Unconventional approaches to search for bioactive microbial natural products

Abstract

This project aims to use two unconventional approaches to obtain microbial natural products, especially bioactive ones: metagenomics and interespecific interactions. This proposal contemplates one of the main prerequisites for discovering new natural products, which involves the prospection of new biodiversity sources, which are often associated to new chemical/biological diversity. By using metagenomics, this project aims to explore soil microorganisms that are difficult to cultivate, which represents about 99% of the terrestrial microbiota. Metagenomic libraries from soil that belong to Laboratory of Microorganisms Chemistry of FCFRP-USP will be screened by fenotipic assay and antiparasitic assay against Leishmania major. By using interespecific interactions, it is expected that this approach will stimulate the biosynthesis of compounds that are coded in silent or underexpressed gene clusters in pure culture. Endophytic and soil actinobacteria will be cultured in pairs to allow interactions between different strains, and the search for promising pairs will be performed using yeast, gram-negative and gram-positive bacteria as bioactivity indicators to look for pairs that stimulate new bioactivities. After performing these screenings, the most promising interaction will be selected to characterize the bioactive compound and the compound that induces this new bioactivity, in order to try to describe the observed phenomenon. (AU)