Collaborations in Chemistry: Putative Intermediates in the Biosynthesis of Tedanolide

University Of Notre Dame, Notre Dame IN

Investigators

Abstract

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.