3HP tolerance
AssigneeTechnical University of Denmark
InventorsKanchana Rueksomtawin Kildegaard, Irina Borodina, Jochen Förster, Jens Nielsen
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Abstract
Cells and cell cultures are provided that have improved tolerance to 3-hydroxypropionic acid (3HP). Genetic modifications to provide a mutated or overexpressed SFA1 gene or other enhancement of 3HP detoxification via a glutathione-dependent dehydrogenase reaction, including medium supplementation with glutathione, may be combined with a 3HP producing metabolic pathway.
Claims11
A cell having a metabolic pathway producing 3-hydroxypropionic acid (3HP), said cell exhibiting tolerance for 3HP and having one or more genetic modifications that provide for an enhanced activity of 3HP detoxification by a reaction pathway that includes a glutathione-dependent dehydrogenase reaction, wherein said one or more genetic modifications comprises one or more mutations in a gene′ encoding a glutathione-dependent formaldehyde dehydrogenase conferring tolerance for 3HP, and wherein the one or more mutations is at a position equivalent to the position aa276 Cys and/or at aa283 Met of the SFA1 gene of Saccharomyces cerevisiae.
A method of producing 3HP comprising cultivating a 3HP producing cell under 3HP producing conditions in a culture medium so as to produce 3HP, wherein toxicity of 3HP is reduced by an enhanced activity of 3HP detoxification by a reaction pathway that includes a glutathione-dependent dehydrogenase reaction, and wherein said culture medium is supplemented with glutathione.
A method of producing 3HP comprising cultivating a 3HP producing cell under 3HP producing conditions in a culture medium so as to produce 3HP, wherein toxicity of 3HP is reduced by an enhanced activity of 3HP detoxification by a reaction pathway that includes a glutathione-dependent dehydrogenase reaction, and wherein the cell overexpresses the glutathione biosynthetic genes gamma-glutamylcysteine synthetase and glutathione synthetase.
Dependencies are inferred from the claim text.