# Phytocannabinoids Biosynthesis in Angiosperms, Fungi, and Liverworts and Their Versatile Role
## 1 Introduction  
Phytocannabinoids are meroterpenoids bearing a resorcinol core with an isoprenyl, alkyl, oralkyl para-positioned side chain, or alkyl group usually containing an odd number of carbon atoms--cannabinoids that have an even number of carbon atoms in the side chain are rare. Phytocannabinoids can be obtained from angiosperms (flowering plants), fungi, and liverworts (Figure 1). The first phytocannabinoid was isolated from the _Cannabis sativa_ family Cannabaceae, but it has a long controversial history of its use and abuse [1, 2]. From _C. sativa_ more than 113 phytocannabinoids were isolated and classified into several groups such as cannabinoids (CBDs), cannabigerols (CBGs), cannabigerols (CBLs), cannabigerols (CBNs), cannabinoids (CBNs), cannabinoids (CBNs), cannabichromes (CBRs), (\(-\))-\(\Delta^{9}\)_trans_-tetrahydroocannabin (\(\Delta^{9}\)-THC) and miscellaneous cannabinoids [1, 3, 4, 5]. Compounds obtained from _C. sativa_ predomtimately generate alkyl-type phytocannabinoids with a monoterpene isoprenyl and the pentyl side chain [4, 6]. In _C. sativa_, CBD, CBG, CBC, cannabichromeverine (CBCV), and \(\Delta^{9}\)-THC are the most abundant cannabinoids in their respective acidic form. The acidic form of the cannabi-noid (C22, \"pre-cannabinoids\") is the final step of the cannabinoid biosynthetic pathway. Oxidation, decarboxylation, and cyclization lead to the development of modified phytocannabinoid via spontaneous breakdown or conversion product. The conversion mainly occurs due to the poor oxidative stability of phytocannabinoids, especially with the alkyl group. _C. sativa_ produces the most common phytocannabinoids. In addition to this, thebrains of mammals have receptors that respond to the _C. sativa_ cannabinoid, so they were termed as cannabinoid receptor types 1 and 2 (CB\({}_{1}\)R and CB\({}_{2}\)R) and thus participated in the endocannabinoid system [1; 3; 4; 7; 8]. The Endocannabinoid system in humans and animals revealed that it participates in the regulation of biological functions such as memory, brain system, mood and addiction along with cellular and metabolic processes such as glycolysis, lipolysis, and the energy balance system [7; 9]. Other angiosperms such as _Helichrysum umbraculigerun_ (Asteraceae) native to South Africa, _Amorpha friticosa_ (Fabaceae), and _Glycyrrhiza foetida_ (Fabaceae) contains a bioactive compound bearing a cannabinoid backbone (Figure 2); they are characterized as prenylated biphenyl derivatives because the aralkyl side chain occurs [1; 10]. Many _Rhododendron_ species (family Ericaceae) such as _Rh. dauticum_ native to Northeastern Asia, _Rh. adamsii_ found in Eastern Siberia and Mongolia, _Rh. rubiginosum_ var. _rubiginosum_ native to Southwest China, and _Rh. anthropogonoides_ grown in Southern China, all generate active monoter  
Figure 1: Structure of phytocannabinoids in _Cannabis sativa_. Abbreviations: CBC, cannabichromene; CBCA, cannabichromene acid; CBCV, cannabichromeraine; CBCVA, cannabichromevarinic acid; CBD, cannabidici; CBD, cannabidici acid; CBDV, cannabidiciure, CBE, cannabidicious; CBG, cannabigerol; CBL, cannabicylod; A\({}^{8}\)-THC, \(\Delta^{8}\)-tetrahydrocannabinol; A\({}^{9}\)-THC, \(\Delta^{9}\)-tetrahydrocannabinol; A\({}^{9}\)-THC, \(\Delta^{9}\)-tetrahydrocannabinolic acid; A\({}^{9}\)-THCV, \(\Delta^{9}\)-tetrahydrocannabivarinic acid. Figure 2: Structure of phytocannabinoids in _Helichrysum_ and _Glycyrrhiza_ plants. are CBC types with an orcinol or methyl group side chain (Figure 3). _Rh. dauricum_ particularly produces cannabinoids bearing sesquiterpene moiety such as daurichromic acid (DCA), gifidic acid (GFA), confluentin, and rhododaurichromenic acid [11; 12; 13]. _Rh. adamsii_ produces cannabigerorcinic acid, DCA, cannabigerorcinic acid methylase, chromosome, and chromene monoterpenoids; _Rh. rubiginosum_ produces cannabinoid rubiginos A-G [14; 15]. _Rh.