Genome-mining for exploration of new insecticidal compounds produced by insect-associated bacterial symbionts

Abstract

Microorganisms present the ability to produce numerous biologically active compounds of proven value to human and veterinary medicine and agriculture. The use of microorganisms isolated in unexplored niches stands out as a promising strategy for the identification of new metabolites. One of such niches is represented by insect-associated bacterial symbionts. Due to difficulties in the isolation and cultivation of insect-associated bacterial symbionts, these microorganisms are often neglected. Nevertheless, our previous studies in which classical tools for cultivation and extraction of molecules were applied allowed us to prove the potential application of these microorganisms. But exploration of the full potential of such microorganisms has been limited by our capacity to induce the expression of the full repertoire of genes involved in the synthesis of secondary metabolites. Therefore, the use of modern tools of molecular biology and bioinformatics in order to access silent biosynthetic pathways is key to enhance our potential to efficiently explore the full biotechnological potential of these microorganisms. We have employed tools to allow for the identification and characterization of biosynthetic gene clusters to elucidate the biosynthesis of secondary metabolites in one of our model symbiont, and demonstrated identified cryptic metabolites encoded by silent biosynthetic pathways that remain to be identified. But the identification of such cryptic metabolites requires specific chemical knowledge on predictive synthesis and the use of particular techniques for the expression of genes of interest and synthesis of molecules, which we are not trained for yet. Thus, for the successful development of the current project, we propose to develop this part of the project in collaboration and under the supervision of Professor Dr. Jörn Piel, from the Bacterial Natural Products Lab, Department of Biology, Institute of Microbiology, ETH Zurich. (AU)