Increased biosynthesis of benzylisoquinoline alkaloids and benzylisoquinoline alkaloid precursors in a recombinant host cell
AssigneeRiver Stone Biotech, LLC
InventorsEsben Halkjaer Hansen, Markus Schwab, Philipp Berninger, Fanny Delgrange, Franziska Grassinger
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Abstract
Recombinant microorganisms, plants, and plant cells are disclosed that have been engineered to have reduced levels or activity of one or more alcohol dehydrogenases or aldehyde reductases thereby increasing the production of benzylisoquinoline alkaloids and/or benzylisoquinoline alkaloid precursors.
Claims20
A recombinant yeast cell capable of producing one or more benzylisoquinoline alkaloids or benzylisoquinoline alkaloid precursors, or both, comprising:
- (a) reduced or eliminated enzymatic activity of Genes de Respuesta a Estres 2 (GRE2) comprising the amino acid sequence of SEQ ID NO:
- 7, or an amino acid sequence having at least 90% identity to SEQ ID NO:
- 7;
- and, optionally,
- (b) reduced or eliminated enzymatic activity of one or more alcohol dehydrogenases or other aldehyde reductases, or a combination thereof,
- wherein the activity of each of the enzymes in (a) and (b) is reduced or eliminated, and whereby the recombinant yeast cell is thereby capable of increased production of one or more benzylisoquinoline alkaloids or benzylisoquinoline alkaloid precursors, or both, than are produced in cells without reduced or eliminated activity of the enzymes.
A method for producing of a benzylisoquinoline alkaloid or a benzylisoquinoline alkaloid precursor, or both, comprising:
- (a) providing a recombinant yeast cell capable of producing one or more benzylisoquinoline alkaloids or benzylisoquinoline alkaloid precursors, or both, that has reduced or eliminated enzymatic activity of Genes de Respuesta a Estres 2 (GRE2) comprising the amino acid sequence of SEQ ID NO:
- 7, or an amino acid sequence having at least 90% identity to SEQ ID NO:
- 7;
- and, optionally, (ii) one or more alcohol dehydrogenases or other aldehyde reductases, or a combination thereof,
- (b) cultivating the recombinant yeast cell for a time sufficient for the recombinant yeast cell to produce a benzylisoquinoline alkaloid and/or a benzylisoquinoline alkaloid precursor;
- and, optionally,
- (c) isolating the benzylisoquinoline alkaloid and/or a benzylisoquinoline alkaloid precursor from the recombinant yeast cell or from the cultivation supernatant, thereby producing a benzylisoquinoline alkaloid and/or a benzylisoquinoline alkaloid precursor.
Dependencies are inferred from the claim text.