ANTIBIOTIC DRUG DISCOVERY FROM MYXOBACTERIA

从粘细菌中发现抗生素药物

• 批准号: 8359736
• 负责人: DANIEL WALL
• 金额: $ 3.42万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8359736
• 关键词: Address; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Bioinformatics; Biological Factors; Biology; Biomedical Research; Chemical Structure; Complex; Development; Fermentation; Funding; Gene Cluster; Genetic; Genome; Genomics; Goals; Grant; Hybrids; Medical; Myxococcales; National Center for Research Resources; Peptide Antibiotics; Predatory Behavior; Principal Investigator; Research; Research Infrastructure; Resources; Source; Testing; United States National Institutes of Health; Work; Wyoming; antibiotic TA; cost; drug discovery; novel

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. TTo 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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 TTO解决了日益增长的抗生素耐药性问题，有重要的医学需要开发通过新型机制起作用的新抗菌物质。 该试点建议旨在利用粘霉菌作为天然产品抗生素的多产者。 最近的基因组和生物信息学发现强调了这一点，因为令人惊叹的〜10％的粘细菌基因组含有次级代谢物生物合成基因簇。 该提案旨在应对发现抗生素药物的中心谜团，即天然产物是抗生素的主要来源，但它们的发育受到低发酵产量和使合成困难的复杂化学结构的阻碍。 为了解决这些问题，我们的第一个目标是测试我们假设的可行性，即可以利用粘霉菌的掠食性行为来利用遗传选择的优化生产者菌株。 这些研究的重点是天然产物抗生素TA。一种有前途的新型杂化聚酮化合物肽抗生素，表现为安全，具有广谱抗菌活性。 研究旨在了解调节TA表达和产生过度生产菌株的遗传网络。 第二个目标是阐明抗生素TA的作用方式。 该项目的长期重点是发展粘霉菌的生物学，作为治疗有前途的天然产品的来源。