Molecular activities, biosynthesis and evolution of triterpenoid saponins

Augustin, Jorg; Kuzina, Vera; Andersen, S. B.; Bak, Søren

doi:10.1016/j.phytochem.2011.01.015

Cited by 604 publications

(504 citation statements)

References 243 publications

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“…The general fate of many specialized plant triterpenes like b-amyrin and a-amyrin is to be oxidized multiple times before being glycosylated into the amphipathic molecules called saponins (Moses et al, 2013). Across the plant kingdom, typical saponin glycosylations occur at the C-3 and/or C-28 positions through an O-linkage, implying the significance of the hydroxyl and carboxyl groups at the C-3 and C-28 positions, respectively, in rendering a triterpenoid accessible to UDP-dependent glycosyltransferase reactions (Augustin et al, 2011). CYP716A14v2 oxidizes the C-3 hydroxyl group of triterpenes like b-amyrin and a-amyrin to a carbonyl group and consequently blocks further enzymatic modifications like glycosylation on this position.…”

Section: Terpenoid Biosynthesis Is Differentially Regulated In Trichomentioning

confidence: 99%

OSC2 and CYP716A14v2 Catalyze the Biosynthesis of Triterpenoids for the Cuticle of Aerial Organs of Artemisia annua

et al. 2015

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Section: Terpenoid Biosynthesis Is Differentially Regulated In Trichomentioning

confidence: 99%

OSC2 and CYP716A14v2 Catalyze the Biosynthesis of Triterpenoids for the Cuticle of Aerial Organs of Artemisia annua

et al. 2015

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“…The expression of 8,462 transcripts was visualized by cDNA-AFLP transcript profiling and 282 Methyl JA (MeJA)-responsive tags were identified. The comparable MeJAinduced expression pattern of the genes encoding HMGR, squalene synthase, squalene epoxidase, β-amyrin synthase (BAS) and CYP93E2, enzymes catalyzing steps in triterpene saponin biosynthesis [7][8][9] , indicated co-regulation ( Fig. 1a and Extended Data Fig.…”

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confidence: 96%

“…Notably, application of aliquots of MKB1 KD root culture medium to control roots caused transient tissue loosening (Extended Data Fig. 5b), suggesting that ectopic accumulation of bioactive monoglycosylated saponins [7][8][9]19 and/or other metabolites contributes to the makibishi phenotype and is not a mere consequence of the root defects. These findings suggest that silencing of MKB1 interferes with the biosynthesis of triterpene saponins, which leads to the overaccumulation and release of incompletely glycosylated saponins and correlates with the manifestation of the makibishi phenotype.…”

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confidence: 99%

The protein quality control system manages plant defence compound synthesis

Pollier

Moses

González-Guzmán

et al. 2013

Nature

126

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Jasmonates (JAs) are ubiquitous oxylipin-derived phytohormones that are essential in the regulation of multiple plant processes, encompassing development, growth and defense. Across the plant kingdom, JAs act as elicitors of the production of bioactive secondary metabolites that serve in the defense against attackers 1-3 . Knowledge on the conserved JA perception and early signaling machineries is increasing 3-6 but the downstream mechanisms that regulate defense metabolism remain largely unknown.Here we show that in the model legume Medicago truncatula JA recruits the endoplasmic reticulum-associated degradation (ERAD) quality control system to manage the production of triterpene saponins, widespread bioactive compounds that share a biogenic origin with sterols 7-9 . An ERAD-type RING membrane-anchor (RMA) E3 ubiquitin (Ub)-ligase is co-expressed with saponin synthesis enzymes to control 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the rate-limiting enzyme in the supply of the ubiquitous terpene precursor isopentenyl diphosphate. Thereby unrestrained bioactive saponin accumulation is prevented and plant development and integrity secured. This control apparatus is equivalent to the ERAD system that regulates sterol synthesis in yeasts and mammals but that employs distinct E3 Ub-ligases, of the HMGR Degradation 1 (HRD1)-type, to direct destruction of HMGR 10-13 . Hence, the general principles for management of sterol and triterpene saponin biosynthesis are conserved across eukaryotes but can be controlled by divergent regulatory cues. 3To identify regulators of plant triterpene synthesis, we monitored the transcriptome of suspension-cultured M. truncatula cells, known to accumulate saponins following elicitation with JAs 14 . The expression of 8,462 transcripts was visualized by cDNA-AFLP transcript profiling and 282 Methyl JA (MeJA)-responsive tags were identified. The comparable MeJAinduced expression pattern of the genes encoding HMGR, squalene synthase, squalene epoxidase, β-amyrin synthase (BAS) and CYP93E2, enzymes catalyzing steps in triterpene saponin biosynthesis 7-9 , indicated co-regulation ( Fig. 1a and Extended Data Fig. 1-2). Several genes corresponding to potential regulatory factors had maximal transcriptional upregulation prior to or concurrent with that of the triterpene saponin genes, including a MYC-like bHLH protein and the JAZ repressor proteins, known elements of the core JA signaling module 4-6 , as well as a gene (MT067) corresponding to an RMA-like E3 Ub-ligase 10 , denominated MAKIBISHI1 (MKB1) (Extended Data Fig. 3). The early MeJA response of MKB1 was confirmed in the M. truncatula Gene Expression Atlas (MtGEA; http://bioinfo.noble.org/geneatlas/) 15 (Fig. 1b).To assess MKB1 function, we generated transgenic M. truncatula hairy roots in which MKB1 was overexpressed (MKB1 OE roots) or silenced (MKB1 KD roots) (Extended Data Fig. 4a). MKB1 KD roots showed a striking phenotype, in particular when transferred to liquid medium, which caused 'dissociation' of the MKB1 KD roots into 'c...

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“…These compounds have numerous pharmaceutical, agricultural, and industrial biotechnology applications (2)(3)(4)(5). The ability to harness this diversity to engineer known and new-to-nature triterpenes would therefore be of considerable value.…”

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confidence: 99%

“…Triterpenes, like sterols, are synthesized from the mevalonate pathway via the linear 30-carbon precursor 2,3-oxidosqualene (OS) (Fig. 1A) (2)(3)(4)(5)(6). The first committed step in sterol biosynthesis is cyclization of OS to cycloartenol by cycloartenol synthase.…”

mentioning

confidence: 99%

A conserved amino acid residue critical for product and substrate specificity in plant triterpene synthases

Salmon

Thimmappa

Minto

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Triterpenes are structurally complex plant natural products with numerous medicinal applications. They are synthesized through an origami-like process that involves cyclization of the linear 30 carbon precursor 2,3-oxidosqualene into different triterpene scaffolds. Here, through a forward genetic screen in planta, we identify a conserved amino acid residue that determines product specificity in triterpene synthases from diverse plant species. Mutation of this residue results in a major change in triterpene cyclization, with production of tetracyclic rather than pentacyclic products. The mutated enzymes also use the more highly oxygenated substrate dioxidosqualene in preference to 2,3-oxidosqualene when expressed in yeast. Our discoveries provide new insights into triterpene cyclization, revealing hidden functional diversity within triterpene synthases. They further open up opportunities to engineer novel oxygenated triterpene scaffolds by manipulating the precursor supply.terpenes | natural products | plant defense | cyclization | mutants

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Molecular activities, biosynthesis and evolution of triterpenoid saponins

Cited by 604 publications

References 243 publications

OSC2 and CYP716A14v2 Catalyze the Biosynthesis of Triterpenoids for the Cuticle of Aerial Organs of Artemisia annua

OSC2 and CYP716A14v2 Catalyze the Biosynthesis of Triterpenoids for the Cuticle of Aerial Organs of Artemisia annua

The protein quality control system manages plant defence compound synthesis

A conserved amino acid residue critical for product and substrate specificity in plant triterpene synthases

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