Metabolic engineering for microbial production of terpenoid products
AssigneeManus Bio Inc.
InventorsAjikumar Parayil Kumaran, Ryan Lim, Jason Donald, Hsien-Chung Tseng, Christine Nicole S. Santos, Ryan Philippe
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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.
Claims27
A bacterial strain having one or more genetic modifications that increase production of products from isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) precursors;
- the bacterial strain producing isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) through an methylerythritol phosphate pathway (MEP pathway), and the MEP pathway comprising one or more overexpressed genes;
- the strain converting the IPP and DMAPP to a terpene or terpenoid product through a downstream synthesis pathway;
- wherein said genetic modifications comprise:
- (a) recombinant or modified IspG and IspH enzymes, the IspG and IspH enzymes having balanced expression or activity to prevent accumulation of (1-hydroxy-2-methyl-2(E)-butenyl 4-diphosphate (HMBPP) intermediate,
- (b) a recombinant or modified gene encoding an enzyme that enhances supply and/or transfer of electrons through the MEP pathway and/or to terpene or terpenoid products, and
- (c) an inactivation or deletion, or reduced expression or activity, of aceE or aceE enzyme complex.
The bacterial strain of 15, further comprising an overexpression of one or more of a flavodoxin, flavodoxin reductase, ferredoxin, and ferredoxin reductase.
Dependencies are inferred from the claim text.