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AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsChristina D. Smolke, Catherine Thodey, Isis Trenchard, Stephanie Galanie
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Aspects of the invention include host cells that are engineered to produce benzylisoquinoline alkaloids (BIAs). The host cells include heterologous coding sequences for a variety of enzymes involved in synthetic pathways from starting compounds to BIAs of the host cell. Also provided are methods of producing the BIAs of interest by culturing the host cells under culture conditions that promote expression of enzymes encoded by the heterologous coding sequences of the host cells. Aspects of the invention further include compositions, e.g., host cells, starting compounds and kits, etc., that find use in methods of the invention.
-168. (canceled)
An engineered non-plant cell that produces a benzylisoquinoline alkaloid product, said engineered non-plant cell comprising a plurality of heterologous coding sequences for encoding a plurality of enzymes within a pathway for producing the benzylisoquinoline alkaloid product, wherein at least one heterologous coding sequence of the plurality of heterologous coding sequences encodes an enzyme that is within a pathway that converts a thebaine to the benzylisoquinoline alkaloid product, and wherein the benzylisoquinoline alkaloid product is selected from the group consisting of a neopinone, neopine, neomorphine, codeinone, codeine, morphine, oripavine, morphinone, hydrocodone, 14-hydroxycodeinone, dihydrocodeine, oxycodone, 14-hydroxycodeine, hydromorphone, and dihydromorphine.
An engineered non-plant cell that produces a benzylisoquinoline alkaloid product, said engineered non-plant cell comprising a plurality of heterologous coding sequences for encoding a plurality of enzymes within a pathway for producing the benzylisoquinoline alkaloid product, wherein at least one heterologous coding sequence of the plurality of heterologous coding sequences encodes an enzyme that is within a pathway that converts a thebaine to the benzylisoquinoline alkaloid product, wherein one enzyme of the plurality of enzymes is Salutaridine synthase, and wherein the benzylisoquinoline alkaloid product is selected from the group consisting of a salutaridine, salutaridinol, 7-O-acetylsalutaridinol, thebaine, neopinone, neopine, neomorphine, codeinone, codeine, morphine, oripavine, morphinone, hydrocodone, 14-hydroxycodeinone, dihydrocodeine, oxycodone, 14-hydroxycodeine, hydromorphone, and dihydromorphine.
A product stream generated from cultured engineered non-plant cells, the product stream comprising detectable amounts of at least two components selected from the group consisting of a thebaine, neopinone, codeinone, neopine, codeine, neomorphine, morphine, oripavine, morphinone, hydrocodone, 14-hydroxycodeinone, dihydrocodeine, oxycodone, 14-hydroxycodeine, hydromorphone, and dihydromorphine.
Dependencies are inferred from the claim text.