Investigating secondary metabolism in Streptomyces clavuligerus: A known source of medicinally important bioactive natural products

Bacteria from the genus Streptomyces possess diverse secondary metabolic capabilities and produce many compounds that are used in medicine, agriculture and industry. S. clavuligerus produces numerous secondary metabolites including the β-lactamase inhibitor, clavulanic acid. Certain bacterial pathogens produce β-lactamases to inactivate β-lactam family antibiotics, thereby conferring resistance to them. When used in combination with a β-lactam antibiotic, clavulanic acid inhibits β-lactamases, thereby restoring the activity of the β-lactam antibiotic against the target pathogen. There are many commercially available β-lactam antibiotic-clavulanic acid combinations, which are currently prescribed for the treatment of otherwise antibiotic resistant bacterial infections. Clavulanic acid is produced at the industrial scale using S. clavuligerus and the complete regulatory/biosynthetic pathway has not yet been fully elucidated. Therefore, our group is using multiple approaches to study the production of clavulanic acid in S. clavuligerus. In addition, the S. clavuligerus genome sequence has revealed that this organism has the potential to produce in excess of thirty additional secondary metabolites. Our group is also investigating the production and function of some of these previously uncharacterized compounds. An overall review of the S. clavuligerus related projects being pursued by the group and results from some of the studies will be discussed.