Genomic description of critical upstream cannabinoid biosynthesis genes

Abstract

Cannabinoid production is one of the key attributes of the plant Cannabis sativa and the characterization of the genes involved is an essential first step to develop tools for their optimization. We used bioinformatic approaches to annotate and explore variation in the coding genes for critical enzymes comprising the cannabinoid pathway: Olivetol Synthase (OLS), Olivetolic Acid Cyclase (OAC), and Cannabigerolic Acid Synthase (CBGAS), in multiple C. sativa genomes. These upstream genes of the Cannabinoid Oxidocyclase Genes THCAS, CBDAS, and CBCAS generate the necessary precursor molecules to produce the cannabinoids THC and CBD. We found that these genes vary in copy number and confirm that OLS, OAC, CBGAS, and the Cannabinoid Oxidocyclases are on separate chromosomes, while homologs are found in proximity. CBGAS, located on Chromosome X, suggests potential dosage effects in female plants. Except for the Cannabinoid Oxidocyclase genes, the other genes have multiple exons, up to 10 in CBGAS. Through differential exon usage explorations in CBGAS we found evidence for potential regulatory differences. This study provides valuable insight on the genomic identity and variation of cannabinoid biosynthesis genes that will benefit future research on the origin and evolution of this pathway, driver of economic, social, and medicinal value.

Cannabis sativa: Applications of Artificial Intelligence AI and Plant Tissue Culture for Micropropagation

“…Cannabis sativa L. is a wind-pollinated, dioecious medicinal plant (i.e., the male and female reproductive structures are on separate plants), although monoecious plants (male and female flowers on same plant) can occur in some population (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Male plants die shortly after flowering.…”

“…Male plants die shortly after flowering. The female plants live 3 to 5 weeks until seed is fully riped (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Therefore, the plants are obligatory out-crossers.…”

“…Therefore, the plants are obligatory out-crossers. In commercial production, medical Cannabis (drug or marijuana type) plants are all genetically female and male plants are destroyed as seed formation reduces flower quality (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Additionally, the species Cannabis sativa L. and Cannabis indica are a potential source of fibre, food, oil, and protein.…”

“…However, cannabis research work remains years behind than other crops because of the long legacy of prohibition and stigmatization. Cannabis is the most commonly used illicit drug worldwide and the active constituents of the product were described several decades ago (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). The legal status of Cannabis is changing, fuelling an increasing diversity of Cannabis derived products (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

“…Cannabis is the most commonly used illicit drug worldwide and the active constituents of the product were described several decades ago (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). The legal status of Cannabis is changing, fuelling an increasing diversity of Cannabis derived products (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). New laws leading to decriminalization and legalization have given rise to a global, multibillion dollar industry that is projected to continue to grow (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)…”