Metabolic engineering of the ergosterol pathway of Saccharomyces cerevisiae to improve production of the triterpene friedelin

Abstract

Friedelin is a pentacyclic triterpene found in the leaves of some plant species, such as Maytenus ilicifolia. This compound is itself biologically active and is also a precursor of triterpene quinone methides tingenone and pristimerin, which are important anti-inflammatory agents and promising in the treatment of several cancer types. However they are produced only in the root bark of the young plant, which hampers its obtainment. Starting from the oxidosqualene molecule, different pathways lead to the production of sterois of plant, fungus and mammal membranes, hormones in plants and animals or secondary terpenic derivatives, as the triterpenes like friedelin. The friedelin synthase from the leaves of M. ilicifolia was cloned and its functionally was characterized by expression in Saccharomyces cerevisiae (Fapesp Process 2011/10379-1). The objective of this project is to modify genetically the yeast S. cerevisiae to improve the production of friedelin synthase already cloned from M. ilicifolia. The project is designed to be developed in the Chalmers University of Technology (Göteborg, Sweden), in the group of Professor Jens Nielsen which has the expertise in optimizing genetic modifications in yeast in order to achieve higher production of important biotechnological compounds. His research groups has been developing yeast models able to function as sustainable factories of high value chemicals such as isoprenoids, polymers and advanced biofuels. So that, the project will analyze and modify genes of S. cerevisiae by Synthetic Biology techniques allied to omic tools to express the cloned gene of friedelin synthase in the modified strains and assess the production of friedelin by chromatographic methods, examining yeast mutations that may result in better friedelin production profiles. (AU)