A Single Oxidosqualene Cyclase Produces the <i>Seco</i>-Triterpenoid α-Onocerin

Almeida, Aldo; Dong, Lemeng; Khakimov, Bekzod; Bassard, Jean‐Etienne; Moses, Tessa; Lota, Frédéric; Goossens, Alain; Appendino, Giovanni; Bak, Søren

doi:10.1104/pp.17.01369

Cited by 20 publications

(11 citation statements)

References 56 publications

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“…Recent work in Ononis spinosa OSC found that by using 2,3-oxidosqualene dioxide with epoxide groups on either end, the hydroxylated intermediate is able to re-enter the active site for hydroxylation of the second epoxide ring to give α-onocerin, implying conformational changes in the active site to accommodate the intermediate [31]. Protein flexibility is very crucial, as it can compensate for errors in the homology models, as well as allow ligands to bind to the active site [28].…”

Section: Resultsmentioning

confidence: 99%

Tuscan Varieties of Sweet Cherry Are Rich Sources of Ursolic and Oleanolic Acid: Protein Modeling Coupled to Targeted Gene Expression and Metabolite Analyses

et al. 2019

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The potential of six ancient Tuscan sweet cherry (Prunus avium L.) varieties as a source of health-promoting pentacyclic triterpenes is here evaluated by means of a targeted gene expression and metabolite analysis. By using a sequence homology criterion, we identify five oxidosqualene cyclase genes (OSCs) and three cytochrome P450s (CYP85s) that are putatively involved in the triterpene production pathway in sweet cherries. We performed 3D structure prediction and induced-fit docking using cation intermediates and reaction products for some OSCs to predict their function. We show that the Tuscan varieties have different amounts of ursolic and oleanolic acids and that these variations are related to different gene expression profiles. This study stresses the interest of valorizing ancient fruits as alternative sources of functional molecules with nutraceutical value. It also provides information on sweet cherry triterpene biosynthetic genes, which could be the object of follow-up functional studies.

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Section: Resultsmentioning

confidence: 99%

Tuscan Varieties of Sweet Cherry Are Rich Sources of Ursolic and Oleanolic Acid: Protein Modeling Coupled to Targeted Gene Expression and Metabolite Analyses

et al. 2019

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“…Considering the size of the deduced protein sequence, it is possible that GgSQE4 represents a partial CDS. Three putative G. glabra epoxidase enzymes (GgSQE2, GgSQE3 and GgSQE4) were 90–96% homologous to the characterised Ononis spinosa SQE enzyme (AUD09558.1), which is involved in seco -triterpenoid biosynthesis (Almeida et al 2018 ) (Table 1 ). While GgSQE1 was found homologs (89%) to Astragalus membranaceus (AHY94896.1 and AKO83630.1) with a role in triterpenoid biosynthesis, GgSQE5 was 76% homologous to Arabidopsis thaliana squalene epoxidase 3 enzyme (AT4G37760) important for embryo development (Laranjeira et al 2015 ).…”

Section: Resultsmentioning

confidence: 99%

Transcriptome-wide identification of squalene epoxidase genes from Glycyrrhiza glabra L.: expression analysis and heterologous expression of GgSQE1 suggest important role in terpenoid biosynthesis

et al. 2021

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Squalene epoxidase (SQE) is a crucial regulatory enzyme for the biosynthesis of several important classes of compounds including sterols and triterpenoids. The present paper identified and characterised five SQE genes ( GgSQE1 to GgSQE5 ) from Glycyrrhiza glabra through transcriptome data mining and homology-based cloning, for the first time . The phylogenetic analysis implied their functional divergence . The ORF corresponding to one of the five SQEs, namely, GgSQE1 , was cloned and studied for its function in a heterologous system, following transient and stable expressions. The transient expression followed by Gg SQE1 encoding protein purification suggested approximately 58.0-kDa protein following the predicted molecular mass of the deduced protein. The gene expression profiling based on qRT-PCR indicated its highest expression (6.4-folds) in the 10-month-old roots. Furthermore, ABA (12.4-folds) and GA 3 (2.47) treatments upregulated the expression of GgSQE1 in the shoots after 10 and 12 hours, respectively, which was also reflected in glycyrrhizin accumulation. The inductive effects of ABA and GA 3 over GgSQE1 expression were also confirmed through functional analysis of GgSQE1 promoters using GUS fusion construct. Stable constitutive expression of GgSQE1 in Nicotiana tabacum modulated the sterol contents. The study could pave the way for understanding the metabolic flux regulation concerning biosynthesis of related sterols and triterpenoids. Supplementary Information The online version contains supplementary material available at 10.1007/s00709-021-01616-2.

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“…Phylogenetic analysis revealed that OsONS1 branches off from lupeol synthases, and is phylogenetically distant from the two L. clavatum α-onocerin synthases which branch off directly from sterol biosynthesis; thus, α-onocerin biosynthesis evolved convergently in these two plant species (Almeida et al, 2018). In addition, molecular docking simulation showed that OsONS1 alone produces α-onocerin in two cyclization steps, as opposed to the specialized LcLCC and LcLCD in Lycopods.…”

Section: Convergent Evolution In Biosynthesis Of Triterpenoid Scaffolmentioning

confidence: 95%

“…In O. spinosa a neofunctionalized squalene epoxidases (OsSQEs) provide the OSCs with the necessary bis-oxidosqualene. Fluorescence imaging microscopy experiments demonstrated protein-protein interactions between OsONS1 and the neofunctionalized OsSQEs (Almeida et al, 2018).…”

Section: Convergent Evolution In Biosynthesis Of Triterpenoid Scaffolmentioning

confidence: 99%

“…Subsequently α-onocerin synthase (LcLCD) carries out the cyclization of the D and E rings from the remaining epoxide ring, to yield α-onocerin. Our group demonstrated that Ononis spinosa α-onocerin is biosynthesized by a single OSC (OsONS1) (Almeida et al, 2018). In O. spinosa a neofunctionalized squalene epoxidases (OsSQEs) provide the OSCs with the necessary bis-oxidosqualene.…”

Section: Convergent Evolution In Biosynthesis Of Triterpenoid Scaffolmentioning

confidence: 99%

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Evolution of Structural Diversity of Triterpenoids

2019

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Plants have evolved to produce a blend of specialized metabolites that serve functional roles in plant adaptation. Among them, triterpenoids are one of the largest subclasses of such specialized metabolites, with more than 14,000 known structures. They play a role in plant defense and development and have potential applications within food and pharma. Triterpenoids are cyclized from oxidized squalene precursors by oxidosqualene cyclases, creating more than 100 different cyclical triterpene scaffolds. This limited number of scaffolds is the first step towards creating the vast structural diversity of triterpenoids followed by extensive diversification, in particular, by oxygenation and glycosylation. Gene duplication, divergence, and selection are major forces that drive triterpenoid structural diversification. The triterpenoid biosynthetic genes can be organized in non-homologous gene clusters, such as in Avena spp., Cucurbitaceae and Solanum spp., or scattered along plant chromosomes as in Barbarea vulgaris. Paralogous genes organized as tandem repeats reflect the extended gene duplication activities in the evolutionary history of the triterpenoid saponin pathways, as seen in B. vulgaris. We review and discuss examples of convergent and divergent evolution in triterpenoid biosynthesis, and the apparent mechanisms occurring in plants that drive their increasing structural diversity within and across species. Using B. vulgaris' saponins as examples, we discuss the impact a single structural modification can have on the structure of a triterpenoid and how this affect its biological properties. These examples provide insight into how plants continuously evolve their specialized metabolome, opening the way to study uncharacterized triterpenoid biosynthetic pathways.

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A Single Oxidosqualene Cyclase Produces the Seco-Triterpenoid α-Onocerin

Cited by 20 publications

References 56 publications

Tuscan Varieties of Sweet Cherry Are Rich Sources of Ursolic and Oleanolic Acid: Protein Modeling Coupled to Targeted Gene Expression and Metabolite Analyses

Tuscan Varieties of Sweet Cherry Are Rich Sources of Ursolic and Oleanolic Acid: Protein Modeling Coupled to Targeted Gene Expression and Metabolite Analyses

Transcriptome-wide identification of squalene epoxidase genes from Glycyrrhiza glabra L.: expression analysis and heterologous expression of GgSQE1 suggest important role in terpenoid biosynthesis

Evolution of Structural Diversity of Triterpenoids

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