Genomic engineering of biosynthetic pathways leading to increased NADPH
AssigneeZymergen Inc.
InventorsShawn Manchester, Benjamin Mason, Alexi Goranov
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Abstract
The disclosure relates to host cells having altered NADPH availability, allowing for increased production of compounds produced using NADPH, and methods of use thereof. NADPH availability is altered by one or more of: expressing an altered GAPDH, expressing a variant glutamate dehydrogenase (gdh), aspartate semialdehyde dehydrogenase (asd), dihydropicolinate reductase (dapB), and meso-diaminopimelate dehydrogenase (ddh), expressing a novel nicotinamide nucleotide transhydrogenase, expressing a novel threonine aldolase, and expressing or modulating the expression of a pyruvate carboxylase in the host cells.
Claims12
A method of improving a microbial cell's ability to produce L-lysine, the method comprising altering the microbial cell's available NADPH by genetically modifying the microbial cell to express:
- a) an aldehyde dehydrogenase from Lactobacillus agilis comprising SEQ ID NO:
- 30 or an aspartate-semi-aldehyde dehydrogenase from C. glutamicum comprising SEQ ID NO:40;
- b) an glutamate dehydrogenase from Clostridium symbiosum comprising SEQ ID NO:
- 44;
- c) a 4-hydroxy-tetrahydrodipicolinate reductase from Escherichia coli comprising SEQ ID NO:
- 48;
- and
- d) a meso-diaminopimelate D-dehydrogenase from C. glutamicum comprising SEQ ID NO:
- 4,
- wherein the microbial cell produces at least 40% more L-Lysine than a microbial cell that does not contain a)-d).
Dependencies are inferred from the claim text.