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 encoding a truncated yeast 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;
wherein the recombinant yeast has a decreased activity of squalene synthase relative to wild type yeast due to repression of an endogenous ERG9 gene by a heterologous repressible promoter
and wherein the recombinant yeast produces farnesyl or farnesol, in an amount greater than about 11% of dry cell weight.
2. The recombinant yeast of claim 1 , wherein the one or more heterologous nucleic acid molecules also encode a yeast enzyme that converts isopentenyl pyrophosphate to dimethylallyl pyrophosphate.
3. The recombinant yeast of claim 2 , wherein the one or more heterologous nucleic acid molecules also encodes a yeast enzyme that converts isopentenyl pyrophosphate and dimethylallyl pyrophosphate to farnesyl pyrophosphate.
4. The recombinant yeast of claim 3 , wherein the one or more heterologous nucleic acid molecules also encode a yeast enzyme that converts isopentenyl pyrophosphate and farnesyl pyrophosphate to geranylgeranyl pyrophosphate.
5. The recombinant yeast of claim 1 , wherein the one or more recombinant nucleic acid molecules are under inducible control.