Expression Enhanced Natural Product Pathways Using Advanced Metagenomic Tools

使用先进的宏基因组工具表达增强的天然产物途径

基本信息

批准号：
9025682
负责人：
Scott Allen Monsma
金额：
$ 34.84万
依托单位：
LUCIGEN CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-03-01 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9025682
关键词：
Address Anabolism Anti-Bacterial Agents Anti-Infective Agents Antibiotics Antifungal Agents Bacterial Artificial Chromosomes Biological Assay Buffaloes Centers for Disease Control and Prevention (U.S.)Chemicals Chemistry Clinical Cloning Collection Complex DNA Data Engineering Environment Escherichia coli Gene Expression Genes Genetic Genomics Goals Growth Health High-Throughput Nucleotide Sequencing Lead Libraries Marketing Measurable Metagenomics Methods Microbe Multi-Drug Resistance Natural Product Drug Natural Products Outcome Outcomes Research Pathway interactions Patients Personal Satisfaction Procedures Process Production Property Reporting Sequence Analysis Series Source Technology Therapeutic Therapeutic Agents Time Translations Viral antimicrobial base cellular engineering cost design drug discovery drug resistant bacteria improved innovative technologies interest large scale production microbial next generation novel pathogen screening small molecule small molecule therapeutics success tool

项目摘要

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.

描述（由申请人提供）：多重耐药性的后抗生素时代已经开始威胁人类的健康和福祉，将未开发的天然产品潜力经济地转化为最终可规模化生产的一个关键限制是缺乏下一代。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，从而产生了一系列有效的新型环境衍生产品。有两种独特的成分可实现这一目标：1) 一种新的工程大肠杆菌菌株，可支持天然产物生物合成途径表达所需的许多独特构建模块；2) 包含 800 个克隆的 BAC 文库。长达 170 kb 的完整小分子途径可表达针对 ESKAPE 系列病原体的抗菌活性。这项研究的结果预计将显着加速新型药物的发现和生产。抗菌化合物。