Assessing Flux Distribution Associated with Metabolic Specialization of Glandular Trichomes

Zager, Jordan J.; Lange, B. Markus

doi:10.1016/j.tplants.2018.04.003

Cited by 21 publications

(15 citation statements)

References 45 publications

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“…5). We recently performed a meta-analysis of gene expression patterns in glandular trichomes across various species (Zager and Lange, 2018). One of the conclusions, consistent with the data presented here, was that gene expression patterns correlate well with the metabolic specialization in these anatomical structures.…”

Section: Coregulation Of Metabolic Pathways In Cannabis Is Consistentsupporting

confidence: 81%

“…Coregulation has been observed for genes across multiple pathways of specialized metabolism, such as cannabinoids and terpenoids (this study), monoterpenes and diterpenes (Salvia pomifera; Trikka et al, 2015), flavonoids and acyl sugars (Salpiglossis sinuata and Solanum quitoense; Moghe et al, 2017), and bitter acids and prenylflavonoids (Humulus lupulus; Kavalier et al, 2011;Clark et al, 2013). These tight gene-to-metabolite correlations were also reflective of predicted fluxes through the relevant pathways (Zager and Lange, 2018). In contrast, gene expression patterns appear to be less predictive of fluxes through central carbon metabolism, where regulation at the protein level plays a more significant role (Paul and Pellny, 2003;Koch, 2004;Gibon et al, 2006;Schwender et al, 2014;Rocca et al, 2015).…”

Section: Coregulation Of Metabolic Pathways In Cannabis Is Consistentmentioning

confidence: 53%

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Gene Networks Underlying Cannabinoid and Terpenoid Accumulation in Cannabis

et al. 2019

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Glandular trichomes are specialized anatomical structures that accumulate secretions with important biological roles in plantenvironment interactions. These secretions also have commercial uses in the flavor, fragrance, and pharmaceutical industries. The capitate-stalked glandular trichomes of Cannabis sativa (cannabis), situated on the surfaces of the bracts of the female flowers, are the primary site for the biosynthesis and storage of resins rich in cannabinoids and terpenoids. In this study, we profiled nine commercial cannabis strains with purportedly different attributes, such as taste, color, smell, and genetic origin. Glandular trichomes were isolated from each of these strains, and cell type-specific transcriptome data sets were acquired. Cannabinoids and terpenoids were quantified in flower buds. Statistical analyses indicated that these data sets enable the high-resolution differentiation of strains by providing complementary information. Integrative analyses revealed a coexpression network of genes involved in the biosynthesis of both cannabinoids and terpenoids from imported precursors. Terpene synthase genes involved in the biosynthesis of the major monoterpenes and sesquiterpenes routinely assayed by cannabis testing laboratories were identified and functionally evaluated. In addition to cloning variants of previously characterized genes, specifically CsTPS14CT [(2)-limonene synthase] and CsTPS15CT (b-myrcene synthase), we functionally evaluated genes that encode enzymes with activities not previously described in cannabis, namely CsTPS18VF and CsTPS19BL (nerolidol/linalool synthases), CsTPS16CC (germacrene B synthase), and CsTPS20CT (hedycaryol synthase). This study lays the groundwork for developing a better understanding of the complex chemistry and biochemistry underlying resin accumulation across commercial cannabis strains.

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Section: Coregulation Of Metabolic Pathways In Cannabis Is Consistentsupporting

confidence: 81%

Section: Coregulation Of Metabolic Pathways In Cannabis Is Consistentmentioning

confidence: 53%

Gene Networks Underlying Cannabinoid and Terpenoid Accumulation in Cannabis

et al. 2019

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“…Analysis of leaf surface extracts indicated the resin from each species contained the diterpenoids of interest (Additional file 2: Figure S1). Furthermore, analysis of the trichome-enriched transcriptomes indicated a high level of activity of the MEP pathway based on TPM values (Additional file 1: Table S2), which is generally known to be involved in diterpenoid biosynthesis [68]. Taken together with the identification of the presently reported diTPSs and CPTs, it is likely that the trichomes are the site of diterpenoid biosynthesis in the Eremophila species examined here.…”

Section: Involvement Of Trichomes In the Biosynthesis Of Diterpenoidsmentioning

confidence: 65%

Nerylneryl diphosphate is the precursor of serrulatane, viscidane and cembrane-type diterpenoids in Eremophila species

et al. 2020

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Background: Eremophila R.Br. (Scrophulariaceae) is a diverse genus of plants with species distributed across semi-arid and arid Australia. It is an ecologically important genus that also holds cultural significance for many Indigenous Australians who traditionally use several species as sources of medicines. Structurally unusual diterpenoids, particularly serrulatane and viscidane-types, feature prominently in the chemical profile of many species and recent studies indicate that these compounds are responsible for much of the reported bioactivity. We have investigated the biosynthesis of diterpenoids in three species: Eremophila lucida, Eremophila drummondii and Eremophila denticulata subsp. trisulcata. Results: In all studied species diterpenoids were localised to the leaf surface and associated with the occurrence of glandular trichomes. Trichome-enriched transcriptome databases were generated and mined for candidate terpene synthases (TPS). Four TPSs with diterpene biosynthesis activity were identified: ElTPS31 and ElTPS3 from E. lucida were found to produce (3Z,7Z,11Z)-cembratrien-15-ol and 5-hydroxyviscidane, respectively, and EdTPS22 and EdtTPS4, from E. drummondii and E. denticulata subsp. trisulcata, respectively, were found to produce 8,9-dihydroserrulat-14-ene which readily aromatized to serrulat-14-ene. In all cases, the identified TPSs used the cisoid substrate, nerylneryl diphosphate (NNPP), to form the observed products. Subsequently, cis-prenyl transferases (CPTs) capable of making NNPP were identified in each species. Conclusions: We have elucidated two biosynthetic steps towards three of the major diterpene backbones found in this genus. Serrulatane and viscidane-type diterpenoids are promising candidates for new drug leads. The identification of an enzymatic route to their synthesis opens up the possibility of biotechnological production, making accessible a ready source of scaffolds for further modification and bioactivity testing.

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“…We have previously employed mathematical modeling as a tool for formulating hypotheses concerning GT metabolism in silico, thereby reducing the number of follow-up experiments required for testing the strongest hypotheses ( Rios-Estepa et al, 2008 , 2010 ; Lange and Rios-Estepa, 2014 ; Johnson et al, 2017 ; Zager and Lange, 2018 ; Turner et al, 2019 ). To apply this methodology to this study, we developed a genome-scale model (termed Solyc_tVI-GT_2021v1) of metabolism in tVI-GTs of tomato, which incorporates publicly available information and several datasets acquired as part of this study (details describing the model development process are provided in Supplemental Methods and Data File S1 ).…”

Section: Resultsmentioning

confidence: 99%

Flavonoid deficiency disrupts redox homeostasis and terpenoid biosynthesis in glandular trichomes of tomato

et al. 2021

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Glandular trichomes are epidermal structures that provide a first line of chemical defense against arthropod herbivores and other biotic threats. The most conspicuous structure on leaves of cultivated tomato (Solanum lycopersicum) is the type-VI glandular trichome (tVI-GT), which accumulates both flavonoids and volatile terpenoids. Although these classes of specialized metabolites are derived from distinct metabolic pathways, previous studies with a chalcone isomerase 1 (CHI1)-deficient mutant called anthocyanin free (af) showed that flavonoids are required for terpenoid accumulation in tVI-GTs. Here, we combined global transcriptomic and proteomic analyses of isolated trichomes as a starting point to show that the lack of CHI1 is associated with reduced levels of terpenoid biosynthetic transcripts and enzymes. The flavonoid deficiency in af trichomes also resulted in the upregulation of abiotic stress-responsive genes associated with DNA damage and repair. Several lines of biochemical and genetic evidence indicate that the terpenoid defect in af mutants is specific for the tVI-GT and is associated with the absence of bulk flavonoids rather than loss of CHI1 per se. A newly developed genome-scale model of metabolism in tomato tVI-GTs helped identify metabolic imbalances caused by the loss of flavonoid production. We provide evidence that flavonoid deficiency in this cell type leads to increased production of reactive oxygen species (ROS), which may impair terpenoid biosynthesis. Collectively, our findings support a role for flavonoids as ROS-scavenging antioxidants in glandular trichomes.

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Assessing Flux Distribution Associated with Metabolic Specialization of Glandular Trichomes

Cited by 21 publications

References 45 publications

Gene Networks Underlying Cannabinoid and Terpenoid Accumulation in Cannabis

Gene Networks Underlying Cannabinoid and Terpenoid Accumulation in Cannabis

Nerylneryl diphosphate is the precursor of serrulatane, viscidane and cembrane-type diterpenoids in Eremophila species

Flavonoid deficiency disrupts redox homeostasis and terpenoid biosynthesis in glandular trichomes of tomato

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