Biosynthesis of benzylisoquinoline alkaloids and benzylisoquinoline alkaloid precursors
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 host cell capable of producing one or more benzylisoquinoline alkaloids or benzylisoquinoline alkaloid precursors, or both, comprising:
- (a) reduced or eliminated enzymatic activity of Aldehyde Reductase Intermediate 1 (ARI1) (SEQ ID NOs:
- 15 & 16) or a homolog thereof;
- 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 by one or more genes encoding said enzyme being disrupted or deleted, and whereby the host 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 a gene encoding said enzymes.
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A method for producing of a benzylisoquinoline alkaloid or a benzylisoquinoline alkaloid precursor, comprising:
- (a) providing a recombinant host capable of producing one or more benzylisoquinoline alkaloids or benzylisoquinoline alkaloid precursors, or both, that has reduced or eliminated activity of (i) Aldehyde Reductase Intermediate 1 (ARI1) (SEQ ID NOs:
- 15 & 16) or a homolog thereof and, optionally, (ii) one or more alcohol dehydrogenases or other aldehyde reductases, or a combination thereof, wherein the activity of each of the enzymes in (i) and (ii) is reduced or eliminated by one or more genes encoding said enzyme being disrupted or deleted,
- (b) cultivating said recombinant host for a time sufficient for said recombinant host 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 said recombinant host or from the cultivation supernatant, thereby producing a benzylisoquinoline alkaloid and/or a benzylisoquinoline alkaloid precursor.
15-16. (canceled)
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Dependencies are inferred from the claim text.