Production of isoprenoids
View Patent ↗The invention provides a biological method of producing isoprenoids.
1. A recombinant yeast, comprising:
at least two integrated copies of a heterologous nucleic acid molecule encoding a truncated eukaryotic HMG-CoA reductase enzyme that converts hydroxymethylglutaryl-CoA to mevalonic acid; and
a plasmid comprising heterologous nucleic acid molecules encoding:
a yeast enzyme that converts mevalonic acid to phosphomevalonic acid;
a yeast enzyme that converts phosphomevalonic acid to phosphomevalonate; and,
a yeast enzyme that converts phosphomevalonate to isopentenyl pyrophosphate;
a eukaryotic enzyme that converts isopentenyl pyrophosphate and dimethylallyl pyrophosphate to farnesyl pyrophosphate;
wherein the recombinant yeast has a decreased activity of squalene synthase relative to wild type yeast due to a disruption of an endogenous ERG9 gene or due to a repression of an endogenous ERG9 gene by a heterologous repressible promoter,
and wherein the recombinant yeast produces farnesol or farnesol in an amount greater than about 11% of dry cell weight.
2. The recombinant yeast of claim 1 , wherein the decreased activity of squalene synthase relative to wild type yeast is due to a disruption of the endogenous ERG9 gene.
3. The recombinant yeast of claim 1 , wherein the heterologous nucleic acid molecules are under inducible control.
4. The recombinant yeast of claim 1 , wherein the truncated enzyme that converts hydroxymethylglutaryl-COA to mevalonic acid is a yeast enzyme.
5. The recombinant yeast of claim 1 , wherein each of the encoded enzymes is a yeast enzyme.