Chemical engineering processes and apparatus for the synthesis of compounds
The present invention provides methods for producing cannabinoids and cannabinoid analogs as well as a system for producing these compounds. The inventive method is directed to contacting a compound according to Formula I or Formula II with a cannabinoid synthase. Also described is a system for producing cannabinoids and cannabinoid analogs by contacting a THCA synthase with a cannabinoid precursor and modifying at least one property of the reaction mixture to influence the quantity formed of a first cannabinoid relative to the quantity formed of a second cannabinoid.
1. A system for producing cannabinoid products, comprising:
a fermentor holding a cell culture medium comprising genetically engineered yeast or bacterial cells producing and secreting a cannabinoid synthase which is tetrahydrocannabinolic acid (THCA) or cannabidiolic acid (CBDA) synthase into the medium;
a bioreactor containing a reaction mixture configured to interact the cannabinoid synthases with a compound of formula I to form one or more cannabinoid products which are synthesized by said synthases
wherein said formula I has the following chemical structure:
wherein
R is —OH:
R 1 is —H or —COOH;
R 2 is a C 1 -C 10 linear or branched alkyl wherein said C 1 -C 10 linear alkyl is selected from the group consisting of CH 3 , C 2 H 5 , C 3 H 7 , C 4 H 9 , C 6 H 13 , C 7 H 15 , C 8 H 17 , iso-propyl, sec-butyl, iso-butyl, neopentyl, 2-methyl hexyl, and 2,3-dimethyl hexyl;
R 3 is H; and
a control mechanism configured to regulate a property of the medium containing the cannabinoid synthase or to control a property of the reaction mixture to modify the amount of the one or more cannabinoid products; wherein the property of the reaction mixture is one or more of the ionic strength of the reaction, the pH of the reaction, the temperature of the reaction, or the pressure of the reaction, wherein the pH of said reaction mixture is from 4 to less than 8.
2. The system of claim 1 , further comprising a filter configured to separate the cells from the medium containing the cannabinoid synthase produced by the cells.
3. The system of claim 1 , wherein the control mechanism comprises a processing circuit and a display to control one or more properties of the reaction mixture.
4. The system of claim 1 , wherein the property of the medium containing the cannabinoid synthase is on or more of the oxygen level of the medium, the rate of agitation of the medium, the pH of the medium, or the flow rate of the medium into the bioreactor.
5. The system of claim 1 , wherein the bioreactor is a column bioreactor containing nickel, and wherein the cannabinoid synthase includes a tag configured to bond to nickel.
6. The system of claim 1 , wherein the bacterial cells are Escherichia coli cells.
7. The system of claim 1 , wherein the reaction mixture comprises a reagent and a solvent.
8. The system of claim 7 , wherein the solvent is one or more of dimethyl sulfoxide (DMSO), dimethyl formamide (DMF), iso-propoyl alcohol and cyclodextrin.
9. The system of claim 8 , wherein the concentration of the solvent in the reaction mixture is between 5% and 30% (w/v).
10. The system of claim 1 , wherein the cells are genetically modified to produce and secrete tetrahydrocannabinolic acid synthase (THCA synthase).
11. The system of claim 1 , wherein the cells are genetically modified to produce and secrete cannabidiolic acid synthase (CBDA synthase).
12. The system of claim 1 , to in the compound of formula I, R 2 is selected from the group consisting of CH 3 , C 2 H 5 , C 3 H 7 , C 4 H 9 , C 6 H 13 , C 7 H 15 , C 8 H 17 .
13. The system of claim 1 , wherein in the compound of formula I, R 2 is C 3 H 7 .