Exploring the Optimization of UV Mutants of Streptomyces clavuligerus for Clavulanic Acid Production

Streptomyces clavuligerus, initially described as a Cephamycin C producer, has been currently utilized to produce clavulanic acid (CA) which shows low antibiotic activity, being, however, a strong β-lactamase inhibitor, enzymes responsible for bacterial resistance to β–lactam antibiotics. Genetic improvement by physical and chemical agents is mandatory since, due to its genetic instability, industrial strains lose production capability making necessary a steady and frequent strain improvement and a screening procedure. The objective of this work was to obtain an increase in CA production in submerged cultures by utilizing mutants obtained by UV radiation of the wild strain Streptomyces clavuligerus ATCC 27064. Submerged cultures were performed, with the best mutants selected, in a 5L bench-scale bioreactor, batch-wise, utilizing a complex medium containing glycerol and a soybean protein isolate as the main components. The mutant 70 was able to produce a maximum CA concentration of 500 mg.L-1, approximately 1.6 times higher than the wild strain. Another finding was a higher CA productivity of 29.5 mg.h-1.L-1 with this mutant, although a lower specific growth rate had been observed.