- Using chemical mutagenesis and screening, strains of
S. cerevisiae were isolated that carry a mutation
in the erg9 gene as well as another gene (or
genes) that confer aerobic sterol uptake. When grown
under fed-batch conditions in fermentors, these strains
accumulated more than 2.5 g/L farnesol.
- Amplification of either GGPP synthase or FPP synthase
in erg9 mutants led to the elevated accumulation
of GGOH, but the major isoprenoid produced by these
strains was farnesol.
- Amplification of de-regulated HMG CoA reductase
activity in erg9 mutants led to higher
accumulation of farnesol, but this was only seen when the
cells were cultured in fermentors under fed-batch
conditions. These strains have been shown to accumulate
over 4 g/L farnesol.
- Amplification of the first three steps in the
isoprenoid pathway, namely acetoacetyl CoA thiolase, HMG
CoA synthase, and deregulated HMG CoA reductase, led to a
significant increase in mevalonate accumulation, but
farnesol levels were not affected, suggesting a metabolic
restriction at the level of mevalonate kinase.
