Recombinant microorganisms and methods for producing cannabinoids and cannabinoid derivatives
AssigneeThe Regents of the University of California
InventorsJay D. Keasling, Leo D'Espaux, Jeff Wong, Xiaozhou Luo, Michael Reiter, Charles Denby, Anna Lechner
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Abstract
The present disclosure provides genetically modified host cells that produce a cannabinoid, a cannabinoid derivative, a cannabinoid precursor, or a cannabinoid precursor derivative. The present disclosure provides methods of synthesizing a cannabinoid, a cannabinoid derivative, a cannabinoid precursor, or a cannabinoid precursor derivative.
Claims15
A genetically modified yeast cell for producing a cannabinoid or a cannabinoid derivative, the genetically modified yeast cell comprising one or more heterologous nucleic acids integrated into a chromosome of the genetically modified yeast cell and encoding a geranyl pyrophosphate:olivetolic acid geranyltransferase polypeptide comprising the amino acid sequence of SEQ ID NO:110 or SEQ ID NO:100.
A method of producing a cannabinoid or a cannabinoid derivative, the method comprising:
- a) culturing a genetically modified yeast cell comprising:
- i) one or more heterologous nucleic acids integrated into a chromosome of the genetically modified yeast cell and encoding a geranyl pyrophosphate:olivetolic acid geranyltransferase polypeptide comprising the amino acid sequence of SEQ ID NO:110 or SEQ ID NO:100;
- and
- ii) one or more heterologous nucleic acids integrated into a chromosome of the genetically modified yeast cell and encoding a tetraketide synthase (TKS) polypeptide comprising the amino acid sequence of SEQ ID NO:11;
- and/or
- iii) one or more heterologous nucleic acids integrated into a chromosome of the genetically modified yeast cell and encoding an olivetolic acid cyclase (OAC) polypeptide comprising the amino acid sequence of SEQ ID NO:10;
- in a suitable medium containing a carboxylic acid;
- and
- b) recovering the produced cannabinoid or cannabinoid derivative.
A method of producing a cannabinoid or cannabinoid derivative, the method comprising:
- a) culturing a genetically modified yeast cell comprising:
- i) one or more heterologous nucleic acids integrated into a chromosome of the genetically modified yeast cell and encoding a geranyl pyrophosphate:olivetolic acid geranyltransferase polypeptide comprising the amino acid sequence of SEQ ID NO:110 or SEQ ID NO:100;
- ii) one or more heterologous nucleic acids integrated into a chromosome of the genetically modified yeast cell and encoding a tetraketide synthase (TKS) polypeptide comprising the amino acid sequence of SEQ ID NO:11;
- iii) one or more heterologous nucleic acids integrated into a chromosome of the genetically modified yeast cell and encoding an olivetolic acid cyclase (OAC) polypeptide comprising the amino acid sequence of SEQ ID NO:10;
- iv) one or more heterologous nucleic acids encoding a THCA synthase polypeptide comprising the amino acid sequence of SEQ ID NO:155 or a CBDA synthase polypeptide comprising the amino acid sequence of SEQ ID NO:88 or SEQ ID NO:151;
- v) one or more heterologous nucleic acids encoding one or more polypeptides that generate geranyl pyrophosphate, wherein the polypeptide that generates geranyl pyrophosphate is a geranyl pyrophosphate synthetase (GPPS) polypeptide comprising the amino acid sequence of SEQ ID NO:60;
- vi) one or more heterologous nucleic acids encoding one or more polypeptides that generate an acyl-CoA compound or an acyl-CoA compound derivative wherein the polypeptide that generates an acyl-CoA compound or an acyl-CoA compound derivative is an acyl-activating enzyme (AAE) polypeptide comprising the amino acid sequence of SEQ ID NO:90, SEQ ID NO:92, or SEQ ID NO:149;
- a fatty acyl-CoA ligase polypeptide comprising the amino acid sequence of SEQ ID NO:145 or SEQ ID NO:147;
- or a fatty acyl-CoA synthetase (FAA) polypeptide comprising the amino acid sequence of SEQ ID NO:169, SEQ ID NO:192, SEQ ID NO:194, SEQ ID NO:196, SEQ ID NO:198, or SEQ ID NO:200;
- and
- vii) one or more heterologous nucleic acids encoding one or more polypeptides that generate malonyl-CoA, wherein the polypeptide that generates malonyl-CoA is an acetyl-CoA carboxylase-1 (ACC1) polypeptide comprising the amino acid sequence of SEQ ID NO:9, SEQ ID NO:97, or SEQ ID NO:207;
- in a suitable medium;
- and
- b) recovering the produced cannabinoid or cannabinoid derivative.
A method of producing a cannabinoid or a cannabinoid derivative, the method comprising use of a genetically modified yeast cell comprising a heterologous nucleic acid integrated into a chromosome of the genetically modified yeast cell and encoding a geranyl pyrophosphate:olivetolic acid geranyltransferase polypeptide comprising the amino acid sequence of SEQ ID NO:110 or SEQ ID NO:100.
Dependencies are inferred from the claim text.