Compositions and methods for 3-hydroxypropionic acid production

{
  "publication_number": "US10260072B2",
  "country": "US",
  "kind": "B2",
  "title": "Compositions and methods for 3-hydroxypropionic acid production",
  "abstract": "The present application discloses genetically modified yeast cells comprising an active 3-HP fermentation pathway, and the use of these cells to produce 3-HP.",
  "claims": [
    "1. A genetically modified yeast cell comprising one or more 3-HP pathway genes selected from the group consisting of: an exogenous gene encoding an enzymatically active polypeptide that catalyzes the conversion of pyruvate to oxaloacetate (OAA); an exogenous gene encoding an enzymatically active polypeptide that catalyzes the conversion of aspartate to β-alanine; and an exogenous gene encoding an enzymatically active polypeptide that catalyzes the conversion of β-alanine to malonate semialdehyde and comprises at least 85% sequence identity to an amino acid sequence from SEQ ID NO: 20, 21, or 24.",
    "2. The genetically modified yeast cell of claim 1, wherein the yeast cell is selected from a Crabtree-negative yeast, an Issatchenkia yeast, a Candida yeast, a Kluyveromyces yeast, a Pichia yeast, a Schizosaccharomyces yeast, a Torulaspora yeast, a Zygosaccharomyces yeast, or a Saccharomyces yeast.",
    "3. The genetically modified yeast cell of claim 2, wherein the yeast cell is selected from the group consisting of Issatchenkia orientalis, Candida lambica, and Saccharomyces bulderi.",
    "4. The genetically modified yeast cell of claim 1, wherein the exogenous gene encoding the enzymatically active polypeptide that catalyzes the conversion of aspartate to β-alanine comprises an aspartate decarboxylase (ADC) gene that encodes a polypeptide with at least 50% sequence identity to an amino acid sequence from SEQ ID NO: 17, 18, 133, 135, 137, or 139.",
    "5. The genetically modified yeast cell of claim 1, wherein the genetically modified yeast cell further comprises an exogenous gene encoding an enzymatically active polypeptide that catalyzes the conversion of oxaloacetate (OAA) to aspartate.",
    "6. The genetically modified yeast cell of claim 5, wherein the exogenous gene encoding the enzymatically active polypeptide that catalyzes the conversion of oxaloacetate (OAA) to aspartate comprises an aspartate aminotransferase AAT gene that encodes a polypeptide with at least 50% sequence identity to an amino acid sequence from SEQ ID NO: 14, 15, or 16.",
    "7. The genetically modified yeast cell of claim 1, wherein the exogenous gene encoding the enzymatically active polypeptide that catalyzes the conversion of pyruvate to oxaloacetate (OAA) comprises an pyruvate carboxylase gene PYC gene that encodes a polypeptide with at least 50% sequence identity to an amino acid sequence from SEQ ID NO: 2, 3, 4, 5, 6, 7, or 8.",
    "8. The genetically modified yeast cell of claim 1, wherein the genetically modified yeast cell further comprises an exogenous gene encoding an enzymatically active polypeptide that catalyzes the conversion of phosphoenoylpyruvate (PEP) to oxaloacetate (OAA).",
    "9. The genetically modified yeast cell of claim 8, wherein the exogenous gene encoding the enzymatically active polypeptide that catalyzes the conversion of phosphoenoylpyruvate (PEP) to oxaloacetate (OAA) comprises an PEP carboxylase gene (PCK) that encodes a polypeptide comprising an amino acid sequence from SEQ ID NO: 35, 36, 37, 38, or 39.",
    "10. The genetically modified yeast cell of claim 1, wherein the genetically modified yeast cell further comprises a deletion or disruption of one or more native genes involved in ethanol fermentation.",
    "11. The genetically modified yeast cell of claim 10, wherein the one or more native genes involved in ethanol fermentation comprises pyruvate decarboxylase (PDC) or alcohol dehydrogenase (ADH).",
    "12. The genetically modified yeast cell of claim 1, wherein the genetically modified yeast cell further comprises a deletion or disruption of one or more native genes encoding glycerol 3-phosphate dehydrogenase (GPD), glycerol 3-phosphatase (GPP), glycerol kinase, dihydroxyacetone kinase, glycerol dehydrogenase, aldehyde dehydrogenase (ALD), or butanediol dehydrogenase."
  ],
  "description_excerpt": "3-hydroxypropionic acid (3-HP) is a three carbon carboxylic acid identified by the U.S. Department of Energy as one of the top 12 high-potential building block chemicals that can be made by fermentation. Alternative names for 3-HP, which is an isomer of lactic (2-hydroxypropionic) acid, include ethylene lactic acid and 3-hydroxypropionate. 3-HP is an attractive renewable platform chemical, with 100% theoretical yield from glucose, multiple functional groups that allow it to participate in a variety of chemical reactions, and low toxicity. 3-HP can be used as a substrate to form several commodity chemicals, such as 1,3-propanediol, malonic acid, acrylamide, and acrylic acid. Acrylic acid is a large-volume chemical (>7 billion lbs/year) used to make acrylate esters and superabsorbent polymers, and is currently derived from catalytic oxidation of propylene. Fermentative production of 3-HP would provide a sustainable alternative to petrochemicals as the feedstock for these commercially-significant chemicals, thus reducing energy consumption, US dependence on foreign oil, and the production of greenhouse gases.\n\nBacteria can be used to ferment sugars to organic acids. However, bacteria present certain drawbacks for large-scale organic acid production. As organic acids are produced, the fermentation medium becomes increasingly acidic. Lower pH conditions are actually preferable, because the resultant product is partially or wholly in the acid form.",
  "cpc": [
    "C12N 15/52",
    "C12N 1/18",
    "C12N 15/81",
    "C12N 15/815",
    "C12N 9/0006",
    "C12N 9/1096",
    "C12N 9/88",
    "C12N 9/93",
    "C12P 7/42",
    "C12P 7/52",
    "C12Y 101/01059",
    "C12Y 206/01001",
    "C12Y 206/01018",
    "C12Y 206/01019",
    "C12Y 401/01031"
  ],
  "ipc": [
    "C12N 1/18",
    "C12N 15/52",
    "C12N 15/81",
    "C12N 9/00",
    "C12N 9/04",
    "C12N 9/10",
    "C12N 9/88",
    "C12P 7/42",
    "C12N 1/14"
  ],
  "assignees": [
    "Cargill Inc"
  ],
  "inventors": [
    "Holly Jessen",
    "Brian Rush",
    "Jeanette Huryta",
    "Beth Mastel",
    "Alan Berry",
    "Debbie Yaver",
    "Michael Catlett",
    "Michelle Barnhart"
  ],
  "filing_date": "2017-08-28",
  "publication_date": "2019-04-16",
  "grant_date": "2019-04-16",
  "priority_date": "2010-11-22",
  "application_number": "US-201715688436-A",
  "family_id": "45099210",
  "cited_by_count": 11,
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