Biological production of novel organofluorines via terpene biosynthesis and S.cerevisiae engineering

Objective

Fluorine offers unique properties that are invaluable in molecular design and discovery. Its importance is evidenced by the overrepresentation of fluorine among synthetic small molecule therapeutics. However, unlike synthetic chemists, nature rarely uses fluorine as part of its design tools to construct bioactive molecules. To introduce fluorine into complex scaffolds such as natural products would offer enormous potential for accessing new structural space that combine beneficial features of biological and synthetic molecules for the discovery of novel functions. This proposal, Bio-fluorine, aims to explore the incorporation of fluorine into terpenoids, which constitute the largest and most diverse class of natural products, using biosynthetic enzymes. The proposed research seeks to develop an entirely enzymatic pathway to incorporate fluorine from a simple precursor into diverse carbon skeletons. The proposed work also aims to develop a Saccharomyces cerevisiae chassis for scalable biological fluorine incorporation and novel organofluorine production.