Biology subjects

Gaquerel, E.

Publications and source records attributed to Gaquerel, E..

9 recordsLinked to original sources

bioRxiv2026

Discovery of Scrophularia nodosa harpagoside synthase, a novel BAHD cinnamoyltransferase, bridges a key gap in the iridoid biosynthetic pathway

Harpagoside, a high-value anti-inflammatory iridoid compound, is traditionally extracted from the roots of Harpagophytum procumbens (Pedaliaceae, Lamiales), a Southern African desert plant widely used in traditional medicine but currently threatened by overexploitation. Scrophularia nodosa (Scrophulariaceae, Lamiales) is a perennial annual plant widely distributed in Western Europe and accumulates several iridoid compounds with known biological activities, such as catalpol, aucubin, harpagide and particularly harpagoside. We gathered extensive genomic and transcriptomics resources for this species and aimed at deciphering the biosynthetic pathway leading to the most abundant iridoid in S. nodosa, harpagoside. We found that the early iridoid pathway is well conserved with other iridoid-producing plants and validated the enzyme activities by transient co-expression in N. benthamiana. Investigation into the large BAHD family showed subclade 6i expanding in Scrophulariaceae, with an atypical VYPWG motif instead of the canonical DFGWG. In this branch, we discovered and characterized harpagoside synthase, a BAHD-type cinnamoyl transferase enzyme showing unique high specificity to the uncommon cinnamoyl-CoA acyl donor and catalyzing the final step of harpagoside biosynthesis. These results establish S. nodosa as a new model to investigate unexplored branches of the iridoids metabolism, and are a first step towards sustainable harpagoside and high-value cinnamoyl-containing conjugates production.

plant biology↗

bioRxiv2023

Mass2SMILES: deep learning based fast prediction of structures and functional groups directly from high-resolution MS/MS spectra.

Modern mass spectrometry-based metabolomics generates vast amounts of mass spectral data as part of the chemical inventory of biospecimens. Annotation of the resulting MS/MS spectra remains a challenging task that mostly relies on database interrogations, in silico prediction and interpretation of diagnostic fragmentation schemes and/or expert knowledge-based manual interpretations. A key limitation is additionally that these approaches typically leave a vast proportion of the (bio)chemical space unannotated. Here we report a deep neural network method to predict chemical structures solely from high-resolution MS/MS spectra. This novel approach initially relies on the encoding of SMILES strings from chemical structures using a continuous chemical descriptor space that had been previously implemented for molecule design. The deep neural network was trained on 83,358 natural product-derived MS/MS spectra of the GNPS library and of the NIST HRMS database with addition of the calculated neutral losses for those spectra. After this training and parameter optimization phase, the deep neural network approach was then used to predict structures from MS/MS spectra not included in the training data-set. Our current version, implemented in the Python programming language, accurately predicted 7 structures from 744 validation structures and the following 14 structures had a Tanimoto similarity score above 0.9 when compared to the true structure. It was also able to correctly identify two structures from the CASMI 2022 international contest. On average the Tanimoto similarity is of 0.40 for data of the CASMI 2022 international contest and of 0.39 for the validation data-set. Finally, our deep neural network is also able to predict the number of 60 functional groups as well as the molecular formula of chemical structures and adduct type for the analyzed MS/MS spectra. Importantly, this deep neural network approach is extremely fast, in comparison to currently available methods, making it suitable to predict on regular computers structures for all substances within large metabolomics datasets.

bioinformatics↗

bioRxiv2022

Evolutionary metabolomics of specialized metabolism diversification in the genus Nicotiana highlights allopolyploidy-mediated innovations in N-acylnornicotine metabolism

Specialized metabolite (SM) diversification is a core process to plants adaptation to diverse ecological niches. Here we implemented a computational mass spectrometry (MS)-based metabolomics approach to explore SM diversification in tissues of 20 species covering Nicotiana phylogenetics sections. To drastically increase metabolite annotation, we created a large in silico fragmentation database, comprising more than 1 million structures, and scripts for connecting class prediction to consensus substructures. Altogether, the approach provides an unprecedented cartography of SM diversity and section-specific innovations in this genus. As a case-study, and in combination with NMR and MS imaging, we explored the distribution of N-acyl nornicotines, alkaloids predicted to be specific to Repandae allopolyploids, and revealed their prevalence in the genus, albeit at much lower magnitude, as well as a greater structural diversity than previously thought. Altogether, the novel data integration approaches provided here should act as a resource for future research in plant SM evolution. TeaserComputational metabolomics delineates main trends in the diversification of specialized metabolism in the genus Nicotiana

plant biology↗

bioRxiv2022

TOR acts as metabolic gatekeeper for auxin-dependent lateral root initiation in Arabidopsis thaliana

Plants post-embryonic organogenesis requires matching the available metabolic resources to the developmental programs. The root system is determined by the formation of lateral roots (LR), which in Arabidopsis thaliana entails the auxin-induced activation of founder cells located in the pericycle. While the allocation of sugars to roots influences root branching, how sugar availability is sensed for auxin-triggered formation of LRs remains unknown. Here, we combine metabolic profiling with cell-specific genetic interference to show that LR formation is an important sink for carbohydrate accompanied by a switch to glycolysis. We show that the target-of-rapamycin (TOR) kinase is locally activated in the pericycle and the founder cells and that both chemical and genetic inhibition of TOR kinase lead to a block of LR initiation. TOR marginally affects the auxin-induced transcriptional response of the pericycle but modulates the translation of ARF19, ARF7 and LBD16, three key targets of auxin signalling. These data place TOR as a gatekeeper for post-embryonic LR formation that integrates local auxin-dependent pathways with systemic metabolic signals, modulating the translation of auxin induced gene expression.

plant biology↗

bioRxiv2021

Evolutionary footprints of a cold relic in a rapidly warming world

With accelerating global warming, understanding the evolutionary dynamics of plant adaptation to environmental change is increasingly urgent. Here we reveal the enigmatic history of the genus Cochlearia (Brassicaceae), a Pleistocene relic that originated from a drought-adapted Mediterranean sister genus during the Miocene. Cochlearia rapidly diversified and adapted to circum-Arctic regions and other cold-characterized habitat types during the Pleistocene. This rapid change in ecological preferences was accompanied by a highly complex, reticulate polyploid evolution, which was apparently triggered by the impact of repeated Pleistocene glaciation cycles. Our results illustrate that two early diversified arctic-alpine diploid gene pools contributed differently to the evolution of this young polyploid genus now captured in a cold-adapted niche. Metabolomics revealed ancestral central carbon metabolism responses to cold in diverse ecotypes, likely due to continuous connections to cold habitats that we hypothesize facilitated widespread parallel adaptation to alpine and subalpine habitats, and which we speculate were coopted from existing drought adaptations. Given the growing scientific interest in adaptive evolution of temperature-related traits, our results provide much-needed taxonomic and phylogenomic resolution of a model system as well as first insights into the origins of its adaptation to cold.

evolutionary biology↗

bioRxiv2020

Specific decorations of 17-hydroxygeranyllinalool diterpene glycosides solve the autotoxicity problem of chemical defense in Nicotiana attenuata

17-hydroxygeranyllinalool diterpene glycosides (HGL-DTGs) are abundant and potent anti-herbivore defense metabolites in Nicotiana attenuata whose glycosylation and malonylation biosynthetic steps are regulated by jasmonate signaling. To characterize the biosynthetic pathway of HGL-DTGs, we conducted a genome-wide analysis of uridine diphosphate glycosyltransferases (UGTs) and identified 107 members of family-1 UGTs. Tissue-specific time-course transcriptional profiling revealed that the transcripts of three UGTs were highly correlated with two HGL-DTG key biosynthetic genes: geranylgeranyl diphosphate synthase (NaGGPPS) and geranyllinalool synthase (NaGLS). NaGLSs role in HGL-DTG biosynthesis was confirmed by virus-induced gene-silencing. Silencing the UDP-rhamnosyltransferase, UGT91T1, indicated its role in the rhamnosylation of HGL-DTGs. In vitro enzyme assays revealed that UGT74P3 and UGT74P4 use UDP-glucose for the glucosylation of 17-hydroxygeranyllinalool (17-HGL) to lyciumoside I. UGT74P3 and UGT74P5 stably silenced plants were severely developmentally deformed, suggesting a phytotoxic effect of 17-HGL. Applications of synthetic 17-HGL and silencing of these UGTs in HGL-DTG-free plants confirmed the phytotoxic effect of 17-HGL. Feeding assays with Manduca sexta larvae revealed the defensive functions of the glucosylation and rhamnosylation steps in HGL-DTG biosynthesis. Glucosylation is a critical step that contributes to the metabolites defensive function and solves the autotoxicity problem of this potent chemical defense.

plant biology↗

bioRxiv2020

Ethylene is a local modulator of jasmonate-dependent phenolamide accumulation during Manduca sexta herbivory in Nicotiana attenuata

AO_SCPLOWBSTRACTC_SCPLOWRapid reconfigurations of intimately connected phytohormone signaling networks allow plants to tune their physiology to constantly varying ecological conditions. During insect herbivory, most of the induced changes in defense-related leaf specialized metabolites are controlled by jasmonate (JA) signaling, which, in the wild tobacco Nicotiana attenuata, recruits MYB8, a transcription factor controlling the accumulation of phenolic-polyamine conjugates (phenolamides). In this and other plant species, herbivory also locally triggers ethylene (ET) production but the outcome of the JA-ET crosstalk at the level of secondary metabolism regulation has remained superficially investigated. Here, we analyzed local and systemic herbivory-induced changes by mass spectrometry-based metabolomics in leaves of transgenic plants impaired in JA, ET and MYB8 signaling. Parsing deregulations in this factorial data-set identified a network of JA/MYB8-dependent phenolamides for which impairment of ET signaling attenuated their accumulation only in locally-damaged leaves. Further experiments revealed that ET, albeit biochemically interrelated to polyamine metabolism via the intermediate S-adenosylmethionine, does not impart on free polyamine levels, but instead significantly modulates phenolamide levels and marginally affected transcript levels in this pathway. This study identifies ET as a local modulator of phenolamide investments and provides a metabolomics data-platform to mine associations between herbivory-induced signaling and specialized metabolite groups in N. attenuata. SO_SCPLOWUMMARYC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWSTATEMENTC_SCPLOWHerbivory-elicited ethylene acts as a local enhancer of the production of jasmonate/MYB8-dependent phenolamides during the defense response of Nicotiana attenuata leaves against herbivory by the lepidopteran larva Manduca sexta.

plant biology↗

bioRxiv2020

Information theory tests critical predictions of plant defense theory for specialized metabolism

Different plant defense theories have provided important theoretical guidance in explaining patterns in plant specialized metabolism, but their critical predictions remain to be tested. Here, we systematically explored the metabolomes of Nicotiana attenuata, from single plants to populations, as well as of closely-related species, using unbiased MS/MS analyses and processed the abundances of compound-spectrum-based MS features within an information theory framework to test critical predictions of Optimal Defense (OD) and Moving Target (MT) theories. Information components of herbivory-elicited plant metabolomes were fully consistent with the OD theory predictions and contradicted the main prediction of the MT theory. From micro- to macro-evolutionary scales, jasmonate signaling was identified as the master determinant of OD while ethylene signaling provided fine-tuning for herbivore-specific responses annotated via MS/MS molecular networks. One-sentence summaryInformation theory tests defense theory predictions by providing a common currency for comparison of specialized metabolomes

plant biology↗

bioRxiv2017

Wild tobacco genomes reveal the evolution of nicotine biosynthesis

Nicotine, the signature alkaloid of Nicotiana species responsible for the addictive properties of human tobacco smoking, functions as a defensive neurotoxin against attacking herbivores. However, the evolution of the genetic features that contributed to the assembly of the nicotine biosynthetic pathway remains unknown. We sequenced and assembled genomes of two wild tobaccos, Nicotiana attenuata (2.5 Gb) and N. obtusifolia (1.5 Gb), two ecological models for investigating adaptive traits in nature. We show that after the Solanaceae whole genome triplication event, a repertoire of rapidly expanding transposable elements (TEs) bloated these Nicotiana genomes, promoted expression divergences among duplicated genes and contributed to the evolution of herbivory-induced signaling and defenses, including nicotine biosynthesis. The biosynthetic machinery that allows for nicotine synthesis in the roots evolved from the stepwise duplications of two ancient primary metabolic pathways: the polyamine and nicotinic acid dinucleotide (NAD) pathways. While the duplication of the former is shared among several Solanaceous genera which produce polyamine-derived tropane alkaloids, the innovation and efficient production of nicotine in the genus Nicotiana required lineage-specific duplications within the NAD pathway and the evolution of root-specific expression of the duplicated Solanaceae-specific ethylene response factor (ERF) that activates the expression of all nicotine biosynthetic genes. Furthermore, TE insertions that incorporated transcription factor binding motifs also likely contributed to the coordinated metabolic flux of the nicotine biosynthetic pathway. Together, these results provide evidence that TEs and gene duplications facilitated the emergence of a key metabolic innovation relevant to plant fitness.

genomics↗