Regulator-based genome mining for novel bioactive compounds in soil bacteria

PO-06 Regulator-based genome mining for novel bioactive compounds in soil bacteria Xu Cheng, Irene de Bruijn, Ester Dekkers, Menno van der Voort and Jos M. Raaijmakers Laboratory of Phytopathology, Wageningen University, the Netherlands; [email protected] Soil microorganisms represent an enormous resource for the discovery of novel genes and bioactive compounds, including antimicrobial metabolites and enzymes. Traditional methods to discover microbial products involve isolation and cultivation of a microorganism, followed by extraction, fractionation and structure elucidation of the bioactive compounds. The increase in the availability of microbial genomes has substantially changed our fundamental knowledge of the metabolic capabilities of microorganisms. Bioinformatics analyses of microbial genomes have revealed a large number of so-called orphan gene clusters, i.e. biosynthetic loci for which the corresponding pathways and metabolites are yet unknown. This study focuses on genome mining of Pseudomonas fluorescens strains for novel bioactive compounds and biosynthetic pathways. We adopted a targeted discovery strategy by generating mutations in two-component systems that act as global regulators of the production of secondary metabolites and exoenzymes in bacteria. A multidisciplinary approach involving activity bioassays, microarray-based expression profiling and genetic analyses resulted in the discovery of a new cluster of nonribosomal peptide synthetase genes that encode a putative novel compound with strong activities against fungal and oomycete pathogens.