Metabolic engineering of Saccharomyces cerevisiae for the production of taxa 4, 5-11, 12 diene

Production of many drugs and valuable chemicals is mainly obtained from plants. Among these valuable chemicals is taxol; a terpenoid which is an anticancer drug of high value but with low supply due to the low abundance in its natural host; Taxus sp. which makes it very difficult and extremely expensive to extract. Metabolic engineering is one of the techniques that is being researched to solve this problem through the production of the taxol in alternative hosts such as Saccharomyces cerevisiae and Escherichia coli which are easier hosts to modify due to the wealth of knowledge and tools available to genetically modify them. However, before the production of the taxol in the Saccharomyces cerevisiae it is important to produce its first known precursor; Taxa 4, 5-11, 12 diene (Taxadiene), abundant production of which can later be used to produce taxol. In this study the precursors to taxadiene were overproduced in Saccharomyces cerevisiae by boosting the mevalonate precursors; acetyl CoA, malonyl CoA & acetoacetyl CoA, and mevalonate through the integrated constructs which were expressed using strong constitutive promoters TEF1 and PGK1 . The performance of the Saccharomyces cerevisiae strains containing these constructs was tested with plasmids that had been used successfully to produce taxadiene in earlier research and significant increase of taxadiene of almost 30-fold were recorded.