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US 12,674,185 B2Granted
Methods of producing morphinan alkaloids and derivatives
AssigneeAntheia, Inc.
InventorsChristina D. Smolke, Isis Trenchard, Kristy M. Hawkins, Catherine Thodey
Life of this patent
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Abstract
A method of producing promorphinan, morphinan, nal-opioid, and nor-opioid alkaloid products through the increased conversion of a promorphinan alkaloid to a morphinan alkaloid. The method comprises contacting the promorphinan alkaloid with at least one enzyme. Contacting the promorphinan alkaloid with the at least one enzyme converts the promorphinan alkaloid to a morphinan alkaloid.
Claims20
An engineered non-plant cell, comprising:
- i) an epimerase,
- ii) a thebaine synthase;
- and
- iii) at least one modification selected from the group consisting of:
- a) a substrate inhibition alleviating mutation, b) a product inhibition alleviating mutation, c) a cofactor recovery promoting mechanism, d) a feedback inhibition alleviating mutation, e) transcriptional modulation modification, and f) an inactivating mutation;
- and
- iv) wherein the cell further comprises three or more of the enzymes of:
- (a) tyrosinase or tyrosine hydroxylase (TYR or TyrH), L-DOPA decarboxylase (DODC), 6-O-methyltransferase (6OMT), coclaurine-N-methyltransferase (CNMT), N-methylcoclaurine 3′-hydroxylase (CYP80B1), 4′-O-methyltransferase (4′OMT), salutaridine synthase (SalSyn), salutaridine reductase (SalR), salutaridinol 7-O-acetyltransferase (SalAT), and norcoclaurine synthase (NCS);
- or
- (b) TYR or TyrH, DODC, monoamine oxidase (maoA), 6OMT, CNMT, 4′OMT, DRS-DRR, SalSyn, SalR, SalAT, and norcoclaurine synthase (NCS), and
- wherein, within the engineered non-plant cell, the engineered non-plant cell converts a precursor of a promorphinan molecule to an alkaloid product selected from the group consisting of:
- i) a morphinan alkaloid, ii) a nal-opioid alkaloid, and iii) a nor-opioid alkaloid.
9 more elements
A method of converting a precursor of a promorphinan molecule to a thebaine, or a derivative thereof, comprising:
- contacting the precursor of a promorphinan molecule with an epimerase and a thebaine synthase, wherein at least one precursor of promorphinan molecule is produced within an engineered non-plant cell where the conversion occurs,
- wherein the cell further comprises three or more of the enzymes of:
- (a) tyrosinase or tyrosine hydroxylase (TYR or TyrH), L-DOPA decarboxylase (DODC), 6-O-methyltransferase (6OMT), coclaurine-N-methyltransferase (CNMT), N-methylcoclaurine 3′-hydroxylase (CYP80B1), (4′-O-methyltransferase) (4′OMT), salutaridine synthase (SalSyn), salutaridine reductase (SalR), salutaridinol 7-O-acetyltransferase (SalAT), and norcoclaurine synthase (NCS);
- or
- (b) TYR or TyrH, DODC, monoamine oxidase (maoA), 6OMT, CNMT, 4′OMT, DRS-DRR, SalSyn, SalR, SalAT, and norcoclaurine synthase (NCS) and
- wherein contacting the precursor of a promorphinan molecule with the epimerase and thebaine synthase converts the precursor of a promorphinan molecule to a thebaine, or a derivative thereof, within the engineered non-plant cell.
3 more elements
Dependencies are inferred from the claim text.