Methods and Compositions for Producing Cannabinoids
Disclosed herein are methods of producing one or more cannabinoid compounds, expanding cells that produce the compounds, cannabinoid compounds produced by the methods, pharmaceutical compositions comprising the cannabinoid compounds, and methods of producing and utilizing the compounds and compositions.
1 . A method of producing one or more cannabinoid compounds, comprising: incubating plant cells in a production medium, inside a bioreactor, under conditions where said plant cells produce said one or more cannabinoid compounds; thereby producing one or more cannabinoid compounds.
2 . The method of claim 1 , wherein said production medium comprises an elicitor.
3 . The method of claim 1 , wherein said plant cells are incubated in said production medium for at least 3 hours.
4 . The method of claim 1 , preceded by incubating said plant cells in a bioreactor, under conditions fostering expansion of the plant cells.
5 . The method of claim 4 , wherein said conditions comprise an expansion medium that differs from said production medium.
6 . The method of claim 5 , wherein said plant cells are incubated in said expansion medium for at least 3 population doublings.
7 . The method of claim 1 , wherein said plant cells are C. sativa cells.
8 . The method of claim 7 , wherein said C. sativa cells are trichome cells.
9 . The method of claim 8 , wherein said trichome cells are in clumps.
10 . The method of claim 8 , wherein said trichome cells are in a single-cell suspension.
11 . The method of claim 1 , wherein said plant cells comprise a gene that encodes a cannabinoid synthetic enzyme.
12 . The method of claim 11 , wherein the gene is operably linked to an inducible promoter.
13 . The method of claim 1 , wherein said plant cells comprise a gene that encodes a cannabinoid secretion enzyme.
14 . The method of claim 13 , wherein the gene is operably linked to an inducible promoter.
15 . The method of claim 1 , wherein said production medium comprises an inducing agent.
16 . The method of claim 1 , further comprising controlling at least one of pH, temperature, and levels of dissolved oxygen, glucose, lactate, lactate dehydrogenase, NH 3 , and glutamate.
17 . The method of claim 1 , wherein said bioreactor further comprises a synthetic three-dimensional growth substrate.
18 . The method of claim 1 , further comprising removing said one or more cannabinoid compounds from said production medium on an ongoing basis.
19 . A bioreactor, comprising: a plant cell, a production medium, and one or more cannabinoid compounds disposed in said production medium.
20 . The bioreactor of claim 19 , wherein said production medium comprises an elicitor.
21 . The bioreactor of claim 19 , wherein said plant cells are C. sativa cells.
22 . The bioreactor of claim 21 , wherein said C. sativa cells are trichome cells.
23 . The bioreactor of claim 22 , wherein said trichome cells are in clumps.
24 . The bioreactor of claim 22 , wherein said trichome cells are in a single-cell suspension.
25 . The bioreactor of claim 19 , wherein said plant cells comprise a gene that encodes a cannabinoid synthetic enzyme.
26 . The bioreactor of claim 19 , wherein said plant cells comprise a gene that encodes a cannabinoid secretion enzyme.
27 . The bioreactor of claim 19 , wherein said production medium comprises an inducing agent.
28 . The bioreactor of claim 19 , wherein said bioreactor is configured for further comprising controlling at least one of pH, temperature, and levels of dissolved oxygen, glucose, lactate, lactate dehydrogenase, NH 3 , and glutamate.
29 . The bioreactor of claim 19 , wherein said bioreactor further comprises a synthetic three-dimensional growth substrate.
30 . The bioreactor of claim 19 , wherein said bioreactor is configured for removing said one or more cannabinoid compounds from said production medium on an ongoing basis.