Talk:THCA synthase

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Discussion for: THCA synthase • View • Links • Related changes

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Page scope

THCA synthase covers the enzyme that makes tetrahydrocannabinolic acid from cannabigerolic acid, and the gene that encodes it: the reaction and its products, the protein and its structure, where in the plant the enzyme works, the forms the gene takes across plants and landraces, its position in the genome, the origin of the enzyme family, what cannabinoids do for the plant and the production of the enzyme outside cannabis. The classification of plants by their cannabinoid proportions is treated at Chemotype, the other two enzymes at CBDA synthase and CBCA synthase, and marker assays at Genetic marker.

Data verification

Record source conflicts, figures that differ between studies and the limits of what each study tested. Keep narrative content on the article.

Discussion

Sources

Sirikantaramas and colleagues (2004), Journal of Biological Chemistry: the cloning of the gene from rapidly expanding leaves of a Mexican plant, the 545-residue polypeptide with a 28-residue signal peptide, flavin dependence and the histidine 114 mutant, the homology to the berberine bridge enzyme, and tobacco hairy roots that made the acid when fed cannabigerolic acid.
Sirikantaramas and colleagues (2005), Plant and Cell Physiology: expression confined to the secretory cells of the glandular trichomes, activity in the storage cavity content, and the fluorescent fusion protein in the trichome head.
Shoyama and colleagues (2012), Journal of Molecular Biology: the structure at 2.75 ångström, the two domains, the flavin bound to histidine 114 and cysteine 176, the hydride transfer, tyrosine 484 in place of the berberine bridge enzyme's glutamate 442, and the histidine 292 and tyrosine 417 mutants.
Domenech and colleagues (2026), Current Research in Structural Biology: structures of all three cannabinoid synthases with their flavin, the resolutions, the sequence identities between them, the conserved active-site residues and the differences in the active site of cannabidiolic acid synthase.
Kojoma and colleagues (2006), Forensic Science International: 13 strains, six of the drug crop and seven of the fibre crop, two gene variants with 37 substitutions between the deduced proteins, and a marker that amplified only in the drug-crop plants.
Onofri, de Meijer and Mandolino (2015), Phytochemistry; van Velzen and Schranz (2021), Genome Biology and Evolution; Cascini and colleagues (2019), Plants: sequence variants across chemotypes, the clade classification of the gene family, and the substitutions that separate the fibre crop from the drug crop.
Garfinkel, Otten and Crawford (2021), Genes: the change at base 1,064 that puts asparagine at position 355, its homozygous state in plants dominated by cannabigerolic acid, and its inheritance in two crossing populations.
Laverty and colleagues (2019), Genome Research; Grassa and colleagues (2021), New Phytologist; Lynch and colleagues (2025), Nature: the position of the gene in the genome, the retrotransposon-rich regions, the tandem arrays and the pangenome of 193 genomes.
Villard and colleagues (2025), Plant Biotechnology Journal: three reconstructed ancestral enzymes made in yeast, their products, and the residues behind the narrowing of their activity.
Stack and colleagues (2023), Horticulture Research: field and laboratory feeding trials with chewing insects. Li and colleagues (2025), Plant, Cell & Environment: 17 accessions under ultraviolet-B light.
Zirpel and colleagues (2018, two papers), Journal of Biotechnology; Luo and colleagues (2019), Nature: production of the enzyme in yeast, the engineered variants, and the complete pathway in Saccharomyces cerevisiae.
Morimoto and colleagues (2007), Journal of Biological Chemistry: the cannabinoid acids as agents of cell death in cannabis leaf tissue and cultured cells.

Where the sources disagree

Which chromosome the loci sit on. The genetic and physical map of 2019 places the two synthase loci on its chromosome 6. The assembly of CBDRx and the pangenome place the synthase arrays on chromosome 7. The numbering differs between assemblies; the arrangement described is the same.
The length of the reading frame. Sirikantaramas and colleagues give a reading frame of 1,635 nucleotides encoding 545 amino acids. Van Velzen and Schranz give 1,638 base pairs for the same gene.
How many copies a plant has. Amplicon studies reported several copies per plant. Van Velzen and Schranz attribute those counts to primers that also amplified the neighbouring cannabichromenic acid synthase, and the pangenome found at most one full-length copy per haploid genome.
Sequence identity with cannabidiolic acid synthase. Taura and colleagues give 83.9 per cent and the 2026 structures give 84 per cent. The review of Tahir and colleagues (2021) states 96 per cent in a sentence about cannabichromenic acid synthase, which agrees with neither.
Which enzyme the family started from. Onofri and colleagues took cannabidiolic acid synthase for the ancestral form because sequences resembling it vary more. Van Velzen and Schranz attribute that variety to further gene lineages, and Villard and colleagues, working with reconstructed ancestors, found the oldest active one unselective and making more tetrahydrocannabinolic acid than anything else.

How far the evidence goes

The activity and selectivity figures were measured on enzymes produced in yeast under set conditions of pH and temperature, not in the plant.
The substitutions said to lower the enzyme's activity in fibre-crop plants are predicted from the sequence. The studies that report them measured cannabinoids in the plants, not the activity of the altered enzymes.
The marker for dominance of cannabigerolic acid was tested in two crossing populations bred from one source plant, alongside cultivars of the same breeder.
The cell-death experiments were done on leaf tissue, isolated mitochondria and cultured cells of cannabis.
The ultraviolet-B finding rests on 17 accessions, on signals of selection in their sequences and on the enzyme expressed in other plant species. Its authors state the protective role as a proposal.
The sequence types named for Afghanistan, Korea, Pakistan and Tibet are single sequences or small sets from those places, held in sequence databases, and they describe the plants that were sampled.

Terms

THCAS: the enzyme and its gene, both written THCA synthase on the article.
Oxidocyclase: an enzyme that closes a ring by an oxidation. The three cannabinoid synthases are oxidocyclases of the berberine bridge enzyme-like family.
Chemotype IV: plants in which cannabigerolic acid predominates, the class to which the inactive variants of the gene lead.
B_T, B_D and B₀: the allele names of the single-locus model of chemotype inheritance, which the genome maps later resolved into separate genes.