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An Explanation of Cannabidiolic Acid (CBDA) Synthase –

Cannabidiolic acid (CBDA) synthase is the organic enzyme accountable for catalyzing the oxidocyclization of cannabigerolic acid (CBGA) into CBDA within the fiber-type Hashish sativa L. [1] CBDA dominates as a cannabinoid constituent within the plant.

The activating enzyme options solely a single polypeptide and is much like the NH2-terminal amino acid sequence of Delta1-tetrahydrocannabinolic-acid synthase.

To be able to set off the oxidocyclization response, CBDA synthase doesn’t have to have molecular oxygen, coenzymes, steel ion cofactors, or hydrogen peroxide. Which means CBDA synthase can’t be labeled as both a peroxidase or oxygenase — certainly, it’s enzymatic cyclization strikes ahead with out oxygenated intermediates.

CBDA is generally biosynthesized from cannabigerolic acid, extra so than cannabinerolic acid.

Reseachers have discovered, by CDNA encoding by polymerase-based chain reactions with gene-specific and degenerate primers, by reverse transcription and by a biochemical identification of the recombinant enzyme, that CBDA synthase is a covalently flavinylated oxidase. [2]

The practical and structural properties of the synthase are extremely akin to these of tetrahydrocannabinolic-acid (THCA) synthase, which biosynthesizes THCA, a cannabinoid in Hashish vegetation that give solution to medicine.

Together with THCA synthase, CBDA synthase, with three merchandise nonetheless not recognized, type 5 main cannibinoids of Hashish sativa L. That’s, geranylpyrophosphate, olivetolate geranyltransferase,  THCA, CBDA and cannabichromenic acid (CBCA). [3]

These cannabinoids are well-known and their pharmacological properties have been studied by many a workforce of researchers. The biosynthetic enzymes are purified from younger rapidly increasing plant leaves of C. sativa. [4]

The practical, structural, and genetic hyperlink between THCA synthase and CBDA synthase is of a lot curiosity to scientists. Related with the substrate CBGA, the 2 enzymes catalyze oxidocyclization reactions, as has already been talked about above.

In a single examine, scientists aligned the amino acid sequences of the 2 synthases and concluded that the construction of CBDA synthase has excessive degree of homology to that of THCA synthase. Certainly, an 84% id in a 544-amino acid overlap.

This id proves an evolutional relationship between the 2 enzymes, and signifies that the 2 synthases derived from a typical ancestor.

The 2 chemotype-determining cannabinoids, are biosynthesized with mechanisms of comparable response in each drug-type and fiber-type Hashish vegetation. The 2 enzymes appear broadly distributed within the plant kingdom. [5]



[1] Taura F, Morimoto S, Shoyama Y. Taura F, et al. Purification and characterization of cannabidiolic-acid synthase from Hashish sativa L.. Biochemical evaluation of a novel enzyme that catalyzes the oxidocyclization of cannabigerolic acid to cannabidiolic acid. J Biol Chem. 1996 Jul 19;271(29):17411-6. doi: 10.1074/jbc.271.29.17411.


[2] Taura F, Sirikantaramas S, Shoyama Y, Yoshikai Okay, Shoyama Y, Morimoto S. Taura F, et al. Cannabidiolic-acid synthase, the chemotype-determining enzyme within the fiber-type Hashish sativa. FEBS Lett. 2007 Jun 26;581(16):2929-34. doi: 10.1016/j.febslet.2007.05.043. Epub 2007 Might 25.


[3] Zirpel B, Kayser O, Stehle F. Zirpel B, et al. Elucidation of structure-function relationship of THCA and CBDA synthase from Hashish sativaL. J Biotechnol. 2018 Oct 20;284:17-26. doi: 10.1016/j.jbiotec.2018.07.031. Epub 2018 Jul 24.


[4] Sirikantaramas S, Taura F, Morimoto S, Shoyama Y. Sirikantaramas S, et al. Latest advances in Hashish sativa analysis: biosynthetic research and its potential in biotechnology. Curr Pharm Biotechnol. 2007 Aug;8(4):237-43. doi: 10.2174/138920107781387456.


[5] Aryal, N., Orellana, D.F. & Bouie, J. Distribution of cannabinoid synthase genes in non-Hashish organisms. J Hashish Res 1, 8 (2019)

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