Streptomyces clavuligerus: The Producer Organism of Clavulanic Acid

Clavulanic acid is a major β-lactam antibiotic and a powerful inhibitor of the beta-lactamases, enzymes produced by bacteria, which are resistant to penicillin and cephalosporin. The industrial production of clavulanic acid is carried out by large-scale fermentation of Streptomyces clavuligerus. Since the first clinical applications, the efficiency of the β-lactam antibiotics has been declining, due to the astonishing increasing number of bacteria capable of displaying β-lactam resistance. Such resistance is due to pathogenic microorganisms that produce β-lactamaseenzymes, the most important mechanism of bacterial β-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 clavulanic acid. This review focused on the biosynthesis, improvement and the importance of future investigations on clavulanic acid.