Effect of Inorganic Salts and Various Bioreactors on the Production of Clavulanic Acid

무기염과 생물반응기의 종류가 Clavulanic acid의 생산에 미치는 영향

  • Published : 1999.08.01

Abstract

For the effecient production of clavulanic acid., a mutant strain Streptomyces clavuligerus KK was selected from Streptomyces clavuligerus ATCC 27064 through mutation with NTG. S. clavuligerus ATCC 27064 produced about 200 mg/L of calvulanic acid when the medium was composed of 1%(W/V) glycerol, 1.5%(W/V) soybean flour, 0.1%(W/V) $KH_2PO_4$, 0.2%(V/V) soybean oil. A selected mutant, S. clavuligerus KK, produced about 1150 mg/L of clavulanic acid in the same medium. After the addition of $MgSO_4$ to the basal medium, S. clavuligerus KK produced about 1550 mg/L of clavulanic acid, with shows about 1.3 times higher than that produced in the basal medium. In order to select the proper bioreactor for the production of clavulanic acid, a batch culture was performed in an airlift, a bubble column and an stirred tank bioreactors. In an airlift bioreactor, about 1350 mg/L of clavulanic acid was produced, in a bubble column bioreactor, about 1550 mg/L, in a stirred tank bioreactor, about 2200 mg/L, respectively. The production of clavulanic acid in stirred tank bioreactor was about 50% higer than that by an airlift and a bubble column bioreactors. According to this result, the stirred tank bioreactor was selected as a proper bioreactor.

References

  1. Appl. Microbiol. Biotechnol. v.20 Dissociation of cephamycin and clavulanic acid biosynthesis in Streptomyces clavuligerus Romero, J.;P. Liras;J. F. Martin
  2. Appl. Microbiol. Biotechnol. v.27 Isolation and biochemical characterization of Streptomyces clavuligerus mutants in the biosynthesis of clavulanic acid and cephamycin C Romero, J.;P. Liras;J. F. Martin
  3. Biochemistry v.17-11 Kinetic studies on the Inactivation of Escherichia coli RTEM β-lactamase by clavulanic acid Fisher, J.;R. L. Charnas;J. R. Knowles
  4. Clavulanic acid : Properties, Biosynthesis, and Fermentation Butterworth, D.
  5. Reviews of Infectious Diseases v.13 Evolution of Beta-lactamase inhibitors Rolinson, G. N.
  6. J. Antibiot. v.29 Naturally occuring β-lactamase inhibitors with antibacterial activity Brown, A. G.;D. Butterworth;M. Cole;G. Hanscomb;J. D. Hood;C. Reading;G. N. Rolinson
  7. Antimicrob. Agents. chemo. v.12-3 Binding of thienamycin and clavulanic acid to the penicillin-binding proteins of Escherichia coli k-12 Spratt, B. G.;V. Jobanputra;W. Zimmermann
  8. Antimicrob. Agents. Chemo. v.11-5 Clavulanic acid : a beta-lactamase-inhibiting beta-alctam from Streptomyces clavuligerus Reading, C.;M. Cole
  9. Biotechnol. Bioeng. v.37 Morphology and clavulanic acid production of Streptomyces clavuligerus: Effect of stirrer speed in batch fermentation Belmar-Beiny, M. T.;C. R. Thomas
  10. Micorbiology v.142 Cell density influences antiobiotic biosynthesis in Streptomyces clavuligerus Sanchez, L.;A. F. Brana
  11. Appl. Microbiol. Biotechnol. v.45 Simultaneous production and decomposition of clavulanic acid during Streptomyces clavuligerus cultivation Mayer, A. F.;W. D. Deckwer
  12. Biotechnology of Industrial Antibiotics Vandamme, E. J.