Talk:CBDA synthase

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

Use this page for verification notes, disputes, and action items. Keep narrative content on the article.

Page scope

CBDA synthase covers the enzyme that makes cannabidiolic acid from cannabigerolic acid, and the gene that encodes it: the reaction and its products, the protein and its structure, the forms the gene takes, how its genotype relates to a plant's ratio of the two main cannabinoids, its position in the genome, the origin of the enzyme family 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 THCA 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

Taura, Morimoto and Shoyama (1996), Journal of Biological Chemistry: the purification of the enzyme from the rapidly expanding leaves of a cannabidiolic-acid-rich plant, its mass of 74 kilodaltons and isoelectric point of 6.1, the finding that it needed no coenzyme, oxygen or metal ion, and the slower conversion of cannabinerolic acid.
Taura and colleagues (2007), FEBS Letters: the cloning of the gene from a fibre-crop plant, the recombinant enzyme as a covalently flavinylated oxidase, the identity of 83.9 per cent with tetrahydrocannabinolic acid synthase, the common ancestor proposed for the two, and two further gene copies in the same plant that made no active enzyme.
Tahir and colleagues (2021), Journal of Cannabis Research: the 517-residue sequence and calculated mass of about 59 kilodaltons against the measured 74, the sugars added after the protein is made, and the difference in the proton-transfer step between the two enzymes.
Domenech and colleagues (2026), Current Research in Structural Biology: the structure at 1.70 ångström, the sequence identities among the three synthases, the conserved active-site residues, the changes that alter the active site of this enzyme and the missing serine behind the offset in residue numbering.
Zirpel, Kayser and Stehle (2018), Journal of Biotechnology: the products of both enzymes in yeast and the variants with raised activity, among them the change at position 414.
Van Velzen and Schranz (2021), Genome Biology and Evolution; Onofri, de Meijer and Mandolino (2015), Phytochemistry; Cascini and colleagues (2019), Plants: the clade classification, the working and defective sequence types and the plants they come from, and the four-base deletion in the shortened sequences of drug-crop plants.
Wenger and colleagues (2020), American Journal of Botany: feral plants of Minnesota genotyped and measured, the frequencies of the three chemotype groups, the test cross, the 20 clinical cultivars supplied blind and the Canadian grain cultivars.
Laverty and colleagues (2019), Genome Research; Grassa and colleagues (2021), New Phytologist; Lynch and colleagues (2025), Nature: the position of the gene, the retrotransposon-rich regions, the hemp ancestry of the gene in CBDRx, the expression in plants of each chemotype and the pangenome of 193 genomes.
Villard and colleagues (2025), Plant Biotechnology Journal: the reconstructed ancestral enzymes, their products and their activities beside those of the living enzymes.
Luo and colleagues (2019), Nature: the complete pathway in Saccharomyces cerevisiae and the propyl cannabinoids made from a shorter fatty acid.

Where the sources disagree

Whether the enzyme needs oxygen. The 1996 study of the enzyme purified from the plant found no requirement for a coenzyme, for molecular oxygen or for a metal ion. The 2007 study of the recombinant enzyme found a covalently bound flavin, a requirement for oxygen and the release of hydrogen peroxide.
The mass of the protein. The purified enzyme measured 74 kilodaltons. The coding sequence gives about 59 kilodaltons, and the difference is attributed to sugars added to the protein after it is made.
Sequence identity with tetrahydrocannabinolic acid synthase. Taura and colleagues give 83.9 per cent and the 2026 structures give 84 per cent. The review of Tahir and colleagues 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 this enzyme for the ancestral form because sequences resembling it vary more than those resembling tetrahydrocannabinolic acid synthase. Van Velzen and Schranz attribute that variety to further gene lineages, and the reconstructed ancestors made more tetrahydrocannabinolic acid than anything else.
Whether the shortened sequences are the same gene. Van Velzen and Schranz state that it is unsettled whether the shortened sequences of drug-crop plants are variants of this gene or a separate locus, given how far they have diverged and how closely they are linked to tetrahydrocannabinolic acid synthase.

How far the evidence goes

The selectivity and activity figures were measured on enzymes produced in yeast at a set pH and temperature, not in the plant.
The agreement between genotype and ratio was complete in the feral plants tested and in the clinical cultivars, and held in the grain cultivars only in plants with more than 0.5 per cent total cannabinoids.
The share of the variation in the ratio attributed to this locus, 92 per cent, is from the second generation of one cross between a drug-type cultivar and the hemp Carmen.
The variants that leave plants accumulating cannabigerolic acid were described from named hybrid cultivars and one Turkish cultivar, and the article names those places as the sources' own.
The named varieties carrying each sequence type are those the studies sampled.

Terms

CBDAS: the enzyme and its gene, both written CBDA 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.
Cannabinerolic acid: the cis isomer of cannabigerolic acid, a second substrate the enzyme accepts.
Chemotype I, II and III: the classes dominated by tetrahydrocannabinol, by both cannabinoids and by cannabidiol, which this gene's working and non-working forms track.