Comparative Transcriptome Analysis Reveals Coordinated Transcriptional Regulation of Central and Secondary Metabolism in the Trichomes of Cannabis Caluvars  
[PERSON]  
1 Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore; [EMAIL_ADDRESS] (H.C.Y. ); [EMAIL_ADDRESS] (V.A.R. ); [EMAIL_ADDRESS] (B.-G.M. ); [EMAIL_ADDRESS] (S.H.L. ); [EMAIL_ADDRESS] (S.D.) [PERSON]  
1 Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore; [EMAIL_ADDRESS] (H.C.Y. ); [EMAIL_ADDRESS] (V.A.R. ); [EMAIL_ADDRESS] (B.-G.M. ); [EMAIL_ADDRESS] (S.H.L. ); [EMAIL_ADDRESS] (S.D.) [PERSON]  
1 Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore; [EMAIL_ADDRESS] (H.C.Y. ); [EMAIL_ADDRESS] (V.A.R. ); [EMAIL_ADDRESS] (B.-G.M. ); [EMAIL_ADDRESS] (S.H.L. ); [EMAIL_ADDRESS] (S.D.) [PERSON]  
1 Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore; [EMAIL_ADDRESS] (H.C.Y. ); [EMAIL_ADDRESS] (V.A.R. ); [EMAIL_ADDRESS] (B.-G.M. ); [EMAIL_ADDRESS] (S.H.L. ); [EMAIL_ADDRESS] (S.D.) [PERSON]  
1 Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore; [EMAIL_ADDRESS] (H.C.Y. ); [EMAIL_ADDRESS] (V.A.R. ); [EMAIL_ADDRESS] (B.-G.M. ); [EMAIL_ADDRESS] (S.H.L. ); [EMAIL_ADDRESS] (S.D.) 2 Department of Biological Sciences, National University of Singapore, Singapore  
increased demand, which provides further impetus for developing crops with desired cannabinoid profiles. Cannabinoid biosynthesis mainly occurs in the glandular trichome of female Cannabis infloresresences. Subcellularly, the pathway starts in the cytosol, where the precursor, hexanoic acid, is derived from the oxidative cleavage of fatty acids, such as palmitic acid, by an acylactivating enzyme (AAE) to form hexanoyl coenzyme A. The latter is then biochemically combined with three malonyl coenzyme A molecules by Olivetol synthase and olivetolic acid cyclase (OAC) to form olivetolic acid (OA) [4]. Following this, the acid is prenylated to form cannabinoid acid (CBGA) as the starting cannabinoid, using geranyl diphosphate (GPP) made via the chloroplastic MEP pathway [5]. Subsequent oxidative cyclization of CBGA in the resin cavity results in the production of various other cannabinoids [6]. Notably, the cannabinoids, tetrahydroocannabinolic acid (THCA) and cannabidiolic acid (CBDA), can also be decarboxylated by heating to produce THC and CBD, respectively [7]. In all, close to 120 cannabinoids have been identified [8; 9], in 10 categories: (\(-\))-\(\Delta^{8}\)_-trans_-tetrahydrocannabinols (\(\Delta^{8}\)-THC), (\(-\))-\(\Delta^{9}\)_-trans_-tetrahydrocannabinols (\(\Delta^{9}\)-THC), CBD, cannabitorids (CBT), cannabigerols (CBG), cannabionols (CBN), cannabicyclols (CBL), cannabiondiols (CBND), cannabichromenes (CBC), and cannabileSOs (CBE) [10]. Although several cannabinoid biosynthetic enzymes have been identified [11; 12; 13], the genetics underlying their diversity in the plant remains poorly understood [14]. Similarly, terpen are also biosynthesized and stored in large amounts in the glandular trichome of female Cannabis infloresences. Some common terpen produced by Cannabis include the monoterenes, (R)-linal, \(\alpha\)-pinene, and limonene, as well as the sesquiterpenes, bisabolol, (E)-\(\beta\)-farnesene, \(\beta\)-caryophyllene, and \(\alpha\)-humulene [15]. Some are thought to interact with cannabinoids and regulate or change their physiological effects [16]. As a result, such 'entourage effect' also modulates the medicinal uses of Cannabis plants [17]. For example, \(\beta\)-caryophyllene can be used as a dietary supplement due to its ability to enhance binding to the CB2 cannabinoid receptor, thus reducing gastrointestinal inflammation [18].