Specialized metabolism in the Streptomyces: lessons from clavulanic acid biosynthesis

Historically, some of the most successful antibiotics used for treating bacterial infections were derived from natural products, which also include compounds produced by other bacteria. These compounds are normally synthesized using specialized pathways and genes, which are overrepresented in some microorganisms. The β-lactam family of natural products have a long history of human use, but resistance has always posed a challenge. The bacterium Streptomyces clavuligerus produces the clinically used β-lactamase inhibitor, clavulanic acid, and also contains genes for making many natural products, but only a few are produced under laboratory conditions. Therefore, these so called unknown or “cryptic” genes could be sources of novel compounds. The long-term goal of our work is to fully understand the mechanisms controlling the biosynthesis of clavulanic acid and other natural products in S. clavuligerus and related bacteria, to exploit their potential for producing bioactive compounds for future applicants.