Biology subjects

Grosjean, J.

Publications and source records attributed to Grosjean, J..

6 recordsLinked to original sources

bioRxiv2026

First O-demethylation activity in Arabidopsis specialized metabolism resolves the missing step in esculetin biosynthesis

Coumarins are phenylpropanoid-derived specialized metabolites that contribute to plant defence, shape plant-microbe interactions in the rhizosphere, and promote iron acquisition. In Arabidopsis thaliana, a model plant for iron-responsive coumarin metabolism, the enzymatic origin of the catecholic coumarin esculetin has long remained unresolved. Here we identify the first O-demethylation reaction in Arabidopsis specialized metabolism and show that 2-oxoglutarate- and Fe(II)-dependent dioxygenases catalyze scopoletin 6-O-demethylation to form esculetin. We designate these enzymes scopoletin 6-O-demethylases (S6ODs) and validate their activity through biochemical characterization, together with metabolomic profiling and independent loss-of-function mutant lines providing genetic evidence in planta. Disruption of S6OD activity remodels coumarin profiles and alters plant performance under limited iron availability, indicating that esculetin biosynthesis contributes to plant responses under these conditions. Our findings resolve the long-sought missing step in esculetin biosynthesis. It establishes O-demethylation as a previously unrecognized reaction in Arabidopsis specialized metabolism and suggest that 2OGD-mediated O-demethylation is recurrently recruited during evolution of plant metabolism, with implications for metabolic engineering and improvement of iron acquisition traits in crops.

plant biology↗

bioRxiv2025

Genotype-Specific Root Morphology and Metabolic Traits Shape Bacterial Communities and Tolerance to Fusarium Root Rot in Wheat

Plant genotype plays a critical role in shaping root-associated microbial communities and in modulating plant tolerance to soilborne diseases such as Fusarium root rot (FRR). In this study, we investigated how four wheat (Triticum aestivum) varieties, whose tolerance to FRR differs, influence the composition and structure of bacterial communities in the rhizosphere and root endosphere. We evaluated root traits that may contribute to the genotype-specific assembly of bacterial communities across the four wheat genotypes. The variety Concret exhibited the highest FRR tolerance, whereas Pilier was the most susceptible. Analyses of root morphology revealed significant genotype-dependent differences in root length and volume, which were positively correlated with the abundance of some rhizosphere bacteria affiliated with Bacillus, Lysobacter, and Sphingomonas. Untargeted metabolomics identified 879 features, with 20 key metabolites distinguishing the wheat genotypes, including alkaloids and benzoate- and benzoxazinoid-derived compounds. Correlation analysis revealed significant relationships between these root metabolites and key bacterial taxa. Our findings demonstrate that wheat genotypes influence the assembly of the root microbiota through genotype-based morphological and metabolic traits, providing valuable insights into traits that modulate the plant microbiome to improve wheat resistance to FRR.

ecology↗

bioRxiv2025

Introducing furanocoumarin biosynthetic genes in tomato results in coumarins accumulation and impacted growth

Over the past three decades, eeorts to decipher plant metabolism have shed light on key enzymes driving specialized metabolite biosynthesis. Although only few pathways have been completely investigated to date, their characterization paves the way for exploring the potential eeects of specialized metabolites on plant physiology. Among them is the linear furanocoumarin pathway, which was recently completed to produce up to psoralen. In this study, we report the first metabolic engineering of the linear furanocoumarin pathway to enable artificial psoralen production in tomato, through the integration of four genes coding for the enzymes: Umbelliferone Synthase, Demethylsuberosin Synthase, Marmesin Synthase and Psoralen Synthase. Interestingly, coumarins were produced instead of furanocoumarins. Using morphophysiological, metabolomic, and transcriptomic analyses, we suggest how coumarins, particularly scopoletin, can impact growth and aeect plant physiology, even at low concentrations. As coumarins have increasingly attracted interest for agricultural applications due to their minimal environmental impact, this work both expands and challenges their potential by highlighting the physiological costs and benefits they may impose on tomato. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=164 SRC="FIGDIR/small/663522v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1df0bdeorg.highwire.dtl.DTLVardef@843d9borg.highwire.dtl.DTLVardef@1e898b6org.highwire.dtl.DTLVardef@18205eb_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

plant biology↗

bioRxiv2024

Fingerprinting and chemotyping approaches reveal a wide genetic and metabolic diversity among wild hops (Humulus lupulus L.)

Hop (Humulus lupulus L.) is an emblematic industrial crop in the French North East region that developed at the same time as the brewing activity. Presently, this sector, especially microbreweries, are interested in endemic wild hops, which give beer production a local signature. In this study, we investigated the genetic and metabolic diversity of thirty-six wild hops sampled in various ecological environments. These wild accessions were propagated aeroponically and cultivated under uniform conditions (the same soil and the same environmental factors). Our phytochemical approach based on UHPLC-ESI-MS/MS analysis led to the identification of three metabolic clusters based on leaf content and characterized by variations in the contents of twelve specialized metabolites that were identified (including xanthohumol, bitter acids, and their oxidized derivatives). Furthermore, molecular characterization was carried out using sixteen EST-SSR microsatellites, allowing a genetic affiliation of our wild hops with hop varieties cultivated worldwide and wild hops genotyped to date using this method. Genetic proximity was observed for both European wild and hop varieties, especially for Strisselspalt, the historical variety of our region. Finally, our findings collectively assessed the impact of the hop genotype on the chemical phenotype through multivariate regression tree (MRT) analysis. Our results highlighted the WRKY 224 allele as a key discriminator between high- and low-metabolite producers. Moreover, the model based on genetic information explained 40% of the variance in the metabolic data. However, despite this strong association, the model lacked predictive power, suggesting that its applicability may be confined to the datasets analyzed.

plant biology↗

bioRxiv2020

Patient-derived xenografts and organoids model therapy response in prostate cancer

Therapy resistance and metastatic processes in prostate cancer (PCa) remain undefined, due to lack of experimental models that mimic different disease stages. We describe a novel androgen-dependent PCa patient-derived xenograft (PDX) model from treatment-naive, soft tissue metastasis (PNPCa). RNA and whole-exome sequencing of the PDX tissue and organoids confirmed transcriptomic and genomic similarity to primary tumor. PNPCa harbours BRCA2 and CHD1 somatic mutations, shows an SPOP/FOXA1-like transcriptomic signature and microsatellite instability, which occurs in 3% of advanced PCa and has never been modelled in vivo. Comparison of the treatment-naive PNPCa with additional metastatic PDXs (BM18, LAPC9), in a medium-throughput organoid screen of FDA-approved compounds, revealed differential drug sensitivities. Multikinase inhibitors (ponatinib, sunitinib, sorafenib) were broadly effective on all PDX- and patient-derived organoids from advanced cases with acquired resistance to standard-of-care compounds. This proof-of-principle study may provide a preclinical tool to screen drug responses to standard-of-care and newly identified, repurposed compounds.

cancer biology↗

bioRxiv2017

Scopoletin 8-hydroxylase: a novel enzyme involved in coumarin biosynthesis and iron-deficiency responses in Arabidopsis

HighlightA strongly iron-responsive gene of previously unknown function, At3g12900, encodes a scopoletin 8-hydroxylase involved in coumarin biosynthesis and plays an important role in the iron uptake strategy in Arabidopsis.\n\nAbstractIron (Fe) deficiency represents a serious agricultural problem, particularly in alkaline soils. Secretion of coumarins by Arabidopsis thaliana roots is induced under Fe-deficiency. An essential enzyme for the biosynthesis of major Arabidopsis coumarins, scopoletin and its derivatives, is Feruloyl-CoA 6-Hydroxylase1 (F6'H1) that belongs to a large enzyme family of the 2-oxoglutarate and Fe(II)-dependent dioxygenases. Another member of this family that is a close homologue of F6H1 and is encoded by a strongly Fe-responsive gene, At3g12900, is functionally characterized in the presented work. We purified the At3g12900 protein heterologously expressed in Escherichia coli and demonstrated that it is involved in the conversion of scopoletin into fraxetin via hydroxylation at the C8-position. Consequently, it was named scopoletin 8-hydroxylase (S8H). Its function in plant cells was confirmed by the transient expression of S8H protein in Nicotiana benthamiana leaves followed by the metabolite profiling and the biochemical and ionomic characterization of Arabidopsis s8h knockout lines grown under various regimes of Fe availability. Our results indicate that S8H is involved in coumarin biosynthesis as part of the Fe acquisition machinery.

plant biology↗