Antibiotics are an essential component in bio-defense preparedness. Soil microorganisms were a major source of antibiotics during the 20th century, yet antibiotic discovery is now severely limited. A primary reason is that drug discovery from microorganisms has been confined to those microbes that can be recovered by laboratory cultivation, yielding high rates of antibiotic rediscovery. eMetagen's pioneering technology for the direct cloning of microbial genomic DNA from soils will be used to discover new antibiotics targeting NIAID category A and B bio-defense pathogens. Antibiotic biosynthesis pathways typically contain many genes therefore eMetagen's technology for cloning large DNA fragments is critical for antibiotic discovery. Innovative approaches will be used for the construction of large-genomic-DNA-insert libraries (Aim 1) that will be screened in an array format for genes encoding new polyketide antibiotics (Aim 2). eMetagen libraries will also be screened for new classes of broad spectrum antibiotics with activity against bioweapon surrogates (Aim 3). Intellectual property will include the improved eMetagen libraries, the arrayed libraries, the chemical structures of discovered antibiotics and the genes encoding their synthesis. In Phase II, eMetagen will fully characterize polyketide and other antibiotics discovered in Phase I and partner with pharmaceutical companies and government laboratories to advance product development.
