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Secondary Metabolite Production in Sorangium cellulosum

$195,000R15FY2007CANIH

Emporia State University, Emporia KS

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): The myxobacteria are a group of bacteria ubiquitous in nature. Studies in the last 25 years have demonstrated these organisms produce a host of novel secondary metabolites. Current estimates suggest approximately 50% of all myxobacterial strains produce a bioactive molecule. For some myxobacteria, such as the cellulose-degrading Sorangium cellulosum, this estimate nears 100%. S. cellulosum is best known for its production of epothilones, which are secondary metabolites that possess a mode of action similar to Taxol. Since this organism's genome is approximately 12 million base pairs, the genetic potential for secondary metabolite production is significant. Unfortunately, it's slow growth, copious production of slime, and variable appearance make identification and propagation difficult, resulting in few laboratories involved in new strain isolation. Although several S. cellulosum metabolites have been described in the literature, the vast potential of this organism remains largely unexplored. The broad, long-term goal of this project is to access the capacity of S. cellulosum to produce biologically significant molecules. Our working hypothesis is that since this organism is largely understudied as compared to other secondary metabolite producing organisms, many new biologically active metabolites remain to be discovered. To address this hypothesis, aim 1) of this project will be to isolate new S. cellulosum strains and propagate a historical collection of S. cellulosum known as the Peterson collection. Once strains are isolated, the goal of aim 2) will be to determine the biological activity of S. cellulosum extracts using the National Cancer Institute Yeast Anticancer Drug Screen and to generate a high performance liquid chromatography profile of each extract. Once a strain is identified which produces a metabolite of interest, the goal of aim 3) is to optimize fermentation conditions for production of the molecule of interest followed by its purification. Students pursuing both B.S. and M.S. degrees will be involved in all aspects of this project. Sorangium cellulosum is a bacterium that produces a wide array of molecules that may benefit human health. This project will attempt to identify S. cellulosum isolates that may be producing these molecules followed by their purification. [unreadable] [unreadable] [unreadable]

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