Monofunctional aldehyde and alcohol dehydrogenases for production of fuels and commodity chemicals
AssigneesThe Regents of the University of California, Calysta, Inc.
InventorsMichelle C.Y. CHANG, Matthew DAVIS, Josh SILVERMAN, Drew REGITSKY
Life of this patent
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Abstract
The present disclosure relates generally to the production of alcohols, and more specifically to biological platforms for the production of alcohols using monofunctional aldehyde dehydrogenases and monofunctional alcohol dehydrogenases.
Claims36
A recombinant host cell that facilitates the production of an alcohol from an acyl-CoA, wherein the host cell comprises:
- a) a first nucleic acid which encodes a polypeptide involved in the stepwise conversion of an acyl-CoA to a substrate for a monofunctional aldehyde dehydrogenase;
- b) a second nucleic acid which encodes a monofunctional aldehyde dehydrogenase;
- and
- c) a third nucleic acid which encodes a monofunctional alcohol dehydrogenase;
- wherein at least one nucleic acid selected from the group consisting of the first nucleic acid, the second nucleic acid, and the third nucleic acid is a recombinant nucleic acid.
A recombinant host cell for the production of n-butanol, the host cell comprising:
- a) a nucleic acid encoding an acetoacetyl-CoA thiolase capable of catalyzing the conversion of acetyl-CoA to acetoacetyl-CoA;
- b) a nucleic acid encoding a 3-hydroxybutyryl-CoA dehydrogenase capable of catalyzing the conversion of acetoacetyl-CoA to 3-hydroxybutyryl-CoA;
- c) a nucleic acid encoding a crotonase capable of catalyzing the conversion of 3-hydroxybutyryl-CoA to crotonyl-CoA;
- d) a nucleic acid encoding a trans-enoyl-CoA reductase capable of catalyzing the conversion of crotonyl-CoA to butyryl-CoA;
- e) a nucleic acid encoding a monofunctional aldehyde dehydrogenase capable of catalyzing the conversion of butyryl-CoA to butyraldehyde;
- f) a nucleic acid encoding a monofunctional alcohol dehydrogenase capable of catalyzing the conversion of butyraldehyde to n-butanol;
- wherein one or more of the nucleic acids are recombinant, and wherein the host cell is capable of producing at least 10-fold more n-butanol than ethanol.
A recombinant host cell for the production of crotyl alcohol, the host cell comprising:
- a) a nucleic acid encoding an acetoacetyl-CoA thiolase capable of catalyzing the conversion of acetyl-CoA to acetoacetyl-CoA;
- b) a nucleic acid encoding a 3-hydroxybutyryl-CoA dehydrogenase capable of catalyzing the conversion of acetoacetyl-CoA to 3-hydroxybutyryl-CoA;
- c) a nucleic acid encoding a crotonase capable of catalyzing the conversion of 3-hydroxybutyryl-CoA to crotonyl-CoA;
- d) a nucleic acid encoding a monofunctional aldehyde dehydrogenase capable of catalyzing the conversion of crotonyl-CoA to crotonaldehyde;
- e) a nucleic acid encoding a monofunctional alcohol dehydrogenase capable of catalyzing the conversion of crotonaldehyde to crotyl alcohol;
- wherein one or more of the nucleic acids are recombinant.
A recombinant host cell for the production of 1,3-butanediol, the host cell comprising:
- a) a nucleic acid encoding an acetoacetyl-CoA thiolase capable of catalyzing the conversion of acetyl-CoA to acetoacetyl-CoA;
- b) a nucleic acid encoding a 3-hydroxybutyryl-CoA dehydrogenase capable of catalyzing the conversion of acetoacetyl-CoA to 3-hydroxybutyryl-CoA;
- c) a nucleic acid encoding a monofunctional aldehyde dehydrogenase capable of catalyzing the conversion of 3-hydroxybutyryl-CoA to 3-hydroxybutyraldehyde;
- d) a nucleic acid encoding a monofunctional alcohol dehydrogenase capable of catalyzing the conversion of 3-hydroxybutyraldehyde to 1,3-butanediol;
- wherein one or more of the nucleic acids are recombinant.
A recombinant host cell for the production of 4-hydroxy-2-butanone, the host cell comprising:
- a) a nucleic acid encoding an acetoacetyl-CoA thiolase capable of catalyzing the conversion of acetyl-CoA to acetoacetyl-CoA;
- b) a nucleic acid encoding a monofunctional aldehyde dehydrogenase;
- c) a nucleic acid encoding a monofunctional alcohol dehydrogenase;
- wherein one or more of the nucleic acids are recombinant.
A recombinant host cell for the production of one or more C4 alcohols, the host cell comprising:
- a) a nucleic acid encoding an acetoacetyl-CoA thiolase;
- b) a nucleic acid encoding a 3-hydroxybutyryl-CoA dehydrogenase;
- c) a nucleic acid encoding a crotonase;
- d) a nucleic acid encoding a trans-enoyl-CoA reductase;
- e) a nucleic acid encoding a monofunctional aldehyde dehydrogenase;
- f) a nucleic acid encoding a monofunctional alcohol dehydrogenase;
- wherein one or more of the nucleic acids are recombinant,
- and wherein the host cell is capable of producing a C4 alcohol at concentrations that are at least 10-fold higher than the concentration of ethanol produced by the host cell.
A recombinant polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:
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A recombinant nucleic acid comprising a nucleotide sequence selected from the group consisting of SEQ ID NO:
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Dependencies are inferred from the claim text.