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

• 批准号: 8903016
• 负责人: DAVID Alan MEAD
• 金额: $ 35万
• 依托单位: LUCIGEN CORPORATION
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8903016
• 关键词: Address; Anabolism; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics; Antifungal Agents; Biological Assay; Biological Factors; 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; 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; public health relevance; screening; small molecule; success; tool

 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.