S62: Identification of novel secondary metabolite biosynthetic clusters by genomic screening of immense strain collections

Warp Drive Bio’s mission is to identify novel natural products targeting the “undruggable genome”.  Prior genome sequencing studies have revealed a vast capability to produce secondary metabolites, far beyond that tapped by the pharmaceutical industry.  We are using a variety of genome scanning strategies to screen large Actinomycete strain collections for novel biosynthetic capabilities.  Actinomycetes present a number of challenges to current sequencing and bioinformatic technologies, given their large genome size (relative to many other bacteria), high degree of genomic variability, extremely high G+C content, the modular nature of secondary metabolite biosynthesis clusters and the frequent recombination and duplication in the evolution of these clusters.  Examples of novel secondary metabolite systems uncovered by these approaches will be presented, as well as technical and bioinformatic approaches to address the difficulties encountered in sequencing these genomes.