Tetrahydrocannabinolic acid synthase

Structure and Mechanism:

• THCA synthase is a 60 kDa monomeric enzyme with an isoelectric point at 6.4, which can increase to approximately 74 kDa due to post-translational N-linked glycosylation.
• The enzyme’s tertiary structure consists of two domains (I and II) with flavin adenine dinucleotide (FAD) positioned between them.
• THCA synthase catalyzes the oxidative cyclization of the monoterpene moiety of cannabigerolic acid (CBGA) using FAD as a cofactor.
• The reaction involves the transfer of a hydride from CBGA to reduce FAD, leading to the formation of tetrahydrocannabinolic acid (THCA) and hydrogen peroxide (H2O2).

Biological Function:

• THCA synthase is expressed in the glandular trichomes of Cannabis sativa.
• It may contribute to the self-defense mechanism of Cannabis by producing THCA and hydrogen peroxide.
• THCA acts as a necrosis-inducing factor and can convert to THC, the principal psychoactive component of cannabis.
• THC and other cannabinoids have therapeutic effects like reducing nausea, vomiting, and stimulating hunger.

Significance and Production:

• There is a high demand for pharmaceutical-grade THC and cannabinoids due to their therapeutic potential.
• Direct chemical synthesis of THC is challenging, leading to exploration of using THCA synthase for THC production.
• Attempts have been made to produce THCA on a milligram scale in organisms like Pichia pastoris yeast cells.
• Legal regulations on Cannabis cultivation impact the availability of THC and cannabinoids for pharmaceutical use.

Research and Publications:

• Various research papers have been published on THCA synthase, cannabinoid biosynthesis, and related topics.
• Enzymatic production of cannabinoids offers a more sustainable and efficient method compared to traditional chemical synthesis.
• Understanding the stereochemistry of cannabinoid synthesis is crucial for controlling their pharmacological properties.
• The chemical synthesis of cannabinoids involves intricate enzymatic pathways and reactions.

Chemical Synthesis and Applications:

• Chemical synthesis of cannabinoids can be achieved through the enzymatic production of THCA synthase.
• Pichia pastoris has been used as a host organism for producing THCA synthase.
• Enzyme-mediated cannabinoid synthesis offers advantages in terms of purity, yield, and tailored drug development.
• The production of cannabinoids via chemical synthesis presents opportunities for advanced drug development and research.

Tetrahydrocannabinolic acid synthase Data Sources