Genetically modified host cells and use of same for producing isoprenoid compounds
AssigneeThe Regents of the University of California
InventorsJay D. Keasling, James Kirby, Eric M. Paradise
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Abstract
The present invention provides genetically modified eukaryotic host cells that produce isoprenoid precursors or isoprenoid compounds. A subject genetically modified host cell comprises increased activity levels of one or more of mevalonate pathway enzymes, increased levels of prenyltransferase activity, and decreased levels of squalene synthase activity. Methods are provided for the production of an isoprenoid compound or an isoprenoid precursor in a subject genetically modified eukaryotic host cell. The methods generally involve culturing a subject genetically modified host cell under conditions that promote production of high levels of an isoprenoid or isoprenoid precursor compound.
Claims30
A genetically modified eukaryotic host cell that produces an isoprenoid or an isoprenoid precursor compound via a mevalonate pathway, the genetically modified eukaryotic host cell comprising genetic modifications comprising:
- a) a heterologous nucleic acid, integrated into the host cell's chromosome, encoding an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) to mevalonate;
- b) a heterologous nucleic acid, integrated into the host cell's chromosome, encoding farnesyl diphosphate (FPP) synthase,
- c) a heterologous nucleic acid, integrated into the host cell's chromosome, to decrease the level of activity of squalene synthase;
- and
- d) a heterologous nucleic acid comprising a nucleotide sequence encoding a terpene synthase,
- wherein the genetic modifications provide for production of an isoprenoid or an isoprenoid precursor compound at a level that is at least about 50% higher than the level of the isoprenoid or isoprenoid precursor compound in a control cell not comprising the genetic modifications.
Dependencies are inferred from the claim text.