ANTIBIOTIC DRUG DISCOVERY FROM MYXOBACTERIA

从粘细菌中发现抗生素药物

• 批准号: 8167817
• 负责人: DANIEL WALL
• 金额: $ 3.1万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167817
• 关键词: Address; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Bioinformatics; Biological Factors; Biology; Chemical Structure; Complex; Computer Retrieval of Information on Scientific Projects Database; Development; Fermentation; Funding; Gene Cluster; Genetic; Genome; Genomics; Goals; Grant; Hybrids; Institution; Medical; Myxococcales; Peptide Antibiotics; Predatory Behavior; Research; Research Personnel; Resources; Source; Testing; United States National Institutes of Health; Work; antibiotic TA; drug discovery; novel

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To address the growing problem of antibiotic resistance there is an important medical need to develop new antibacterials that work by novel mechanisms. This pilot proposal seeks to exploit myxobacteria as prolific producers of natural product antibiotics. Recent genomic and bioinformatic findings have highlighted this point as a stunning ~10 percent of myxobacterial genomes contain secondary metabolite biosynthetic gene clusters. This proposal seeks to tackle a central enigma of antibiotic drug discoverynamely, that natural products are the leading source of antibiotics, yet their development is hindered by low fermentation yields and complex chemical structures that make synthesis difficult. To address these problems, our first goal will be to test the feasibility of our hypothesis that the predatory behavior of myxobacteria can be exploited to genetically select optimized producer strains. A focus of these studies is on the natural product antibiotic TA; a promising novel hybrid polyketide-peptide antibiotic shown to be safe and have broad-spectrum antibacterial activity. Studies are aimed at understanding the genetic network involved in regulating ta expression and generating overproducer strains. A second goal is focused on elucidating the mode of action for antibiotic TA. The long term focus of this project is to develop the biology of myxobacteria as a source of therapeutically promising natural products.

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