BAC Sudoku Sequencing Paradigm to Accelerate Metagenomic Natural Product Chemistr

DESCRIPTION (provided by applicant): There is societal need for new compounds in our arsenal of defenses against microbial pathogens, many of which are increasingly resistant to existing therapeutics. The best possible source for new antimicrobial compounds with potentially novel mechanisms of action is within natural environments, particularly soils, which have the greatest diversity of microbial life. This research proposal advances the science of metagenomics, the cloning of DNA from entire microbial communities, to discover novel antibiotics and identify the best lead candidates for clinical development. Scientists at Lucigen Corporation and Auburn University have combined key technological breakthroughs that result in an improved paradigm for screeningmetagenomic libraries for small molecules. A major rate limiting step in this process is the millions of bioassays required to screen natural product libraries for small molecules with bioactivity. This Phase I SBIR will develop new tools for massivel