Recent advances in cannabinoid biochemistry and biotechnology

Cannabinoids, produced only in Cannabis sativa, are meroterpenoid secondary metabolites composed of monoterpene and polyketide moieties. Numerous cannabinoids have been isolated, and their pharmacological studies and clinical trials have been extensively conducted. Consequently, in recent years, certain formulations containing ∆⁹-tetrahydrocannabinol, the psychoactive principle of marijuana, and its isomer cannabidiol have been approved as prescribed medicines for various refractory diseases in about 30 countries. In addition, recent pioneering studies using a set of biosynthetic genes have enabled synthetic biology and synthetic biochemistry approaches to access plant-derived cannabinoids and new-to-nature analogues without the need for plant breeding. This review introduces the history of cannabinoid biosynthetic studies, and focuses on the biotechnological applications of biosynthetic enzymes.