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US 10,480,015 B2Granted
Metabolic engineering for microbial production of terpenoid products
AssigneeManus Bio Inc.
InventorsAjikumar Parayil Kumaran, Ryan Lim, Jason Donald, Hsien-Chung Tseng, Christine Santos, Ryan Philippe
Life of this patent
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Abstract
The invention relates to methods and bacterial strains for making terpene and terpenoid products, the bacterial strains having improved carbon pull through the MEP pathway and to a downstream recombinant synthesis pathway.
Claims48
A method for production of a terpene or terpenoid product, comprising:
- providing an E. coli bacterial strain that produces isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) through an upstream methylerythritol phosphate pathway (MEP pathway) and converts the IPP and DMAPP to a terpene or terpenoid product through a recombinant downstream synthesis pathway;
- wherein IspG and IspH enzymes are overexpressed in the bacterial strain by complementation with recombinant ispG and ispH genes, such that IspH activity is higher than IspG activity to provide increased carbon flux to 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (HMBPP) intermediate, while preventing accumulation of HMBPP at an amount that feeds back and reduces MEP pathway flux and terpene or terpenoid productivity;
- the strain comprising a recombinant pyruvate:flavodoxin oxidoreductase (PFOR) enhancing supply and/or transfer of electrons through the MEP pathway and/or to terpene and terpenoid products, and culturing the bacterial strain to produce the terpene or terpenoid product.
A method for production of a terpene or terpenoid product, comprising:
- providing an E. coli bacterial strain that produces isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) through an upstream methylerythritol phosphate pathway (MEP pathway) and converts the IPP and DMAPP to a terpene or terpenoid product through a recombinant downstream synthesis pathway;
- wherein IspG and IspH enzymes are overexpressed in the bacterial strain by complementation with recombinant ispG and ispH genes, and the strain further comprises a recombinant pyruvate:flavodoxin oxidoreductase (PFOR), and
- culturing the bacterial strain to produce the terpene or terpenoid product.
Dependencies are inferred from the claim text.