Challenges attending upon studies on clavulanic acid production

In nature, microorganisms produce tiny amounts of secondary metabolic products as a matter of survival. Genetic manipulations are used in industry to obtain strains that produce hundreds or thousands of times more than that produced by the originally isolated strain. These strain improvement traditionally employ mutagenesis followed by screening or selection. Clavulanic acid (CA), a potent beta-lactamase inhibitor, is produced by strains of Streptomyces clavuligerus in submerged cultures. The aim of this paper was to report the advances achieved so far in our laboratories, in terms of strain improvement and bioprocess optimization involving oxygen supply, fedbatch operation and air-lift bioreactor design. We also report on our research into bioactive substances in endophytic microorganisms.