Engineering a Functional Deoxyxylulose Phosphate (DXP) Pathway in Saccharomyces Cerevisiae

Isoprenoids and their chemical derivatives are used in many commercial and industrial products. Producing these compounds via the engineering of microbial systems is an attractive alternative to extraction from their native source because it can provide a more sustainable source, a more stable supply, and/or lower production costs.  All isoprenoids are formed from the two activated hydrocarbon monomers isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP).  Depending on the organism, these monomers are either produced from acetyl-CoA by using the mevalonate pathway or from pyruvate and glyceraldehyde-3-phosphate by using the deoxyxylulose phosphate (DXP) pathway.  The baker’s yeast Saccharomyces cerevisiae exclusively utilizes the mevalonate pathway.  In this work, we describe the use of synthetic biology, proteomics, in vitro biochemistry and metabolomics to engineer a functional heterologous DXP pathway in Saccharomyces cerevisiae and demonstrate the biosynthesis of IPP and DMAPP through the DXP pathway in yeast.