Fig. 3 in Biosynthetic origins of unusual cannabimimetic phytocannabinoids in Cannabis sativa L: A review

Fig. 3. Schematic diagram of phytocannabinoid biosynthesis and precursor pathways. Grey arrows and text indicate putative precursor pathways and enzymes associated with recently reported in planta phytocannabinoid analogues. Coloured arrows and text indicate known biosynthetic pathways leading to the production of phytocannabinoids. Blue arrows and text indicate the methylerythritol phosphate pathway leading to the production of the isoprenoid intermediate geranyl diphosphate used in both monoterpenoid and phytocannabinoid biosynthesis. Red arrows and text indicate the alkylresorcinolic acid pathway leading to the production of the phytocannabinoid intermediate olivetolic acid. Green arrows and text indicate the phytocannabinoid pathway and enzymes leading to the production of monocyclic, dicyclic and tricyclic alkyl phytocannabinoids. Numbers in parentheses indicate compound numbers from Table 1 and their positions indicate putative branch points associated with phytocannabinoid analogue production. Question marks indicate uncertainty over either the transportation of metabolites between subcellular compartments or the catalytic mechanism leading to the biosynthesis of phytocannabinoid metabolites. Biochemical pathway abbreviations: AACT - acetyl-CoA C-acyltransferase (EC 2.3.1.16); ACCase - acetyl-CoA carboxylase (EC 6.4.1.2); ACP - acyl carrier protein; CBC - cannabichromene; CBCAS - cannabichromenic acid synthase; CBD - cannabidiol; CBDAS - cannabidiolic acid synthase (EC:1.21.3.8); CBG - cannabigerol; CMK - 4-(Cytidine 5′-diphospho)-2-C-methyl-Derythritol kinase (EC 2.7.1.148); CoA - coenzyme A; CsAAE1 - acyl-activating enzyme 1; CsOAC - olivetolic acid cyclase (EC:4.4.1.26); CsPT1 - geranylpyrophosphate: olivetolate geranyltransferase (EC 2.5.1.102); CsTKS - tetraketide synthase (EC:2.3.1.206); DMAPP - dimethylallyl diphosphate; DXR - 1-deoxy-D-xylulose-5-phosphate reductoisomerase (EC 1.1.1.267); DXS - 1-deoxy-D-xylulose 5 phosphate synthase (EC 2.2.1.7); ENR - enoyl-ACP reductase; FAD - fatty acid desaturase; FPPS - farnesyl pyrophosphate synthase (EC 2.5.1.10); G3P - glyceraldehyde 3-phosphate; GPPS - geranyl diphosphate synthase (EC:2.5.1.1); HD - 3-hydroxyacyl-ACP dehydratase; HDR - 1-Hydroxy-2-methyl-2-butenyl 4-diphosphate reductase (EC:1.17.7.4); HDS - 1-Hydroxy-2-methyl-2-butenyl 4-diphosphate synthase (EC 1.17.7.3); HMGR - hydroxymethylglutaryl-CoA reductase (EC 1.1.1.34); HMGS - hydroxymethylglutaryl-CoA synthase (EC 2.3.3.10); HPL - hydroperoxide lyase (EC:4.1.2.-); IPP - isopentenyl diphosphate; KAR - 3-ketoacyl-ACP reductase; KAS - β-ketoacyl-ACP synthase; LOX2 - 13S-lipoxygenase 2 (EC:1.13.11.12); MAT - malonyl-CoA: acyl carrier protein malonyltransferase (EC 2.3.1.39); MCT - 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (EC 2.7.7.60); MDS - 2-Cmethyl-D-erythritol 2,4-cyclodiphosphate synthase (EC 4.6.1.12); MEP - methylerythritol phosphate; MK - mevalonate kinase (EC 2.7.1.36); MVA - mevalonate; OPP - diphosphate; PMK - phosphomevalonate kinase (EC 2.7.4.2); PPMD - diphosphomevalonate decarboxylase (EC 4.1.1.33); SCD - stearoyl-CoA desaturase (Delta- 9 desaturase) (EC:1.14.19.1); THC - Δ9 tetrahydrocannabinol; THCAS – Δ9 tetrahydrocannabinolic acid synthase (EC:1.21.3.7); 13(S)-HPODE - 13S-hydroperoxy- 9Z,11E-octadecadienoic acid. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)