Genes and proteins for aromatic polyketide synthesis

1. A host cell transformed with: i) a nucleotide sequence as set forth in SEQ ID NO: 1 or 3 or a codon degenerate nucleotide sequence thereof; ii) a nucleotide sequence of 303 nucleotides that encodes a polypeptide with an amino acid sequence of SEQ ID NO: 2 or a conservatively substituted amino acid sequence thereof; or iii) a fragment of i) or ii) having a length of at least 300 base pairs; wherein the nucleic acid molecule encodes a polypeptide with polyketide cyclase activity.

2. A process of synthesizing an aromatic polyketide comprising: reacting an alkanoyl CoA with malonyl CoA in presence of a type III polyketide synthase enzyme and a polypeptide comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2 or a conservatively substituted amino acid sequence thereof, wherein the polypeptide has polyketide cyclase activity.

3. The process of claim 2 , wherein the alkanoyl CoA is CoA-S—C(O)—(CH 2 ) n —CH 3 , where n is an integer from 0 to 4.

4. The process of claim 3 , wherein the alkanoyl CoA comprises hexanoyl CoA.

5. The process of claim 2 , wherein the type III polyketide synthase enzyme is polyketide synthase/olivetol synthase.

6. The process of claim 2 wherein the aromatic polyketide is olivetolic acid.

7. A process of altering the level of a cannabinoid compound in a cannabis plant, cannabis cell or cannabis tissue comprising introducing a nucleic acid molecule into said cannabis plant, cannabis cell or cannabis tissue using a RNAi construct, amiRNA, VIGS virus, antisense oligonucleotide, a targeted mutagenesis construct or using Targeting Induced Local Lesions IN Genomes (TILLING) wherein the nucleic acid molecule or TILLING inhibits expression of SEQ ID NO: 1 or 3, or a part thereof, to silence a gene that encodes an enzyme with polyketide cyclase activity that catalyzes synthesis of an aromatic polyketide.

8. A process of altering the level of a cannabinoid compound in a cannabis plant, cannabis cell or cannabis tissue comprising introducing and expressing or over-expressing in the cannabis plant, cannabis cell or cannabis tissue a nucleic acid molecule selected from the group consisting of i) a nucleotide sequence as set forth in SEQ ID NO: 1 or 3 or a codon degenerate nucleotide sequence thereof; ii) a nucleotide sequence of 303 nucleotides that encodes a polypeptide with an amino acid sequence of SEQ ID NO: 2 or a conservatively substituted amino acid sequence thereof; and iii) a fragment of i) or ii) having a length of at least 300 base pairs; wherein the nucleic acid molecule encodes a polypeptide with polyketide cyclase activity, and selecting a cannabis plant, cannabis cell or cannabis tissue with altered levels of the cannabinoid compound, wherein the cannabis plant, cannabis cell or cannabis tissue contains the nucleic acid molecule.

9. A process of altering the level of a cannabinoid compound in a microorganism, plant, plant cell or plant tissue comprising expressing or over-expressing in the microorganism, plant, plant cell or plant tissue i) a nucleotide sequence as set forth in SEQ ID NO: 1 or 3 or a codon degenerate nucleotide sequence thereof; ii) a nucleotide sequence of 303 nucleotides that encodes a polypeptide with an amino acid sequence of SEQ ID NO: 2 or a conservatively substituted amino acid sequence thereof; or iii) a fragment of i) or ii) having a length of at least 300 base pairs; wherein the nucleic acid molecule encodes a polypeptide with polyketide cyclase activity, and wherein the microorganism, plant, plant cell or plant tissue expresses a polynucleotide encoding one or more other enzymes in a cannabinoid biosynthetic pathway.

10. A process of altering the level of a cannabinoid compound in a microorganism, plant, plant cell or plant tissue comprising expressing or over-expressing in the microorganism, plant, plant cell or plant tissue a nucleic acid molecule encoding a polypeptide comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2 or a conservatively substituted amino acid sequence thereof, wherein the polypeptide has polyketide cyclase activity and wherein the microorganism, plant, plant cell or plant tissue expresses a polynucleotide encoding one or more other enzymes in a cannabinoid biosynthetic pathway.

11. A process of synthesizing a naturally-occurring cannabinoid compound or a non-naturally occurring analog of a cannabinoid compound comprising expressing in the microorganism, plant, plant cell or plant tissue i) a nucleotide sequence as set forth in SEQ ID NO: 1 or 3 or a codon degenerate nucleotide sequence thereof; ii) a nucleotide sequence of 303 nucleotides that encodes a polypeptide with an amino acid sequence of SEQ ID NO: 2 or a conservatively substituted amino acid sequence thereof; iii) a fragment of i) or ii) having a length of at least 300 base pairs; or iv) a nucleotide sequence encoding a polypeptide comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2 or a conservatively substituted amino acid sequence thereof, in the presence of a type III polyketide synthase enzyme, an alkanoyl CoA and malonyl CoA, and wherein the nucleotide sequence encodes a polypeptide with polyketide cyclase activity.

12. A process of synthesizing an aromatic polyketide in an in vitro cell-free reaction, said process comprising: reacting an acyl carboxylic acid with coenzyme A through the action of an acyl CoA synthetase to form an alkanoyl CoA in presence of a type III polyketide synthase enzyme and a polypeptide comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2 or a conservatively substituted amino acid sequence thereof, wherein the polypeptide has polyketide cyclase activity.

13. The host cell of claim 1 , wherein the cell is a yeast cell or a bacteria.