There is a growing class of natural products, the ribosomally synthesized and post-translationally modified peptides (RiPPs) that are ideally suited to the generation and screening of peptide libraries. RiPPs are synthesized from a genetically encoded precursor peptide. The ability to synthesize large libraries of precursor peptide encoding genes through chemical DNA synthesis, allows for the generation of large libraries of natural product-like cyclic peptides. Furthermore, because the precursor peptides are genetically encoded, technologies that have been developed for the directed evolution of proteins can be leveraged for screening these compounds.
Species of Lysobacter have been identified in disease suppressive soils, and a number of natural products produced by this genus have been characterized, including potent antibiotics. Nonetheless, genome sequences reveal a large number of biosynthetic pathways whose product have not been characterized. Through genome sequencing, bioinformatic analysis, and traditional activity guided screening, we will identify new antibiotic compounds produced by these organisms.