GAME9 regulates the biosynthesis of steroidal alkaloids and upstream isoprenoids in the plant mevalonate pathway

Cárdenas, Pablo D.; Sonawane, Prashant; Pollier, Jacob; Bossche, Robin Vanden; Dewangan, Veena; Weithorn, Efrat; Tal, Lior; Meir, Sagit; Rogachev, Ilana; Malitsky, Sergey; Giri, Ashok P.; Goossens, Alain; Burdman, Saul; Aharoni, Asaph

doi:10.1038/ncomms10654

Cited by 271 publications

(299 citation statements)

References 63 publications

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“…In a recent example, Cárdenas et al (2016) demonstrated that an AP2-type transcription factor (GLYCOALKALOID METABOLISM9 [GAME9]) could likely activate genes of the clustered steroidal glycoalkaloid pathway genes such as GAME4. Yet, GAME9 is located on chromosome 1 and hence is not physically associated with the steroidal glycoalkaloid cluster genes situated on chromosomes 7 and 12 in tomato and potato (Solanum tuberosum).…”

Section: Common and Unique Features Of The B-diketone Metabolic Genementioning

confidence: 99%

A Metabolic Gene Cluster in the Wheat W1 and the Barley Cer-cqu Loci Determines β-Diketone Biosynthesis and Glaucousness

et al. 2016

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The glaucous appearance of wheat (Triticum aestivum) and barley (Hordeum vulgare) plants, that is the light bluish-gray look of flag leaf, stem, and spike surfaces, results from deposition of cuticular b-diketone wax on their surfaces; this phenotype is associated with high yield, especially under drought conditions. Despite extensive genetic and biochemical characterization, the molecular genetic basis underlying the biosynthesis of b-diketones remains unclear. Here, we discovered that the wheat W1 locus contains a metabolic gene cluster mediating b-diketone biosynthesis. The cluster comprises genes encoding proteins of several families including type-III polyketide synthases, hydrolases, and cytochrome P450s related to known fatty acid hydroxylases. The cluster region was identified in both genetic and physical maps of glaucous and glossy tetraploid wheat, demonstrating entirely different haplotypes in these accessions. Complementary evidence obtained through gene silencing in planta and heterologous expression in bacteria supports a model for a b-diketone biosynthesis pathway involving members of these three protein families. Mutations in homologous genes were identified in the barley eceriferum mutants defective in b-diketone biosynthesis, demonstrating a gene cluster also in the b-diketone biosynthesis Cer-cqu locus in barley. Hence, our findings open new opportunities to breed major cereal crops for surface features that impact yield and stress response.

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Section: Common and Unique Features Of The B-diketone Metabolic Genementioning

confidence: 99%

A Metabolic Gene Cluster in the Wheat W1 and the Barley Cer-cqu Loci Determines β-Diketone Biosynthesis and Glaucousness

et al. 2016

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“…Op ERF2 was assigned to the clade that is composed of group IX ERFs, with the members previously reported to be involved in specialized metabolism. Interestingly, Op ERF2 exhibited a closer relationship with C. roseus ORCA2 and ORCA3 that regulate MIA biosynthesis than with Sl JRE4, Nb ERF1, Nt ERF189, and Nt ORC1, the ERFs from Solanaceae family that regulate SGA and nicotine alkaloids biosynthesis (van der Fits and Memelink, 2000, 2001; Shoji et al, 2010; Todd et al, 2010; Cárdenas et al, 2016; Thagun et al, 2016) or Aa ERF1 and Aa ERF2 from Asteraceae family that regulate terpenoid biosynthesis (Yu et al, 2012). Op ERF4 and Op ERF5 were classified into a separated cluster that exclusively consists of Arabidopsis group IXc ERFs.…”

Section: Resultsmentioning

confidence: 99%

“…Among them, Cr ORCA2 and Cr ORCA3 are classified as APETHALA2/Ethylene Response Factor (AP2/ERF). AP2/ERF represents a superfamily of transcription factor that plays an important role in plant biological systems, such as growth and development (Chuck et al, 1998; Ohto et al, 2009), response to stimuli (Licausi et al, 2010; Mizoi et al, 2012; Zhao et al, 2012), and biosynthesis of primary and secondary metabolites (van der Fits and Memelink, 2000, 2001; Zhang et al, 2005; Shoji et al, 2010; Todd et al, 2010; Cárdenas et al, 2016; Thagun et al, 2016). On the basis of the number of conserved AP2/ERF domain and the existence of a family-specific B3 domain, AP2/ERFs are further classified into three families: AP2, ERF, and RAV.…”

Section: Introductionmentioning

confidence: 99%

“…A cluster of ERFs in the NIC2 locus of Nicotiana tabacum control nicotine biosynthesis in tobacco (Shoji et al, 2010). Recently, the orthologs of GAME9/JRE4 were reported to modulate steroidal glycoalkaloids (SGA) in tomato and potato (Cárdenas et al, 2016; Thagun et al, 2016). Aa ERF1 and Aa ERF2 from Artemisia annua L. positively regulate artemisinin biosynthesis (Yu et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Function of AP2/ERF Transcription Factors Involved in the Regulation of Specialized Metabolism in Ophiorrhiza pumila Revealed by Transcriptomics and Metabolomics

et al. 2016

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The hairy roots (HR) of Ophiorrhiza pumila produce camptothecin (CPT), a monoterpenoid indole alkaloid used as a precursor in the synthesis of chemotherapeutic drugs. O. pumila HR culture is considered as a promising alternative source of CPT, however, the knowledge about the biosynthetic pathway and regulatory mechanism is still limited. In this study, five genes that encode AP2/ERF transcription factors, namely OpERF1–OpERF5, were isolated from HR of O. pumila. Phylogenetic analysis of AP2/ERF protein sequences suggested the close evolutionary relationship of OpERF1 with stress-responsive ERF factors in Arabidopsis and of OpERF2 with ERF factors reported to regulate alkaloid production, such as ORCA3 in Catharanthus roseus, NIC2 locus ERF in tobacco, and JRE4 in tomato. We generated the transgenic HR lines of O. pumila, ERF1i and ERF2i, in which the expression of OpERF1 and OpERF2, respectively, was suppressed using RNA interference technique. The transcriptome and metabolome of these suppressed HR were analyzed for functional characterization of OpERF1 and OpERF2. Although significant changes were not observed in the metabolome, including CPT and related compounds, the suppression of OpERF2 resulted in reduced expression of genes in the 2-C-methyl-d-erythritol 4-phosphate and secologanin-strictosidine pathways, which supply a precursor, strictosidine, for CPT biosynthesis. Furthermore, while it was not conclusive for OpERF1, enrichment analysis of differentially expressed genes in the suppressed HR showed that the gene ontology terms for oxidation-reduction, presumably involved in secondary metabolite pathways, were enriched in the ERF2i downregulated gene set. These results suggest a positive role of OpERF2 in regulating specialized metabolism in O. pumila.

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“…Notably, unlike other plants, Solanaceae plant species also accumulate cholesterol as a major sterol [56, 57]. The biosynthesis of cholesterol in Solanaceae has not been elucidated yet, but was shown to involve a sterol side chain reductase enzyme (SSR) 2 that catalyzes the conversion of cycloartenol into cycloartanol by reduction of the C-24(25) double bond.…”

Section: Resultsmentioning

confidence: 99%

Cloning and Functional Characterization of Cycloartenol Synthase from the Red Seaweed Laurencia dendroidea

et al. 2016

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The red seaweed Laurencia dendroidea belongs to the Rhodophyta, a phylum of eukaryotic algae that is widely distributed across the oceans and that constitute an important source of bioactive specialized metabolites. Laurencia species have been studied since 1950 and were found to contain a plethora of specialized metabolites, mainly halogenated sesquiterpenes, diterpenes and triterpenes that possess a broad spectrum of pharmacological and ecological activities. The first committed step in the biosynthesis of triterpenes is the cyclization of 2,3-oxidosqualene, an enzymatic reaction carried out by oxidosqualene cyclases (OSCs), giving rise to a broad range of different compounds, such as the sterol precursors cycloartenol and lanosterol, or triterpene precursors such as cucurbitadienol and β-amyrin. Here, we cloned and characterized the first OSC from a red seaweed. The OSC gene was identified through mining of a L. dendroidea transcriptome dataset and subsequently cloned and heterologously expressed in yeast for functional characterization, which indicated that the corresponding enzyme cyclizes 2,3-oxidosqualene to the sterol precursor cycloartenol. Accordingly, the gene was named L. dendroidea cycloartenol synthase (LdCAS). A phylogenetic analysis using OSCs genes from plants, fungi and algae revealed that LdCAS grouped together with OSCs from other red algae, suggesting that cycloartenol could be the common product of the OSC in red seaweeds. Furthermore, profiling of L. dendroidea revealed cholesterol as the major sterol accumulating in this species, implicating red seaweeds contain a ‘hybrid’ sterol synthesis pathway in which the phytosterol precursor cycloartenol is converted into the major animal sterol cholesterol.

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GAME9 regulates the biosynthesis of steroidal alkaloids and upstream isoprenoids in the plant mevalonate pathway

Cited by 271 publications

References 63 publications

A Metabolic Gene Cluster in the Wheat W1 and the Barley Cer-cqu Loci Determines β-Diketone Biosynthesis and Glaucousness

A Metabolic Gene Cluster in the Wheat W1 and the Barley Cer-cqu Loci Determines β-Diketone Biosynthesis and Glaucousness

Function of AP2/ERF Transcription Factors Involved in the Regulation of Specialized Metabolism in Ophiorrhiza pumila Revealed by Transcriptomics and Metabolomics

Cloning and Functional Characterization of Cycloartenol Synthase from the Red Seaweed Laurencia dendroidea

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