Biosynthetic Investigations of the Peptide Natural Products K-26 and Anthramycin
The dissertation contained herein describes biosynthetic investigations of the peptide natural products K-26 and anthramycin. Unified by their peptidic nature, K 26 and anthramycin are potent biologically active metabolites whose biosynthetic mechanisms of formation have remained cryptic. Based on the inclusion of non-proteinogenic amino acids, it is highly likely that both of these natural products are formed via a non-ribosomal peptide synthetase pathway. Chapter I describes the initial discovery of these compounds, initial experiments investigating the amino acid precursors of these metabolites and the possible biosynthetic route for the formation of their peptide bond formation. Chapter II describes the development of a mass-based pyrophosphate exchange assay used to probe the potential nonribosomal biosynthesis of these natural products. Chapter III describes the investigation of K 26 biosynthesis in Astrosporangium hypotension. Chapter IV describes the investigation of anthramycin biosynthesis in Streptomyces refuineus sbsp. thermotolerans. Chapter V discusses possible future investigations for both natural products.