Improvement for the production of clavulanic acid by mutant Streptomyces clavuligerus

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Aims:To improve the production of clavulanic acid through the development of strains, the selection of a production medium and a pH shift strategy in a bioreactor.Methods and Results:Streptomyces clavuligerus mutant 15 was selected by antibacterial activities. As a result of pH control in a 2·5 l bioreactor, the highest productivity (3·37 μg ml–1 h–1) was obtained at a controlled pH of 7·0.Conclusions:The highest level of production obtained was an increase of about 36% compared with a non-controlled pH. When the production of clavulanic acid reached the maximum level, the pH was shifted from 7·0 to 6·0 for reduction in decomposition rate. The maximum concentration of clavulanic acid was maintained for 24 h as a result of the pH shift control, and a significant reduction in the decomposition of clavulanic acid was obtained.Significance and Impact of the Study:Clavulanic acid decomposition was considerably reduced as a result of the pH shift control. The results of this study can be applied for the efficient production of β-lactamase inhibitory antibiotics.

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