Biosynthesis of deazapurine-containing metabolites

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DESCRIPTION (provided by applicant): All organisms produce a host of compounds that are generally not required in primary metabolic processes, but play important regulatory functions. These secondary metabolites have been exploited by every civilization to enhance life and cure human diseases. We know these as hormones, antibiotics, antitumor agents, and antivirals. Since these metabolites can harm cells if produced in excess, or if present when a need for them does not exist, their production is often strictly regulated. An understanding of how cells synthesize and regulate the production of secondary metabolites is essential if one is to be able to exploit them as human therapeutic agents. Deazapurines are secondary metabolites that are derived from purines and little is known about how they are synthesized in the cell. This proposal outlines studies on the biosynthesis of deazapurine-containing secondary metabolites by Streptomyces. Our goal is to bring to fore the tools of genomics, molecular biology and enzymology to form the framework of how these metabolites are synthesized, and to begin the process of exploring the chemistry that underlies the biosynthesis of these molecules.