Expression Enhanced Natural Product Pathways Using Advanced Metagenomic Tools

 描述(申请人提供)：后抗生素时代的多重耐药已经开始威胁人类的健康和福祉。在从经济上将未开发的自然产品潜力转化为最终可扩展生产方面的一个关键限制是缺乏下一代工具来有效地获得自然环境的全部医疗影响。该项目利用创新技术捕获整个小分子途径，并首次在大肠杆菌中表达它们，从而形成了一条有效的新型环境衍生管道。 治疗性化合物。有两个独特的组件可用于实现这一目标：1)新的工程大肠杆菌菌株，支持表达天然产物生物合成途径所需的许多独特的构建块；2)800个克隆的BAC文库，包含长达170 kb的完整小分子途径，用于检测对ESKAPE系列病原体的抗菌活性。预计这项研究的结果将大大加快新型抗菌化合物的发现和生产。

 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: 1) A new strain of engineered E. coli to support many of the unique building blocks needed for expression of natural product biosynthetic pathways and 2) A BAC library of 800 clones containing entire small molecule pathways up to 170 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.