Production of taxol precursors with yeast cell factories

Taxol is an important anticancer agent that is naturally produced by plant. As the plants yield is not consistent and is subjected to fluctuations, the need for another source became a must to make the production process more economical and consistent. Many isoprenoid compounds have been successfully produced in S. cerevesiae and reached good yields through modifying the mevalonate pathway by metabolic engineering tools. Taxol, in the same way, can be produced in Saccharomyces cerevesiae. Taxadiene is a precursor to Taxol and there have been many attempts to increase its yield in yeast through engineering the mevalonate pathway. In this study, in order to increase taxadiene yield in S. cerevesiae, farnesyl diphosphate synthase (ERG20), taxadeine synthase (TS) and geranyl geranyl diphosphate synthase (GGPPS) genes were introduced into S. cerevesiae via episomal plasmids. Effect of GGPSS genes from four different strains; Taxus canadensis, Sulfolobus acidophilus, Taxus baccata, and Taxus cuspidata was investigated to select best GGPPS gene for producion of taxadiene in S. cerevesiae. In comparison to the to the reference strain Taxadiene production increased by 31 folds by strain contained overexpressed GGPPS gene from Sulfolobus acidophilus, ERG20 and TS genes.