Abstract
In order to obtain high productivity of clavulanic acid, a newly-introduced carrier, polyurethane pellet (PUP) Z97-020 was used for the immobilization process. In a stirred-tank bioreactor, batch cultivation by Streptomyces clavuligerus KK immobilized on PUP Z97-020 gave about 3100 mg of clavulanic acid per litre, representing an increase of 200% in productivity compared with that by fed-batch cultivation of free cells (1500 mg/l). However, the clavulanic acid produced rapidly decomposed due to the pH change during batch cultivation. Fed-batch cultivation by immobilized S. clavuligerus KK gave an excellent level of clavulanic acid up to 3250 mg/l, a productivity increase of 220% compared with that by fed-batch cultivation of free cells. These results suggest that immobilization with PUP Z97-020 is a more effective process for the production of clavulanic acid and that the maintenance of pH by fed-batch cultivation with glycerol as a limiting substrate prevents the clavulanic acid from decomposing during the fermentation.
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References
Butterworth, D. 1984 Clavulanic acid: Properties, Biosynthesis, and Fermentation, In: Vandamme E.J., ed. Biotechnology of Industrial Antibiotics, Marcel Dekker, Inc., pp. 225-235. ISBN 0-82477056-0.
Brown, A.G., Butterworth, D., Cole, M., Hanscomb, G., Hood, J.D., Reading, C. & Rolinson, G.N. 1976 Naturally occurring β-lactamase inhibitors with antibacterial activity. Journal of Antibiotics 29, 668-669.
El-sayed, A.M.M., Mahmoud, W.M. & Coughlin, R.W. 1990 Production of dextransucrase by Leeconostoc mesenteroides immobilized in calcium-alginate beads, batch and fed-batch fermentation. Biotechnology and Bioengineering 36, 338-345.
Hopwood, D.A. 1981 Genetic studies of antibiotics and other secondary metabolites. In: Genetics as a Tool in Microbiology (Symposia of the Society for General Microbiology) 31, 187-218.
Kim, I.C. & Kim, S.W. 1998 Production and characteristics of clavulanic acid. Bioindustry News 11, 22-27.
Kim, I.C. & Kim, S.W. 1999 Effect of inorganic salts and various bioreactors on the production of clavulanic acid. Korean Journal of Biotechnology and Bioengineering 14, 440-444.
Mayer, A.F. & Deckwer, W.D. 1996 Simultaneous production and decomposition of clavulanic acid during Streptomyces clavuligerus cultivation. Applied Microbiology and Biotechnology 45, 41-46.
Mohagheghi, A., Grohmann, K. & Wyman, E. 1990 Production of cellulase on mixtures of xylose and cellulose in a fed-batch process, Biotechnology and Bioengineering 35, 211-216.
Reading, C. & Cole, M. 1977 Clavulanic acid: a beta-lactamase-inhibiting beta-lactam from Streptomyces clavuligerus, Antimicrobial Agents and Chemotheraphy 11–5, 852-857.
Rolinson, G.N. 1991 Evolution of Beta-lactamase inhibitors, Review of Infectious Diseases 13, S727-S732.
Romero, J., Liras, P. & Martin, J.F. 1988 Isolation and biochemical characterization of Streptomyces clavuligerus mutants in the biosynthesis of clavulanic acid and cephamycin C*, Applied Microbiology and Biotechnology 27, 510-516.
Sam, K. & Stephanopoulos, G. 1989 Optimization of fed-batch penicillin fermentation, Biotechnology and Bioengineering 34, 72-78.
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Kim, IC., Kim, CH., Hong, SI. et al. Fed-batch cultivation for the production of clavulanic acid by an immobilized Streptomyces clavuligerus mutant. World Journal of Microbiology and Biotechnology 17, 869–872 (2001). https://doi.org/10.1023/A:1013895617923
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DOI: https://doi.org/10.1023/A:1013895617923