Investigations into the Biosynthesis, Derivatization, and Purification of Jadomycins

Abstract

Nature produces many clinically used medicines in the form of natural products. These compounds can be isolated from a variety of sources, but bacteria have been shown to be the most prolific source. The strain Streptomyces has been thoroughly investigated for such natural products, with Streptomyces venezuelae ISP5230 showing the ability to produce the clinically used antibiotic chloramphenicol, as well as the jadomycins, a family of secondary metabolites. These secondary metabolites are produced through a biosynthetic pathway where the incorporation of the amino acid into the jadomycin structure is likely non-enzymatic. This allows for jadomycins to be readily derivatized, where upwards of twenty-five derivatives have been previously isolated. This work presents the amplification of the jadomycin library through the production of novel jadomycins, as well as their further diversification through the use of synthetic derivatization. The study of jadomycins is not only important chemically, but also biologically because they have been shown to possess anti-cancerous properties. For this reason, the two synthetic derivatives were assessed for biological activities and their results are discussed herein. Investigations were also carried out to develop a method to assess biological activity by nuclear magnetic resonance, and are presented. Finally, investigations into the jadomycin purification methodology were carried out using JadX, a potential regulatory protein in the jadomycin biosynthesis, and are discussed.