Collaborations in Chemistry: Putative Intermediates in the Biosynthesis of Tedanolide

化学合作：泰那内酯生物合成中的假定中间体

• 批准号: 0924351
• 负责人: Richard Taylor
• 金额: $ 45万
• 依托单位: University of Notre Dame
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0924351&HistoricalAwards=false
• 关键词: Collaborations; Chemistry; Putative; Intermediates; Biosynthesis

This project will investigate fundamental aspects of polyketide biosynthesis and evolution through a multidisciplinary collaboration. A synergistic synthetic effort, between the Richard Taylor group (University of Notre Dame) and the group of Professor Markus Kalesse (Leibniz Universitat Hannover), is directed at the putative intermediates in the biosynthesis of the marine polyketide, tedanolide. Putative biosynthetic intermediates, such as the targets of the current proposal, are a valuable new source of chemical diversity with the potential for discovery of novel biological targets and potentially new modes of action. In addition, the synthesis of iso-tedanolide will provide a unique opportunity to explore the feasibility of a 1,5-acyl migration, a key step in a proposed biogenic pathway to the tedanolides. Biological analyses will be carried out under the direction of Dr. Florenz Sasse at the Helmholtz Zentrum fuer Infektionsforschung (HZI Braunschweig). With this award, the Organic and Macromolecular Chemistry Program and the Office of International Science and Engineering are supporting the research of Professor Richard Taylor of the Department of Chemistry & Biochemistry at the University of Notre Dame. This award coordinates with a collaborative award funded by Deutsche Forschungsgemeinschaft (DFG) for Dr. Markus Kalesse, Leibniz Universitat Hannover and Dr. Florenz Sasse, Helmholtzzentrum für Infektionsforschung GmbH. Their research program involves the development of synthetic and biosynthetic methods for identification of new biologically active chemical entities inspired by the evolution of natural products and their producing organism. Successful preparation of these highly complex targets such as those proposed within this project will be enabled by the development of novel synthetic methods and strategies while providing a training platform for graduate and undergraduate student coworkers. Moreover, complementary biological studies of the prepared derivatives will probe the evolutionary role of post-polyketide synthase modifications in polyketide biosynthesis thus provide new information of fundamental significance.

这个项目将通过多学科合作研究聚酮生物合成和进化的基本方面。理查德·泰勒小组(圣母大学)和马库斯·卡莱斯教授小组(汉诺威莱布尼兹大学)之间的协同合成工作针对海洋聚酮--tedanolide生物合成中的假定中间体。假定的生物合成中间体，如当前提议的目标，是一种有价值的化学多样性的新来源，有可能发现新的生物目标和潜在的新的作用模式。此外，异萜内酯的合成将为探索1，5-酰基迁移的可行性提供一个独特的机会，而1，5-酰基迁移是合成萜内酯生物合成途径中的关键一步。生物分析将在Helmholtz Infektionsforschung(HZI Braunschweig)的Florenz Sasse博士的指导下进行。通过这一奖项，有机和高分子化学项目和国际科学与工程办公室支持圣母大学化学与生物化学系理查德·泰勒教授的研究。该奖项与德国金融研究基金会(DFG)为汉诺威莱布尼茨大学的Markus Kalesse博士和Helmholtzzentrum für Infektionsforschung GmbH的Florenz Sasse博士共同设立的奖项相协调。他们的研究计划包括开发合成和生物合成方法，以识别受天然产品及其生产有机体进化启发的新的生物活性化学实体。开发新的合成方法和战略，同时为研究生和本科生同事提供培训平台，将有助于成功准备这些高度复杂的目标，如本项目中提出的目标。此外，对所制备的衍生物的补充生物学研究将探索聚酮合酶后修饰在聚酮生物合成中的进化作用，从而提供具有基础意义的新信息。