Advancement of Research Progress on Synthesis Mechanism of Cannabidiol (CBD)

Abstract

Cannabis sativa L. is a multipurpose crop with high value for food, textiles, and other industries. Its secondary metabolites, including cannabidiol (CBD), have potential for broad application in medicine. With the CBD market expanding, traditional production may not be sufficient. Here we review the potential for the production of CBD using biotechnology. We describe the chemical and biological synthesis of cannabinoids, the associated enzymes, and the application of metabolic engineering, synthetic biology, and heterologous expression to increasing production of CBD.

Keywords: Cannabidiol (CBD); biosynthesis; cannabinoid; metabolic engineering; synthetic biology.

Figure 1

Endocannabinoid system. Anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) are two major endogenous cannabinoids. ECS is distributed throughout the human body and regulates the energy balance of the human central nervous system and peripheral nerve metabolism. It is related to many physiological functions such as appetite digestion, emotion, inflammation and pain response, immune function, temperature regulation and so on.

Figure 2

(−)-CBD and (+)-CBD molecular structures

Figure 3

Molecular formulas of several important cannabinoids and their acids.

Figure 4

Biosynthesis pathway of cannabinoids.

Figure 5

CBD chemical synthesis scheme. (A) p-TsCl = para-toluenesulfonyl chloride. (B) Stereoselective synthesis of (−)-CBD. (C) Kobayashi ’s CBD synthesis scheme. TMEDA = tetramethylethylenediamine, DBHQ = 2,5-di-tert-butylhydroquinone, py = pyridine, and THF = tetrahydrofuran. (D) DCC = N,N′-dicyclohexylcarbodiimide, DMAP = 4-dimethylaminopyridine, KHMDS = potassium bis(trimethylsilyl) amide, and TMSCl = chlorotrimethylsilane.