Benzylisoquinoline alkaloids (BIA) producing microbes, and methods of making and using the same

Patent metadata

Field	Value
Publication number	US-10988787-B2
Application number	US-201816191247-A
Country	US
Kind code	B2
Filing date	Nov 14, 2018
Priority date	Mar 15, 2013
Publication date	Apr 27, 2021
Grant date	Apr 27, 2021

Abstract

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.

First claim

What is claimed is:

1. A benzylisoquinoline alkaloid active pharmaceutical ingredient comprising a benzylisoquinoline alkaloid product selected from the group consisting of:
a) hydromorphone, wherein the benzylisoquinoline alkaloid active pharmaceutical ingredient also contains neomorphine; and
b) morphine, wherein the benzylisoquinoline alkaloid active pharmaceutical ingredient also contains neomorphine.

2. The benzylisoquinoline alkaloid active pharmaceutical ingredient of claim 1 , wherein the benzylisoquinoline alkaloid product comprises hydromorphone, and wherein the benzylisoquinoline alkaloid active pharmaceutical ingredient also contains neomorphine.

3. The benzylisoquinoline alkaloid active pharmaceutical ingredient of claim 1 , wherein the benzylisoquinoline alkaloid product comprises morphine, and wherein the benzylisoquinoline alkaloid active pharmaceutical ingredient also contains neomorphine.

4. A pharmaceutical product comprising:
at least one benzylisoquinoline alkaloid active pharmaceutical ingredient according to claim 1 .

5. The pharmaceutical product according to claim 4 , wherein the benzylisoquinoline alkaloid active pharmaceutical ingredient comprises hydromorphone and neomorphine.

6. The pharmaceutical product according to claim 4 , wherein the benzylisoquinoline alkaloid active pharmaceutical ingredient comprises morphine and neomorphine.

7. A benzylisoquinoline alkaloid active pharmaceutical ingredient comprising a benzylisoquinoline alkaloid product selected from the group consisting of:
a) hydromorphone, wherein the benzylisoquinoline alkaloid active pharmaceutical ingredient also contains a detectable amount of neomorphine; and
b) morphine, wherein the benzylisoquinoline alkaloid active pharmaceutical ingredient also contains a detectable amount of neomorphine.

8. The benzylisoquinoline alkaloid active pharmaceutical ingredient of claim 7 , wherein the benzylisoquinoline alkaloid product comprises hydromorphone, and wherein the benzylisoquinoline alkaloid active pharmaceutical ingredient also contains neomorphine.

9. The benzylisoquinoline alkaloid active pharmaceutical ingredient of claim 7 , wherein the benzylisoquinoline alkaloid product comprises morphine, and wherein the benzylisoquinoline alkaloid active pharmaceutical ingredient also contains neomorphine.

10. A pharmaceutical product comprising:
at least one benzylisoquinoline alkaloid active pharmaceutical ingredient according to claim 7 .

11. The pharmaceutical product according to claim 10 , wherein the benzylisoquinoline alkaloid active pharmaceutical ingredient comprises hydromorphone and neomorphine.

12. The pharmaceutical product according to claim 10 , wherein the benzylisoquinoline alkaloid active pharmaceutical ingredient comprises morphine and neomorphine.

Assignees

• Univ Leland Stanford Junior

Inventors

• Smolke Christina D
• Thodey Catherine
• Trenchard Isis
• Galanie Stephanie

Classifications

• C12Y201/01116

  3'-Hydroxy-N-methyl-(S)-coclaurine 4'-O-methyltransferase (2.1.1.116) · CPC title

• C12N15/52

  Genes encoding for enzymes or proenzymes · CPC title

• C12P17/182 Primary

  Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system (alloxazine or isoalloxazine, e.g. riboflavine C12P25/00) · CPC title

• C12Y121/03003

  Reticuline oxidase (1.21.3.3) · CPC title

• C12P17/18

  containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin {(e.g. Rifamycin C12P17/189)} · CPC title