Expression Enhanced Natural Product Pathways Using Advanced Metagenomic Tools

DESCRIPTION provided by applicant A post antibiotic era of multiple drug resistance has begun to threaten the health and well being of mankind A crucial limitation in economically converting untapped natural product potential to final scalable production is the lack of next generation tools to effectively access the full medicinal impact of natural environments This project utilizes innovative technologies to capture entire small molecule pathways and express them for the first time in E coli resulting in a potent pipeline of novel environmentally derived therapeutic compounds There are two unique components available to achieve this goal A new strain of engineered E coli to support many of the unique building blocks needed for expression of natural product biosynthetic pathways and A BAC library of clones containing entire small molecule pathways up to kb to be assayed for expression of anti bacterial activities against the ESKAPE series of pathogens The outcomes of this research are expected to significantly accelerate the discovery and production of novel antimicrobial compounds PUBLIC HEALTH RELEVANCE This proposal is designed to accelerate the expression and discovery of environmentally encoded complex natural products Success will provide new antimicrobial compounds with the potential for more efficient economical rapid and effective clinical translation and large scale production