8. Genome Guided Discovery of Chlorinated Natural Products in Streptomyces curacoi

Abstract

Natural products derived from plants, animals, and microbes have long been a rich source of molecules that exhibit biological activity. Bacteria of the genus Streptomyces are one of the most important sources of natural products today, producing more than half of all known antibiotics. One class of natural products that have potent antibiotic activity are those that contain halogens. There are many examples of halogenated natural products such as the antibiotics vancomycin and chloramphenicol. Incorporation of halogen atoms into drugs is a common strategy to enhance their bioactivity and specificity.
 Rapid advances in DNA sequencing have led to genome mining approaches to discover new natural products. This technique can also be used to find bioactive halogenated products by analyzing the genomes for sequences encoding the ‘halogenases’ that are responsible for addition of the halogen.
 One class of compounds that have biological activity against Streptococcus pneumoniae, Staphylococcus aureus, and Staphylococcus epidermidis are the desotamides. These compounds inhibit bacterial RNA polymerases. A cluster of genes that is likely responsible for the production this compound has been discovered in the Streptomyces curacoi genome; however this cluster is unique in that it also contains a halogenase gene. This study aims to discover a halogenated desotamide derivative from Streptomyces curacoi based on the genomic information. It is hypothesized that this derivative will have enhanced or new biological activity.