Activation of the Cryptic Secondary Metabolite Biosynthetic Gene Clusters in Actinomycetes by Antibiotics Resistance

Abstract

Actinomycetes produce a variety of natural products that are of major importance in the agrochemical and pharmaceutical industry. More than 50% of all anti-infective and anticancer compounds developed over the past 25 years have been natural products or derivatives thereof. Recent advances in genome sequencing have revealed that such organisms have the potential to yield even more structurally diverse secondary metabolites. Thus, many microbial gene clusters may be silent under standard laboratory growth conditions. In the last ten years, several strategies have been applied to the activation of microbial cryptic biosynthetic pathways, like OSMAC, heterologous expression and homologous, co-cultivation and ribosome engineering. Among them, the ribosome engineering seems more attractive due to the fact of not requiring the global knowledge of the bacterial genome. This project aims to apply the ribosome engineering to generate mutants from three strains of actinomycetes (CAAT 1-54, EUCAL 26 and CAAT 2-63), previously studied in our laboratory, to evaluate the overproduction of antibiotics and also the identification of cryptic new secondary metabolites by LC-MS/MS from mutants. (AU)