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.
Claims15
A yeast cell for use in producing 3-hydroxypropionic acid (3-HP), wherein said yeast cell incorporates genetic modification such that said cell expresses the enzymes:
- Pyruvate decarboxylase (PDC)
- Aldehyde dehydrogenase (ALD)
- Acetyl-CoA synthase (ACS)
- Acetyl-CoA carboxylase (ACC*) mutated in at least one dephosphorylation site to prevent inactivation by Snf1
- Malonyl-CoA reductase (MCR),
- and has a reduced level of activity of NAD dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by virtue of deletion, attenuation, disruption, down-regulation, or mutation of one or more genes expressing NAD dependent GAPDH and 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, and
- 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.
A method for producing 3-HP, said method comprising culturing a yeast cells under conditions such that 3-HP is produced, wherein said yeast cell incorporates genetic modification such that said cell expresses the enzymes:
- Pyruvate decarboxylase (PDC)
- Aldehyde dehydrogenase (ALD)
- Acetyl-CoA synthase (ACS)
- Acetyl-CoA carboxylase (ACC*) mutated in at least one dephosphorylation site to prevent inactivation by Snf1
- Malonyl-CoA reductase (MCR), and has a reduced level of activity of NAD dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by virtue of deletion, attenuation, disruption, down-regulation, or mutation of one or more genes expressing NAD dependent GAPDH and has at least one exogenous gene encodin NADP dependent GAPDH and/or has up-regulation of at least one endogenous gene expressing NADP dependent GAPDH, and 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.
Dependencies are inferred from the claim text.