Isolation and characterization of jadomycin L from Streptomyces venezuelae ISP5230 for solid tumor efficacy studies

Abstract

Precursor-directed biosynthesis offers opportunities to modify natural products and obtain structurally complex metabolites without the need for chemical synthesis. However, such opportunities are limited owing to the inherent substrate specificity of biosynthetic enzymes. The jadomycins are a family of natural products produced by the soil microbe Streptomyces venezuelae ISP5230. Their biosynthesis contains one step that is potentially non-enzymatic, namely, the condensation of a biosynthetic aldehyde and an amino acid that leads to a uniquely substituted oxazolone ring. Variation of amino acids in the culture media enables the production of a wide array of substituted oxazolones. These analogs have been shown to have a variety of biological activities against cancer cell lines and also against Gram-positive bacteria. Herein, we report the first isolation and characterization of jadomycin L and jadomycin L aglycone from 8 L of bacterial culture for solid tumor efficacy studies.