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. This proposal outlines studies on the biosynthesis of deazapurine-containing secondary metabolites by bacteria. 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 exploring the chemical transformations that underlies the biosynthesis of these molecules. PUBLIC HEALTH RELEVANCE: Deazapurine-containing compounds are widely distributed in nature and have been shown to have clinically useful activities. Our goal is to understand the chemical transformations that underlie biosynthesis of these compounds in an effort to synthesize additional molecules with improved properties.