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Production of Farnesol and Geranylgeraniol
by Strains of Saccharomyces cerevisiae



Strains of S. cerevisiae were isolated from nitrous acid mutagenized cells that were specifically blocked in the isoprenoid/sterol biosynthetic pathway at the level of squalene synthase, coded by the ERG9 gene. These mutants also contained an additional mutation (or mutations) that allows for aerobic uptake of exogenous sterols. These erg9 mutants accumulate significant levels of farnesol, the prenyl alcohol derived from the isoprenoid/sterol pathway intermediate farnesyl pyrophosphate (FPP). When grown in fermentors under fed batch conditions, the cultures accumulated farnesol to approximately 2.5 g/L. HMG CoA reductase is an early enzyme of the isoprenoid/sterol pathway that is highly regulated to control the flux of carbon into this pathway. Over-expression of a de-regulated version of HMG CoA reductase was accomplished in the erg9 mutants by transforming these strains with a high copy number plasmid carrying the catalytic domain of the HMG2 gene. Farnesol accumulation increased to over 4 g/L when these strains were tested in fermentors. The Erwinia uredovora crtE gene coding for geranylgeranyl pyrophosphate synthase was over-expressed in these yeast mutants, which resulted in an elevation of geranylgeraniol accumulation. Surprisingly, similar results were obtained with strains that over-expressed the S. cerevisiae ERG20 gene, coding for FPP synthase.