Enhancement of clavulanic acid production by mutant Streptomyces clavuligerus

Background Clavulanic acid CA is a potent beta lactamase inhibitor used to combat resistance to penicillin and cephalosporin antibiotics There are several pathogenic microorganisms that are capable of secreting beta Lactamases These enzymes catalyze the hydrolysis of the beta lactam ring of penicillins and cephalosporins and their hydrolysis products have no antibiotic activity Since the first clinical applications the efficiency of the beta lactam antibiotics has been declining due to the astonishing increasing number of bacteria capable of displaying beta lactam resistance Thus the genetic production improvement using physical and chemical mutagenic agents is an important strategy in programs of industrial production of bioactive metabolites such as CA Objective The objective of the study was to enhance CA production using chemical and UV mutagenesis on Streptomyces clavuligerus Methods nbsp Streptomyces clavuligerus ATCC was used as the standard strain in all the experiments The mutant strain was first obtained by chemical mutagenesis using the agent MMS and next the same strain undergoing one more mutation was obtained by UV light Cellular biomass was analyzed based on the dry weight method and the concentration of CA was determined by HPLC analysis Results CA production increased by with mutant strain when compared to the wild type strain The mutant strain obtained mg L concentration in h of fermentation while the wild type strain obtained only mg L at the same time and the productivity at this moment was and mg L h respectively The mutant strain had a significant increase in biomass growth between and h Conclusion The study showed that random mutations can lead to the improvement in CA production in S clavuligerus This finding reinforces the importance of using this method for productivity improvement