Apparatus and methods for biosynthetic production of cannabinoids

An apparatus for producing tetrahydrocannabinolic acid (THCA) and cannabichromenic acid (CBCA) in different ratios or cannabidiolic acid (CBDA) and cannabichromenic acid (CBCA) in different ratios, wherein the apparatus comprises:

• (i) a bioreactor comprising (a) an automated supply system configured to deliver a first automated supply of cannabigerolic acid (CBGA), a cannabinoid acid synthase, and a reaction mixture;
• and (b) a second automated system to cease the reaction;
• (ii) a controller configured to modify a property of the reaction mixture, wherein the property of the reaction mixture is one or more properties of a reaction solvent, an ionic strength of a reaction medium, a temperature of the reaction, a reaction pressure, a viscosity of the reaction mixture, a pH of the reaction mixture, a concentration of the reagents, or a concentration of an amphiphilic compound to produce tetrahydrocannabinolic acid (THCA) and cannabichromenic acid (CBCA) when the cannabinoid synthase is a tetrahydrocannabinolic acid synthase (THCA synthase) that comprises a nucleic acid sequence represented by SEQ ID NO:
• 1 or SEQ ID NO:
• 3 or a variant or a fragment thereof, or a nucleic acid sequence that encodes a polypeptide comprising SEQ ID NO:
• 2 or SEQ ID NO:
• 4, or a variant or a fragment thereof;
• or cannabidiolic acid (CBDA) and cannabichromenic acid (CBCA) when the cannabinoid synthase is a cannabinolic acid synthase (CBDA synthase) that comprises a nucleic acid sequence represented by SEQ ID NO:
• 5 or SEQ ID NO:
• 7 or a variant or a fragment thereof, or a nucleic acid sequence that encodes a polypeptide comprising SEQ ID NO:
• 6 or SEQ ID NO:
• 8 or a variant or a fragment thereof;
• and (iii) an extractor configured to recover the tetrahydrocannabinolic acid (THCA) and cannabichromenic acid (CBCA) or the cannabidiolic acid (CBDA) and cannabichromenic acid (CBCA) so produced.