Novel antibiotic screening methods to awaken silent or cryptic secondary metabolic pathways in actinomycetes

Streptomyces have the potential to produce more than 30 secondary metabolites; however, the expression of most metabolite biosynthetic gene clusters is cryptic or silent. Indeed, the expression of these genes is conditional and dependent on culture conditions. To activate such gene clusters, many methods have been developed. In this review, I describe two activation approaches developed in my laboratory: use of the activation mediator goadsporin and combined-culture. Goadsporin is a chemical substance isolated from Streptomyces sp. TP-A0584; it induces secondary metabolism and sporulation of many Streptomyces species. Combined-culture is a co-culture method to activate secondary metabolism in Streptomyces. The activator strains are mycolic acid-containing bacteria and ~90% of Streptomyces species show changes in secondary metabolism in combined-culture compared with pure culture. Thus, both methods may have applications in natural product-based drug discovery.