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Updated: Aug 6, 2026
08:18
Non-Aqueous Isolation and Enrichment of Glandular Capitate Stalked and Sessile Trichomes from Cannabis sativa
Published on: May 12, 2023
X-ray crystal structures of the cannabinoid synthases CBCAS, CBDAS and THCAS
Jack Domenech1, Andrew King2, Edward Byrne2
1Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK.
Current Research in Structural Biology
|July 26, 2026
Summary
Researchers report high-resolution structures of Cannabichromenic Acid Synthase (CBCAS), Cannabidiolic Acid Synthase (CBDAS), and Tetrahydrocannabinolic Acid Synthase (THCAS). These structures reveal key active site differences, aiding the engineering of cannabinoid biosynthesis.
Area of Science:
- Biochemistry
- Structural Biology
- Synthetic Biology
Background:
- Cannabinoid synthase enzymes (CBCAS, CBDAS, THCAS) synthesize valuable pharmaceutical compounds from Cannabigerolic Acid (CBGA).
- Understanding these enzymes is crucial for heterologous production and synthetic biology applications.
- Previous structural data was limited, with only THCAS structure previously reported.
Purpose of the Study:
- To present high-resolution crystal structures of CBCAS, CBDAS, and THCAS in complex with their FAD coenzyme.
- To elucidate the structural basis for the distinct substrate specificities of these homologous enzymes.
- To provide a foundation for rational engineering of cannabinoid synthases.
Main Methods:
- X-ray crystallography was used to determine the structures of CBCAS, CBDAS, and THCAS.
- Structures were solved at high resolution, revealing detailed active site features.
- Enzyme-FAD complexes were analyzed to understand coenzyme interactions.
Main Results:
- High-resolution structures for CBCAS, CBDAS, and an improved resolution structure for THCAS were obtained.
- Detailed active site differences were identified, including subtle amino acid substitutions and topological variations.
- These structural variations correlate with the enzymes' distinct catalytic activities and substrate specificities.
Conclusions:
- The presented structures offer unprecedented insight into the molecular mechanisms of cannabinoid biosynthesis.
- Structural information can guide the rational engineering of CBCAS, CBDAS, and THCAS for improved or altered chemoselectivity.
- This work facilitates the development of efficient industrial production of cannabinoids via synthetic biology.
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