesis. In: Advances in the Biochemical Engineering of Immobilized Enzymes II, Vol. 12 (Ghose, T.K., A. Fiechter and N. Blakebrough, eds.), pp. 1–40, Springer-Verlag, Berlin.

    Google Scholar 

  15. Lilley, G., A.E. Clark and G.C. Lawrence. 1981. Control of the production of cephamycin C and thienamycin byStreptomyces cattleya NRRL 8057. J. Chem. Tech. Biotechnol. 31: 127–134.

    Google Scholar 

  16. Matteo, C.C., C.L. Cooney and A.L. Demain. 1976. Production of gramicidin S synthetases byBacillus brevis in continuous culture. J. Gen. Microbiol. 96: 415–422.

    PubMed  Google Scholar 

  17. Revilla, G., F.R. Ramos, M.J. Lopez-Nieto, E. Alvarez and J.F. Martin. 1976. Glucose represses formation of δ(l-α-aminoadipyl)-l-cysteinyl-d-valine and isopenicillin N synthase but not penicillin acyltransferase inPenicillium chrysogenum. J. Bacteriol. 167: 947–952.

    Google Scholar 

  18. Sawada, Y., T. Konomi, N.A. Solomon and A.L. Demain. 1980. Increase in activity of β-lactam synthetases after growth ofCephalosporium acremonium with methionine or norleucine. FEMS Microbiol. Lett. 9: 281–284.

    Google Scholar 

  19. Seddon, B. and G.H. Fynn. 1973. Energetics of growth in a tyrothricin-producing strain ofBacillus brevis. J. Gen. Microbiol. 74: 305–314.

    PubMed  Google Scholar 

  20. Turner, M.K., J.E. Farthing and S.J. Brewer. 1978. The oxygenation of [3-methyl-3H]-desacetoxycephalosporin C [7β-(5-d-aminoadipamido)-3-methylceph-3-em-4-carboxylic acid] to [3-hydroxymethyl-3H]desacetylcephalosporin C by 2-oxoglutarate-linked dioxygenases fromAcremonium chrysogenum andStreptomyces clavuligerus. Biochem. J. 173: 839–850.

    PubMed  Google Scholar 

  21. Vandamme, E.J., D. Leyman, P. De Visscher, D. DeBuyser and G. Vansteenkiste. 1981. Effect of aeration and pH on gramicidin S production byBacillus brevis. J. Chem. Tech. Biotechnol. 31: 247–257.

    Google Scholar 

  22. Vardar, F. and M.D. Lilly. 1982. Effect of cycling D.O. concentrations on product formation in penicillin fermentations. Eur. J. Appl. Microbiol. Biotechnol. 14: 203–211.

    Google Scholar 

  23. Vu-Trong, K. and P.P. Gray. 1982. Stimulation of tylosin productivity resulting from cyclic feeding profiles in fed batch cultures. Biotechnol. Lett. 4: 725–728.

    Google Scholar 

  24. Vu-Trong, K. and P.P. Gray. 1984. Stimulation of enzymes involved in tylosin biosynthesis by cyclic feeding profiles in fed batch cultures. Biotechnol. Lett. 6: 435–440.

    Google Scholar 

  25. Wang, D.I.C. and R.C.L. Fewkes. 1977. Effect of operating and geometric parameters on the behaviour of non-newtonian, mycelial, antibiotic fermentations. Dev. Ind. Microbiol. 18: 39–56.

    Google Scholar 

  26. Zhang, J.-y., G. Banko, S. Wolfe and A.L. Demain. 1987. Methionine induction of ACV synthetase inCephalosporium acremonium. J. Ind. Microbiol. 2: 251–255.

    Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology, University of Alberta, T6G 2E9, Edmonton, Alberta, Canada

    Malcolm J. Rollins, Susan E. Jensen & Donald W. S. Westlake

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  1. Malcolm J. Rollins
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  2. Susan E. Jensen
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  3. Donald W. S. Westlake
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Rollins, M.J., Jensen, S.E. & Westlake, D.W.S. Effect of aeration on antibiotic production byStreptomyces clavuligerus . Journal of Industrial Microbiology 3, 357–364 (1988). https://doi.org/10.1007/BF01569557

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