Marine actinomycetes : the search for secondary metabolites with Sir2p inhibition

Actinomycete bacteria from marine sources provide novel secondary metabolites that\ud serve as the basis for drug discovery. These actinomycetes are commonly found in\ud sediments and act as symbionts of marine organisms. Actinomycete species vary\ud considerably due to differences in their environment such as differences in salinity,\ud temperature, and pressure. Actinomycete derived compounds can be isolated, purified,\ud and identified using isolation techniques following with structure elucidation. Due to the\ud ever growing phylum of actinobacteria, new species are being discovered and thus\ud promises new possibilities in unique and various natural products. In particular, our\ud natural products are being isolated based on their ability to target and inhibit a yeast\ud transcriptional repressor Sir2p, a homolog of a class III histone deacetylases, Sirt,\ud commonly over-expressed in cancer cells. Thus by identifying compounds that inhibit\ud Sir2p, one can correlate this compounds functionality as an anticancer drug. Our results\ud show the isolation, purification, identification and Sir2p activities of five isoflavones\ud genistein, derived from the actinomycete Nonomuraea rubescens, and genistin, glycitin,\ud prunetin, and daidzein isolated from Streptomyces species. This research explores the\ud methodology and discovery of secondary metabolites that can potentially serve medicinal\ud chemistry as a chemotherapeutics, derived from the vast and unique phylum of marine\ud actinomycete bacteria