Optimization of medium composition for the production of clavulanic acid by Streptomyces clavuligerus

Abstract The optimization of medium components for the production of clavulanic acid by Streptomyces clavuligerus was performed using both factional factorial design and response surface methodology. The factional factorial design experiment was initially employed for this purpose and it was found that soy meal powder, FeSO 4 ·7H 2 O, and ornithine were the most important medium components (confidence levels above 85%). Response surface methodology for optimization was further investigated. These three composing elements showed significant effects on producing clavulanic acid. Their optimal concentrations were: soy meal powder 38.102 g/l, FeSO 4 ·7H 2 O 0.395 g/l, and ornithine 1.177 g/l. The yield of clavulanic acid was increased by 50% by culturing strain S. clavuligerus in the nutritionally optimized fermentation medium.

[1]  C Reading,et al.  Clavulanic Acid: a Beta-Lactamase-Inhibiting Beta-Lactam from Streptomyces clavuligerus , 1977, Antimicrobial Agents and Chemotherapy.

[2]  A. Brown,et al.  Naturally-occurring beta-lactamase inhibitors with antibacterial activity. , 1976, The Journal of antibiotics.

[3]  G. Rolinson Evolution of β-Lactamase Inhibitors , 1991 .

[4]  M. Bushell,et al.  Manipulation of the physiology of clavulanic acid production in Streptomyces clavuligerus. , 1997, Microbiology.

[5]  H. Kwon,et al.  Enhanced biosynthesis of clavulanic acid in Streptomyces clavuligerus due to oxidative challenge by redox-cycling agents , 1998, Applied Microbiology and Biotechnology.

[6]  P. Germain,et al.  Phosphate repression of cephamycin and clavulanic acid production by Streptomyces clavuligerus , 1987, Applied Microbiology and Biotechnology.

[7]  S. Jensen,et al.  Functional analysis of the gene encoding the clavaminate synthase 2 isoenzyme involved in clavulanic acid biosynthesis in Streptomyces clavuligerus , 1995, Journal of bacteriology.

[8]  J. Houng,et al.  Optimization of glycerol feeding for clavulanic acid production by Streptomyces clavuligerus with glycerol feeding , 2002, Biotechnology Letters.

[9]  Growth limiting substrate affects antibiotic production and associated metabolic fluxes in Streptomyces clavuligerus , 2000, Biotechnology Letters.

[10]  C. Reading,et al.  Assay of amoxicillin and clavulanic acid, the components of Augmentin, in biological fluids with high-performance liquid chromatography , 1982, Antimicrobial Agents and Chemotherapy.

[11]  Carlos O. Hokka,et al.  Optimisation of medium composition for clavulanic acid production byStreptomyces clavuligerus , 2004, Biotechnology Letters.

[12]  J. Martín,et al.  Dissociation of cephamycin and clavulanic acid biosynthesis in Streptomyces clavuligerus , 1984, Applied Microbiology and Biotechnology.

[13]  A. Demain,et al.  Carbon Catabolite Regulation of Cephalosporin Production in Streptomyces clavuligerus , 1978, Antimicrobial Agents and Chemotherapy.