Microbial production of 3-hydroxypropionic acid
AssigneeTechnical University of Denmark
InventorsNiels Bjerg Jensen, Irina Borodina, Yun Chen, Jerome Maury, Kanchana Rueksomtawin Kildegaard, Jochen Förster, Jens Nielsen
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Abstract
A yeast cell having a reduced level of activity of NAD dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has at least one exogenous gene encoding NADP dependent GAPDH and/or has up-regulation of at least one endogenous gene expressing NADP dependent GAPDH, wherein combined expression of the enzymes NADP dependent GAPDH, PDC, ALD, ACS, ACC* and MCR in said host cell increases metabolic flux towards 3-HP via malonyl-CoA compared to an otherwise similar yeast cell lacking said genetic modification.
Claims14
A genetically modified yeast cell for use in producing 3-hydroxypropionic acid (3-HP), wherein said yeast cell expresses the enzymes:
- Pyruvate decarboxylase (PDC),
- Aldehyde dehydrogenase (ALD),
- Acetyl-CoA synthase (ACS),
- Acetyl-CoA carboxylase (ACC*), wherein the ACC* is yeast acetyl-CoA carboxylase mutated in at least one phosphorylation site to prevent inactivation by yeast sucrose non-fermenting 1 (Snf1), and
- Malonyl-CoA reductase (MCR),
- wherein the yeast cell has a reduced level of activity of NAD-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by deletion or disruption of one or more genes encoding a NAD-dependent GAPDH,
- wherein the yeast cell has been transformed with at least one exogenous nucleic acid molecule encoding a NADP-dependent GAPDH, and
- wherein culturing said yeast cell expressing the enzymes NADP-dependent GAPDH, PDC, ALD, ACS, ACC* and MCR on a medium comprising at least one carbon substrate produces a supernatant concentration of at least 9 g/L 3-HP.
Dependencies are inferred from the claim text.