Host cells capable of producing retinol or retinol precursors and methods of use thereof
AssigneeAmyris, Inc.
InventorsVictoria HSIAO, Simone M. MANTOVANI, William E. DRAPER, Anna TAI, Yue YANG
Life of this patent
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Abstract
Provided herein are recombinant host cells, compositions, and methods for the production of retinol, retinal, beta-carotene, lycopene, or phytoene (retinol or retinol precursor). The host cells are genetically modified to contain heterologous nucleic acids that express novel enzymes that enable the host cell to produce the retinol or retinol precursor from a carbon source such as sucrose. The host cells, compositions, and methods disclosed herein provide an efficient route for the heterologous production of retinol, retinal, beta-carotene, lycopene, or phytoene.
Claims31
A recombinant host cell capable of producing retinol comprising a heterologous nucleic acid that encodes a first polypeptide having a sequence having at least 90% identity to a sequence selected from SEQ ID NO:
- 10, SEQ ID NO:
- 153, SEQ ID NO:
- 154, SEQ ID NO:
- 155, SEQ ID NO:
- 156, and any one of SEQ ID NOs:
- 217-240;
- a heterologous nucleic acid that encodes a second polypeptide having a sequence having at least 90% identity to a sequence selected from SEQ ID NO:
- 11, SEQ ID NO:
- 150, SEQ ID NO:
- 151, SEQ ID NO:
- 152, and any one of SEQ ID NOs:
- 158-216;
- a heterologous nucleic acid that encodes a third polypeptide having a sequence having at least 90% identity to a sequence selected from SEQ ID NOs:
- 12 and 55-149;
- and a heterologous nucleic acid that encodes a fourth polypeptide having a sequence having at least 90% identity to a sequence selected from SEQ ID NOs:
- 14-54.
A recombinant host cell capable of producing lycopene comprising a heterologous nucleic acid that encodes a phytoene synthase, and comprising a heterologous nucleic acid that encodes a polypeptide having a sequence having at least 90% identity to a sequence selected from SEQ ID NO:
- 11, SEQ ID NO:
- 150, SEQ ID NO:
- 151, SEQ ID NO:
- 152, and any one of SEQ ID NOs:
- 158-216.
A recombinant host cell capable of producing beta-carotene comprising a heterologous nucleic acid that encodes a first polypeptide having a sequence having at least 90% identity to a sequence selected from SEQ ID NO:
- 10, SEQ ID NO:
- 153, SEQ ID NO:
- 154, SEQ ID NO:
- 155, SEQ ID NO:
- 156, and any one of SEQ ID NOs:
- 217-240, and comprising a heterologous nucleic acid that encodes a second polypeptide having a sequence having at least 90% identity to a sequence selected from SEQ ID NO:
- 11, SEQ ID NO:
- 150, SEQ ID NO:
- 151, SEQ ID NO:
- 152, and any one of SEQ ID NOs:
- 158-216.
A recombinant host cell capable of producing retinal comprising a heterologous nucleic acid that encodes a first polypeptide having a sequence having at least 90% identity to a sequence selected from SEQ ID NO:
- 10, SEQ ID NO:
- 153, SEQ ID NO:
- 154, SEQ ID NO:
- 155, SEQ ID NO:
- 156, and any one of SEQ ID NOs:
- 217-240;
- a heterologous nucleic acid that encodes a second polypeptide having a sequence having at least 90% identity to a sequence selected from SEQ ID NO:
- 11, SEQ ID NO:
- 150, SEQ ID NO:
- 151, SEQ ID NO:
- 152, and any one of SEQ ID NOs:
- 158-216;
- and a heterologous nucleic acid that encodes a third polypeptide having a sequence having at least 90% identity to a sequence selected from SEQ ID NOs:
- 12 and 55-149.
A recombinant host cell capable of producing phytoene comprising a heterologous nucleic acid that encodes a first polypeptide having at least 90% sequence identity to a sequence selected from SEQ ID NO:
- 10, SEQ ID NO:
- 153, SEQ ID NO:
- 154, SEQ ID NO:
- 155, SEQ ID NO:
- 156, and any one of SEQ ID NOs:
- 217-240.
The recombinant host cell of any of the preceding claims further comprising one or more heterologous nucleic acids that encode one or more polypeptides having a sequence having at least 90% identity to a sequence selected from SEQ ID NO:
- 3, SEQ ID NO:
- 1, SEQ ID NO:
- 7, SEQ ID NO:
- 157, SEQ ID NO:
- 2, SEQ ID NO:
- 8, SEQ ID NO:
- 5, SEQ ID NO:
- 6, and SEQ ID NO:
- 4.
The recombinant host cell of any one of the preceding claims, further comprising a heterologous nucleic acid encoding a geranylgeranyl diphosphate synthase having a sequence having at least 90% identity to a sequence selected from SEQ ID NOs:
- 9 and 289-310.
The recombinant host cell of any one of the preceding claims, wherein the recombinant host cell comprises a deletion of at least a portion of a native alcohol dehydrogenase gene.
The recombinant host cell of any one of the preceding claims, wherein the recombinant host cell further comprises an ERG9 gene that is downregulated relative to the parent strain.
The recombinant host cell of any one of the preceding claims, wherein the recombinant host cell further comprises a heterologous nucleic acid encoding a lycopene cyclase, wherein the lycopene cyclase has a sequence having at least 90% identity to a sequence selected from any one of SEQ ID NOs:
- 243-273.
The recombinant host cell of any one of the preceding claims, wherein the recombinant host cell further comprises a heterologous nucleic acid encoding a lycopene cyclase, wherein the lycopene cyclase has a sequence selected from any one of SEQ ID NOs:
- 243-273.
The recombinant host cell of any one of the preceding claims, wherein the host cell comprises a plant cell, a yeast cell, or a bacterial cell.
Dependencies are inferred from the claim text.