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. ##STR00001##
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.

The present disclosure features compositions and methods for producing one or more cannabinoids, such as cannabidiolic acid (CBDa) or cannabidiol (CBD), in a host cell, such as a yeast cell, that is genetically modified to express the enzymes of a cannabinoid biosynthetic pathway. Using the compositions and methods of the present invention, the host cell may be genetically modified to express one or more enzymes of a cannabinoid biosynthetic pathway, such as CBDaS. The host cell may be cultured in the medium in the presence of a first cannabinoid, for example CBGa, and incubated for a time sufficient to allow for bioconversion of the first cannabinoid to a second cannabinoid, for example CBDa, by the host cell.

The present disclosure relates generally to methods for the modification of plant cells, e.g., cannabis plant cells, using RNA interference (RNAi), and cells that have been modified to express mediators of RNAi, e.g., short interfering RNA (siRNA). The present disclosure further relates to plants comprising the modified cells and products derived from the plants, e.g., plant material and extracts derived therefrom and methods for selecting siRNA for altering the expression of one or more cannabinoid biosynthesis genes, such as THCAS, CBCAS or CBDAS.

The present invention provides an isolated DNA molecule including at least a first nucleic acid sequence encoding a first protein and at least a second nucleic acid sequence encoding a second protein, wherein the first protein and the second protein are derived from Helichrysum umbraculigerum and belonging to an enzyme family selected from: acyl activating enzyme (AAE), polyketide synthase (PKS), polyketide cyclase (PKC), prenyltransferase (PT), or cannabichromenic acid synthase (CBCAS), and wherein the first protein and the second protein belong to different enzyme families. Further provided are an artificial nucleic acid molecule including the isolated DNA molecule, a transgenic cell, a tissue, or a plant including same. Further provided is a method for synthesizing a cannabinoid, a precursor thereof, or any combination thereof.

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.

##STR00001##

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.

The present invention provides an apparatus and methods for producing tetrahydrocannabinolic acid (THCA), cannabichromenic acid (CBCA) and cannabichromenic acid (CBCA) in different ratios. 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 to produce the desired products; and (iii) an extractor configured to recover the tetrahydrocannabinolic acid (THCA), cannabichromenic acid (CBCA) or cannabidiolic acid (CBDA) and cannabichromenic acid.

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.

##STR00001##

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.

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.

##STR00001##

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.

The present invention provides an apparatus and methods for producing tetrahydrocannabinolic acid (THCA), cannabichromenic acid (CBCA) and cannabichromenic acid (CBCA) in different ratios. 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 to produce the desired products; and (iii) an extractor configured to recover the tetrahydrocannabinolic acid (THCA), cannabichromenic acid (CBCA) or cannabidiolic acid (CBDA) and cannabichromenic acid.

Aspects of the disclosure relate to biosynthesis of cannabinoids and cannabinoid precursors in recombinant cells and in vitro.