## 2 Results
### Metabolic Profiles of Cultivars  
Furthermore, the gene expressions of the metabolic enzymes were compared among the cultivars to elucidate their relative production capacities. Most genes in the core central metabolism, as well as MEP and MVA pathways, were highly expressed in the WS cultivar, unlike others, suggesting that it has the highest NADPH and carbon feedstock productivities (Figure 4a). Consistently, the WS cultivar also had one of the lowest gene expressions for the PEPC enzyme, thus enabling it to redirect phosphoenolpyruvate to pyruvate feedstock production. Additionally, in the WS cultivar, the low gene expression for PDC and ALDH enzymes that drive NADH production (Figure 2c) may be compensated by high CS expression replenishing the TCA cycle to make the cofactors. Similarly, the high expression of CS and _ME_ (_NADP+_) in WS may make up for its relatively low _GAPN_ expression in producing NADPH. On the other hand, the HB cultivar seemed to excel in NADPH production via the up-regulation of both _GAPN_ and _ME_ (_NADP+_) genes, but was partly offset by its lower _CS_ expression level compared to the WS cultivar. The WS cultivar also had broadly higher gene expressions in the hexanoate pathway (Figure 4a), suggesting its larger upstream capacity for cannabinoid production. In this regard, its lower _ALDH_ level could already be sufficient for generating the required hexanoic acid for synthesizing cannabinoids (Figure 3a). Both the WS and CD cultivars also had some of the highest transcript abundances for APT, THCAS, and CBDAS enzymes but were still somewhat matched by the HB cultivar for THCAS and by the GT cultivar for CBDAS. Notably, the TH cultivar showed relatively low gene expression levels across all metabolic pathways (Figure 4a).  
Expectedly, the gene expression for five major TPSs, namely, myrcene synthase (MYS), limonene synthase (LS), \(\alpha\)-humulene synthase (\(\alpha\)HS), meridold synthase (NES), and germacrene A synthase (GAS), were significantly up-regulated in the trichomes compared to the stem (Figure 3b and Figure S4). The CD cultivar had the highest total transcript levels for _LS_ (TMM = 1.87 \(\times\) 10\({}^{6}\)) and _NES_ (6.58 \(\times\) 10\({}^{4}\)), which were about twice those of the TH cultivar with the lowest expression (TMM = 9.66 \(\times\) 10\({}^{5}\) and 3.32 \(\times\) 10\({}^{4}\), respectively) (Figure 4b). On the other hand, the WS cultivar had the highest gene expression for _MYS_, \(\alpha\)HS, and _GAS_.  
As no chemical profiling data were available for rationalizing the metabolic outputs based on gene expression, publicly available information was used for the few comparisons that were possible (Table S7). Although THC levels were indeed higher in both WS and CD cultivars compared to others, as would be expected from their _THCAS_ expression (Figure 4a), the levels of cannabinoids were, however, not in line with the relative gene expression of _THCAS_ in WS and CD. CBDA and \(\beta\)-myrcene were also expectedly higher in WS compared to CD, based on respective _CBDAS_ and _MYS_ expressions (Figure 4b). On the other hand, the relative levels of limonene in WS and CD cultivars were inconsistent with the relative expressions of _LS_ in the two cultivars.