Elucidation of structure-function relationship of THCA and CBDA synthase from Cannabis sativa L.

Journal of Biotechnology

“Cannabinoids are secondary natural products from the plant Cannabis sativa L.

Therapeutic indications of cannabinoids currently comprise a significant area of medicinal research.

We have expressed the Δ9-tetrahydrocannabinolic acid synthase (THCAS) and cannabidiolic acid synthase (CBDAS) recombinantly in Komagataella phaffii and could detect eight different products with a cannabinoid scaffold after conversion of the precursor cannabigerolic acid (CBGA).

Besides five products remaining to be identified, both enzymes were forming three major cannabinoids of C. sativa – Δ9-tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA) and cannabichromenic acid (CBCA).

These studies lay the groundwork for further research as well as biotechnological cannabinoid production.”

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Recent advances in Cannabis sativa research: biosynthetic studies and its potential in biotechnology.

“Cannabinoids, consisting of alkylresorcinol and monoterpene groups, are the unique secondary metabolites that are found only in Cannabis sativa. Tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabichromene (CBC) are well known cannabinoids and their pharmacological properties have been extensively studied. Recently, biosynthetic pathways of these cannabinoids have been successfully established. Several biosynthetic enzymes including geranylpyrophosphate:olivetolate geranyltransferase, tetrahydrocannabinolic acid (THCA) synthase, cannabidiolic acid (CBDA) synthase and cannabichromenic acid (CBCA) synthase have been purified from young rapidly expanding leaves of C. sativa. In addition, molecular cloning, characterization and localization of THCA synthase have been recently reported. THCA and cannabigerolic acid (CBGA), its substrate, were shown to be apoptosis-inducing agents that might play a role in plant defense. Transgenic tobacco hairy roots expressing THCA synthase can produce THCA upon feeding of CBGA. These results open the way for biotechnological production of cannabinoids in the future.”

http://www.ncbi.nlm.nih.gov/pubmed/17691992

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