P57: Discovery of a pantothenate (vitamin B5) dependent metabolic switch in farnesene producing Saccharomyces cerevisiae

Nutrient deficiencies in cell culture media are often thought to be an undesirable feature in the strain improvement process.  However, we have discovered that limiting the availability of the common media vitamin pantothenate can be used to increase the genetic stability of recombinant Saccharomyces cerevisiae producing high levels of farnesene.  Although, S. cerevisiae has been demonstrated to have a functional pantothenate synthesis pathway, it is not active enough to support the maximal growth rate on glucose or sucrose carbon sources and some lab strains may be pantothenate or beta-alanine auxotrophs.  We take advantage of this fact by eliminating or reducing the media availability of pantothenate to reduce the intracellular concentration of coenzyme A and acetyl-CoA, thereby reducing the flux to farnesene with little to no impact on the maximal growth rate of the farnesene producer and a much improved biomass yield. We will present a comprehensive ‘omics data set to aid the interpretation of this result and describe the application of this “metabolic” switch to improving strain stability during the engineering and scale up of high yielding farnesene producing yeast strains.