CAREER: Chemoenzymatic Total Synthesis of Terpenoids via P450 Catalysis

With this Award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Hans Renata in the Department of Chemistry at The Scripps Research Institute. This research develops new strategies for the synthesis of terpenoids, naturally occurring small molecules that have a variety of biological functions. Many of these terpenoid molecules can only be obtained in small quantities from natural sources. Laboratory methods to prepare them in an efficient manner still remain an unsolved challenge. The research uses nature’s catalysts, i.e. enzymes, to modify starting materials and produce useful building blocks. The building blocks are then used to prepare a wide range of terpenoids. Streamlined access to terpenoids enabled by this research strategies helps support further studies on their physiological functions. Students working on these studies receive important training in chemical and biological sciences to support their future careers in science and engineering. Concomitant with the research activities, the Professor Renata is organizing outreach efforts including classroom education and public engagement to cultivate interest in science among young students and members of the local community. The Renata lab aims to develop novel strategies to access important natural products by incorporating biocatalytic transformations. The goal of this project is to establish chemoenzymatic means to access oxidized terpenoids with unique structural motifs, specifically terpenoids bearing “trans-trans-trans”, “trans-trans-syn” and “trans-syn-trans” ring junctions. This is achieved by combining site-selective biocatalytic oxidation of readily available feedstock terpenes and state-of-the-art chemical methodologies for carbon-carbon bond constructions. Studies in this area help formulate a new type of synthetic logic (“chemoenzymatic logic”) for accessing complex molecules with interesting architectures. To complement the research activities, outreach efforts, new coursework material in biocatalysis, and an external lecture series are designed to encourage participation in science among young students, underrepresented groups and members of the local community. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.