Neurotransmitters and Methods of Making the Same

Abstract

In an aspect, the disclosure provides methods for making neurotransmitters in a host organism. The neurotransmitters can be cannabinoids and derivatives of cannabinoids. The host cells can be microalgae, fungi or other host cells. In a related aspect, the disclosure provides host cells engineered to have biochemical pathways for making neurotransmitters such as cannabinoids.

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         21 . A polynucleotide composition comprising a first nucleic acid encoding a hexanoyl-CoA synthase, a second nucleic acid encoding a 3,5,7-trioxododecanoyl-CoA synthase, a third nucleic acid encoding an olivetolic acid cyclase (or 3,5,7-trioxododecanoyl-CoA CoA-lyase), and a fourth nucleic acid encoding a geranyl-diphosphate:olivetolate geranyltransferase, wherein the first nucleic acid is operably linked to a control region, wherein the second nucleic acid is operably linked to a control region, wherein the third nucleic acid is operably linked to a control region, wherein the fourth nucleic acid is operably linked to a control region, and wherein the first nucleic acid, the second nucleic acid, the third nucleic acid, and the fourth nucleic acid are codon optimized for a  Prototheca.    
     
     
         22 . The polynucleotide composition of  claim 21 , wherein the first, second, third and fourth nucleic acids are in the same polynucleotide. 
     
     
         23 . The polynucleotide of  claim 21 , wherein at least one of the first, second, third and fourth nucleic acids are in a different polynucleotide. 
     
     
         24 . The polynucleotide of  claim 21 , further comprising a fifth nucleic acid encoding a cannabichromenic acid synthase, wherein the fifth nucleic acid sequence is codon optimized for a  Prototheca.    
     
     
         25 . The polynucleotide of  claim 24 , wherein the first, the second, the third, the fourth, and the fifth nucleic acids are in the same polynucleotide. 
     
     
         26 . The polynucleotide of  claim 24 , wherein at least one of the first, the second, the third, the fourth, and the fifth nucleic acids are in a different polynucleotide. 
     
     
         27 . The polynucleotide of  claim 21 , further comprising a fifth nucleic acid encoding a cannabidiolic-acid synthase, wherein the fifth nucleic acid sequence is codon optimized for a  Prototheca.    
     
     
         28 . The polynucleotide of  claim 27 , wherein the first, the second, the third, the fourth, and the fifth nucleic acids are in the same polynucleotide. 
     
     
         29 . The polynucleotide of  claim 27 , wherein at least one of the first, the second, the third, the fourth, and the fifth nucleic acids are in a different polynucleotide. 
     
     
         30 . The polynucleotide of  claim 21 , further comprising a fifth nucleic acid encoding a Δ1-tetrahydrocannabinolic acid synthase, wherein the fifth nucleic acid sequence is codon optimized for a  Prototheca.    
     
     
         31 . The polynucleotide of  claim 30 , wherein the first, the second, the third, the fourth, and the fifth nucleic acids are in the same polynucleotide. 
     
     
         32 . The polynucleotide of  claim 30 , wherein at least one of the first, the second, the third, the fourth, and the fifth nucleic acids are in a different polynucleotide. 
     
     
         33 . The polynucleotide of  claim 24 , further comprising a sixth nucleic acid encoding a cannabidiolic-acid synthase, wherein the sixth nucleic acid sequence is codon optimized for a  Prototheca.    
     
     
         34 . The polynucleotide of  claim 33 , wherein the first, the second, the third, the fourth, the fifth, and the sixth nucleic acids are in the same polynucleotide. 
     
     
         35 . The polynucleotide of  claim 33 , wherein at least one of the first, the second, the third, the fourth, the fifth, and the sixth nucleic acids are in a different polynucleotide. 
     
     
         36 . The polynucleotide of  claim 33 , further comprising a seventh nucleic acid encoding a Δ1-tetrahydrocannabinolic acid synthase wherein the seventh nucleic acid sequence is codon optimized for a  Prototheca.    
     
     
         37 . The polynucleotide of  claim 36 , wherein the first, the second, the third, the fourth, the fifth, the sixth, and the seventh nucleic acids are in the same polynucleotide. 
     
     
         38 . The polynucleotide of  claim 36 , wherein at least one of the first, the second, the third, the fourth, the fifth, the sixth, and the seventh nucleic acids are in a different polynucleotide. 
     
     
         39 . The polynucleotide of  claim 30 , further comprising a sixth nucleic acid encoding a cannabidiolic-acid synthase, wherein the sixth nucleic acid sequence is codon optimized for a  Prototheca.    
     
     
         40 . The polynucleotide of  claim 39 , wherein the first, the second, the third, the fourth, the fifth, and the sixth nucleic acids are in the same polynucleotide.