Using Small Molecules to Alter Secondary Metabolism in Streptomyces

Abstract

<p>Secondary metabolites produced by bacterial species serve many clinically useful purposes such as anti-bacterial, anti-cancer, and immunosuppresive agents. Actinobacteria, particularly the genus <em>Streptomyces</em>, have been an abundant source of such metabolites for the past half century. The production of secondary metabolites is controlled through vast regulatory cascades, but the activation and control of these pathways is still poorly understood. This leads to the inability to isolate all of the secondary metabolites that <em>Streptomyces</em> are capable of producing. This study focuses on the comparison of synthetic small molecules, which were found to alter the production of secondary metabolites in <em>S. coelicolor</em>. A comparative analysis of two of these molecules, ARC2 and ARC6, shows they modulate secondary metabolites in different ways. In a separate study, ARC2 was shown to achieve this phenotype through the inhibition of a target in fatty acid biosynthesis. The results of this study suggest that ARC6 does not have the same target, although it may target the same metabolic system. Furthermore, these two molecules also have opposite effects on <em>S. coelicolor </em>development. The cumulative results of this study suggest that ARC2 and ARC6 can act as separate chemical tools in enhancing the understanding of secondary metabolism.</p>