197 results on '"Courdavault, V."'
Search Results
2. Highlighting type A RRs as potential regulators of the dkHK1 multi-step phosphorelay pathway in Populus
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Chefdor, F., Héricourt, F., Koudounas, K., Carqueijeiro, I., Courdavault, V., Mascagni, F., Bertheau, L., Larcher, M., Depierreux, C., Lamblin, F., Racchi, M.L., and Carpin, S.
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- 2018
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3. Les levures du clade CTG (clade Candida) : biologie, incidence en santé humaine et applications en biotechnologie
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Defosse, T.A., Le Govic, Y., Courdavault, V., Clastre, M., Vandeputte, P., Chabasse, D., Bouchara, J.-P., Giglioli-Guivarc’h, N., and Papon, N.
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- 2018
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4. Biosynthesis and Regulation of Alkaloids
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Guirimand, G., Courdavault, V., St-Pierre, B., Burlat, V., Pua, Eng Chong, editor, and Davey, Michael R., editor
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- 2010
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5. Prequels to Synthetic Biology
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Foureau, E., primary, Carqueijeiro, I., additional, Dugé de Bernonville, T., additional, Melin, C., additional, Lafontaine, F., additional, Besseau, S., additional, Lanoue, A., additional, Papon, N., additional, Oudin, A., additional, Glévarec, G., additional, Clastre, M., additional, St-Pierre, B., additional, Giglioli-Guivarc’h, N., additional, and Courdavault, V., additional
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- 2016
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6. Chapter Eight - Prequels to Synthetic Biology: From Candidate Gene Identification and Validation to Enzyme Subcellular Localization in Plant and Yeast Cells
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Foureau, E., Carqueijeiro, I., Dugé de Bernonville, T., Melin, C., Lafontaine, F., Besseau, S., Lanoue, A., Papon, N., Oudin, A., Glévarec, G., Clastre, M., St-Pierre, B., Giglioli-Guivarc’h, N., and Courdavault, V.
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- 2016
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7. Folivory elicits a strong defense reaction in Catharanthus roseus: metabolomic and transcriptomic analyses reveal distinct local and systemic responses
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de Bernonville, T., Carqueijeiro, I., Lanoue, A., Lafontaine, F., Bel, P., Liesecke, F., Musset, K., Oudin, A., Glevarec, G., Pichon, O., Besseau, S., Clastre, M., St-Pierre, B., Flors, V., Maury, S., Huguet, E., O'Connor, S., Courdavault, V., Biomolécules et biotechnologies végétales (BBV EA 2106), Université de Tours, Dept CAMN, Plant Physiol Sect, Metab Integrat & Cell Signaling Grp, Universitat Jaume I, Institut de recherche sur la biologie de l'insecte UMR7261 (IRBI), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université Francois Rabelais [Tours], Laboratoire de Biologie des Ligneux et des Grandes Cultures (LBLGC), Institut National de la Recherche Agronomique (INRA)-Université d'Orléans (UO), Centre National de la Recherche Scientifique (CNRS), Department of Biological Chemistry, Weizmann Institute of Science, Université de Tours (UT), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Weizmann Institute of Science [Rehovot, Israël]
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Transcription, Genetic ,endocrine system diseases ,periwinkle (plant) ,approche transcriptomique ,Catharanthus ,monoterpène ,interaction plante insecte ,Cyclopentanes ,alcaloide indolique ,Models, Biological ,Article ,Indole Alkaloids ,catharanthus roseus ,manduca sexta ,Gene Expression Regulation, Plant ,Manduca ,Animals ,Metabolomics ,[SDV.BV]Life Sciences [q-bio]/Vegetal Biology ,Herbivory ,Oxylipins ,RNA, Messenger ,Photosynthesis ,Plant Proteins ,secondary metabolism ,Vegetal Biology ,Gene Expression Profiling ,fungi ,métabolisme secondaire ,plant insect interaction ,Biosynthetic Pathways ,Plant Leaves ,Larva ,Monoterpenes ,Secondary metabolism ,Plant sciences ,Biologie végétale - Abstract
Plants deploy distinct secondary metabolisms to cope with environment pressure and to face bio-aggressors notably through the production of biologically active alkaloids. This metabolism-type is particularly elaborated in Catharanthus roseus that synthesizes more than a hundred different monoterpene indole alkaloids (MIAs). While the characterization of their biosynthetic pathway now reaches completion, still little is known about the role of MIAs during biotic attacks. As a consequence, we developed a new plant/herbivore interaction system by challenging C. roseus leaves with Manduca sexta larvae. Transcriptomic and metabolic analyses demonstrated that C. roseus respond to folivory by both local and systemic processes relying on the activation of specific gene sets and biosynthesis of distinct MIAs following jasmonate production. While a huge local accumulation of strictosidine was monitored in attacked leaves that could repel caterpillars through its protein reticulation properties, newly developed leaves displayed an increased biosynthesis of the toxic strictosidine-derived MIAs, vindoline and catharanthine, produced by up-regulation of MIA biosynthetic genes. In this context, leaf consumption resulted in a rapid death of caterpillars that could be linked to the MIA dimerization observed in intestinal tracts. Furthermore, this study also highlights the overall transcriptomic control of the plant defense processes occurring during herbivory. We gratefully acknowledge the financial support from the “Région Centre” (France, ABISAL grant) and from the University of Tours.
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- 2017
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8. Prequels to Synthetic Biology: From Candidate Gene Identification and Validation to Enzyme Subcellular Localization in Plant and Yeast Cells
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Foureau, E., Carqueijeiro, I., Dugé de Bernonville, T., Melin, C., Lafontaine, F., Besseau, S., Lanoue, A., Papon, N., Oudin, A., Glevarec, G., Clastre, M., St-Pierre, B., Giglioli-Guivarc’h, N., Courdavault, V., Biomolécules et biotechnologies végétales (BBV EA 2106), Université de Tours (UT), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), and Université de Tours
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[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,[SDV.BV]Life Sciences [q-bio]/Vegetal Biology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2016
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9. HETEROYOHIMBINE SYNTHASE HYS FROM CATHARANTHUS ROSEUS - APO FORM
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Stavrinides, A., primary, Tatsis, E.C., additional, Caputi, L., additional, Foureau, E., additional, Stevenson, C.E.M., additional, Lawson, D.M., additional, Courdavault, V., additional, and O'Connor, S.E., additional
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- 2016
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10. HETEROYOHIMBINE SYNTHASE THAS1 FROM CATHARANTHUS ROSEUS - COMPLEX WITH NADP+
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Stavrinides, A., primary, Tatsis, E.C., additional, Caputi, L., additional, Foureau, E., additional, Stevenson, C.E.M., additional, Lawson, D.M., additional, Courdavault, V., additional, and O'Connor, S.E., additional
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- 2016
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11. HETEROYOHIMBINE SYNTHASE THAS1 FROM CATHARANTHUS ROSEUS - APO FORM
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Stavrinides, A., primary, Tatsis, E.C., additional, Caputi, L., additional, Foureau, E., additional, Stevenson, C.E.M., additional, Lawson, D.M., additional, Courdavault, V., additional, and O'Connor, S.E., additional
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- 2016
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12. In planta validation of HK1 homodimerization and recruitment of preferential HPt downstream partners involved in poplar multistep phosphorelay systems
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Bertheau, L, Miranda, M, Foureau, E, Rojas Hoyos LF, Chefdor, F, Héricourt, F, Depierreux, C, Morabito, D, Papon, N, Clastre, M, Scippa, Gabriella, Brignolas, F, Courdavault, V, and Carpin, S
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- 2013
13. Deciphering the Evolution, Cell Biology and Regulation of Monoterpene Indole Alkaloids
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Lanoue, Arnaud, Oudin, Audrey, St-Pierre, Benoit, Dutilleul, C., martine, courtois, Glevarec, Gaëlle, Crèche, J., Clastre, M., Giglioli-Guivarc'H, N., Papon, N., Besseau, S., Courdavault, V., Eric, Ducos, Dugé De Bernonville, Thomas, nadine, imbault, olivier, pichon, Biomolécules et biotechnologies végétales (BBV EA 2106), Université de Tours, INH : Pathologie végétale : biodiversité, écologie, interactions bioagresseurs-plantes (PAVE), Institut National de la Recherche Agronomique (INRA)-Université d'Angers (UA), and Financial support was provided by the ‘Ministère de l’Enseignement Supérieur et de la Recherche’ (MESR, France), the University of Tours, the ‘Région Centre', and the ‘Ligue Contre le Cancer, comite´ d’Indre et Loire’.
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[SDV.BV]Life Sciences [q-bio]/Vegetal Biology - Abstract
International audience; Monoterpene indole alkaloids (MIAs) constitute a large group of specialised metabolites with many potent pharmaceutical properties, including the antitumoral vinblastine and hypotensive ajmalicine. Hence a large body of phytochemical investigation delineates the distribution and diversity of various MIA structural classes in Gentianales families. The biosynthetic pathway of these secondary metabolites involves several specific branches, including indole and monoterpenoid formations, secoiridoid assembly, central MIA biosynthesis and branch-specific reactions, as well as supply of primary metabolite precursors by the methylerythritol phosphate and shikimate pathways. Several genes and enzymatic activities involved in these pathways have been characterised, allowing detailed analysis of the molecular biology of this system in model plants such as Catharanthus roseus and Rauvolfia serpentina. With the prospects of improving production of MIAs in plant and cell culture, regulations of biosynthetic capacities have been thoroughly investigated. This pathway also presents a high degree of spatial organisation at the organ, cellular and subcellular levels. This chapter presents an overview of the structural diversity, the complexity of MIA biosynthesis, and regulation with an evolutionary perspective.
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- 2013
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14. Virus-induced gene silencing inCatharanthus roseusby biolistic inoculation of tobacco rattle virus vectors
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Carqueijeiro, I., primary, Masini, E., additional, Foureau, E., additional, Sepúlveda, L. J., additional, Marais, E., additional, Lanoue, A., additional, Besseau, S., additional, Papon, N., additional, Clastre, M., additional, Dugé de Bernonville, T., additional, Glévarec, G., additional, Atehortùa, L., additional, Oudin, A., additional, and Courdavault, V., additional
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- 2015
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15. In plantavalidation of HK1 homodimerization and recruitment of preferential HPt downstream partners involved in poplar multistep phosphorelay systems
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Bertheau, L., primary, Miranda, M., additional, Foureau, E., additional, Rojas Hoyos, L.F., additional, Chefdor, F., additional, Héricourt, F., additional, Depierreux, C., additional, Morabito, D., additional, Papon, N., additional, Clastre, M., additional, Scippa, G.S., additional, Brignolas, F., additional, Courdavault, V., additional, and Carpin, S., additional
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- 2013
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16. Molecular cloning and characterisation of two calmodulin isoforms of the Madagascar periwinkle Catharanthus roseus
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Poutrain, P., primary, Guirimand, G., additional, Mahroug, S., additional, Burlat, V., additional, Melin, C., additional, Ginis, O., additional, Oudin, A., additional, Giglioli‐Guivarc’h, N., additional, Pichon, O., additional, and Courdavault, V., additional
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- 2010
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17. Virus-induced gene silencing in Catharanthus roseus by biolistic inoculation of tobacco rattle virus vectors.
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Carqueijeiro, I., Masini, E., Foureau, E., Sepúlveda, L. J., Marais, E., Lanoue, A., Besseau, S., Papon, N., Clastre, M., Dugé de Bernonville, T., Glévarec, G., Atehortùa, L., Oudin, A., Courdavault, V., and Luo, Z. B.
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PLANT gene silencing ,CATHARANTHUS roseus ,TOBACCO rattle virus ,PLANT inoculation ,MONOTERPENOIDS ,INDOLE alkaloids - Abstract
Catharanthus roseus constitutes the unique source of several valuable monoterpenoid indole alkaloids, including the antineoplastics vinblastine and vincristine. These alkaloids result from a complex biosynthetic pathway encompassing between 30 and 50 enzymatic steps whose characterisation is still underway. The most recent identifications of genes from this pathway relied on a tobacco rattle virus-based virus-induced gene silencing ( VIGS) approach, involving an Agrobacterium-mediated inoculation of plasmids encoding the two genomic components of the virus. As an alternative, we developed a biolistic-mediated approach of inoculation of virus-encoding plasmids that can be easily performed by a simple bombardment of young C. roseus plants. After optimisation of the transformation conditions, we showed that this approach efficiently silenced the phytoene desaturase gene, leading to strong and reproducible photobleaching of leaves. This biolistic transformation was also used to silence a previously characterised gene from the alkaloid biosynthetic pathway, encoding iridoid oxidase. Plant bombardment caused down-regulation of the targeted gene (70%), accompanied by a correlated decreased in MIA biosynthesis (45-90%), similar to results obtained via agro-transformation. Thus, the biolistic-based VIGS approach developed for C. roseus appears suitable for gene function elucidation and can readily be used instead of the Agrobacterium-based approach, e.g. when difficulties arise with agro-inoculations or when Agrobacterium-free procedures are required to avoid plant defence responses. [ABSTRACT FROM AUTHOR]
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- 2015
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18. In planta validation of HK1 homodimerization and recruitment of preferential HPt downstream partners involved in poplar multistep phosphorelay systems.
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Bertheau, L., Miranda, M., Foureau, E., Rojas Hoyos, L.F., Chefdor, F., Héricourt, F., Depierreux, C., Morabito, D., Papon, N., Clastre, M., Scippa, G.S., Brignolas, F., Courdavault, V., and Carpin, S.
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DIMERIZATION ,HISTIDINE kinases ,PHOSPHOTRANSFERASES ,POPLARS ,ARABIDOPSIS ,PLANT proteins ,PLANT cytoplasm - Abstract
Multistep phosphorelays involve a phosphate transfer from sensor histidine-aspartate kinases (HKs) to response regulators (RRs), via histidine-containing phosphotransfer proteins (HPts). InArabidopsis, some AHK receptors are organized as homodimers and able to interact with HPts (AHPs). However, there are no data available concerning the dimerization of theArabidopsisosmosensor AHK1. Although only AHP2 is able to interact with AHK1 in yeast, validation of this interaction remains to be clarified in planta. The ability of poplar HK1 osmosensor, homologous to AHK1, to homodimerize and interact with three HPts (HPt2, 7 and 9) as preferential partners has been previously shown by yeast two-hybrid assay. However, protein interaction studies need to use complementary approaches to avoid interaction artifacts. Here, we confirmedin plantahomodimerization of the cytoplasmic part of HK1 (HK1-CP) and the functional relevance of HK1-CP/HPt interactions by bimolecular fluorescence complementation assays. This work led us to validate these partnerships and to propose them as probably involved in osmosensing pathway inPopulus. [ABSTRACT FROM PUBLISHER]
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- 2013
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19. Molecular cloning and characterisation of two calmodulin isoforms of the Madagascar periwinkle Catharanthus roseus.
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Poutrain, P., Guirimand, G., Mahroug, S., Burlat, V., Melin, C., Ginis, O., Oudin, A., Giglioli-Guivarc'h, N., Pichon, O., and Courdavault, V.
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CATHARANTHUS roseus ,CALMODULIN ,MOLECULAR cloning ,MONOTERPENES ,RECOMBINANT proteins ,INDOLE alkaloid synthesis ,IN situ hybridization ,POLYMERASE chain reaction - Abstract
Involvement of Casignalling in regulation of the biosynthesis of monoterpene indole alkaloids (MIA) in Catharanthus roseus has been extensively studied in recent years, albeit no protein of this signalling pathway has been isolated. Using a PCR strategy, two C. roseus cDNAs encoding distinct calmodulin (CAM) isoforms were cloned and named CAM1 and CAM2. The deduced 149 amino acid sequences possess four Ca binding domains and exhibit a close identity with Arabidopsis CAM isoforms (>91%). The ability of CAM1 and CAM2 to bind Ca was demonstrated following expression of the corresponding recombinant proteins. Furthermore, transient expression of CAM1-GFP and CAM2-GFP in C. roseus cells showed a typical nucleo-cytoplasm localisation of both CAMs, in agreement with the wide distribution of CAM target proteins. Using RNA blot analysis, we showed that CAM1 and CAM2 genes had a broad pattern of expression in C. roseus organs and are constitutively expressed during a C. roseus cell culture cycle, with a slight inhibitory effect of auxin for CAM1. Using RNA in situ hybridisation, we also detected CAM1 and CAM2 mRNA in the vascular bundle region of young seedling cotyledons. Finally, using specific inhibitors, we also showed that CAMs are required for MIA biosynthesis in C. roseus cells by acting on regulation of expression of genes encoding enzymes that catalyse early steps of MIA biosynthesis, such as 1-deoxy--xylulose 5-phosphate reductoisomerase and geraniol 10-hydroxylase. [ABSTRACT FROM AUTHOR]
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- 2011
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20. An additional Meyerozyma guilliermondii IMH3 gene confers mycophenolic acid resistance in fungal CTG clade species
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Ta, Defosse, Melin C, Clastre M, Besseau S, Arnaud LANOUE, Glévarec G, Oudin A, Td, Bernonville, Vandeputte P, Linder T, Jp, Bouchara, Courdavault V, Giglioli-Guivarc'h N, and Papon N
21. Isolation of a cDNA encoding the alpha-subunit of CAAX-prenyltransferases from Catharanthus roseus and the expression of the active recombinant protein farnesyltransferase
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Courdavault V, Burlat V, Benoit St-Pierre, Gantet P, and Giglioli-Guivarc'h N
22. A GAME changer in steroidal metabolite biosynthesis.
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Lezin E, Papon N, and Courdavault V
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- 2025
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23. Editorial overview: Physiology and metabolism 2024.
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Courdavault V and Osbourn A
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- 2024
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24. Genome-based discovery of pachysiphine synthases in Tabernaemontana elegans.
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Lezin E, Durand M, Birer Williams C, Lopez Vazquez AL, Perrot T, Gautron N, Pétrignet J, Cuello C, Jansen HJ, Magot F, Szwarc S, Le Pogam P, Beniddir MA, Koudounas K, Oudin A, St-Pierre B, Giglioli-Guivarc'h N, Sun C, Papon N, Jensen MK, Dirks RP, O'Connor SE, Besseau S, and Courdavault V
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- Cytochrome P-450 Enzyme System genetics, Cytochrome P-450 Enzyme System metabolism, Plant Proteins genetics, Plant Proteins metabolism, Secologanin Tryptamine Alkaloids metabolism, Indole Alkaloids metabolism, Genome, Plant genetics, Tabernaemontana genetics, Tabernaemontana metabolism, Phylogeny
- Abstract
Plant-specialized metabolism represents an inexhaustible source of active molecules, some of which have been used in human health for decades. Among these, monoterpene indole alkaloids (MIAs) include a wide range of valuable compounds with anticancer, antihypertensive, or neuroactive properties. This is particularly the case for the pachysiphine derivatives which show interesting antitumor and anti-Alzheimer activities but accumulate at very low levels in several Tabernaemontana species. Unfortunately, genome data in Tabernaemontanaceae are lacking and knowledge on the biogenesis of pachysiphine-related MIAs in planta remains scarce, limiting the prospects for the biotechnological supply of many pachysiphine-derived biopharmaceuticals. Here, we report a raw version of the toad tree (Tabernaemontana elegans) genome sequence. These new genomic resources led to the identification and characterization of a couple of genes encoding cytochrome P450 with pachysiphine synthase activity. Our phylogenomic and docking analyses highlight the different evolutionary processes that have been recruited to epoxidize the pachysiphine precursor tabersonine at a specific position and in a dedicated orientation, thus enriching our understanding of the diversification and speciation of the MIA metabolism in plants. These gene discoveries also allowed us to engineer the synthesis of MIAs in yeast through the combinatorial association of metabolic enzymes resulting in the tailor-made synthesis of non-natural MIAs. Overall, this work represents a step forward for the future supply of pachysiphine-derived drugs by microbial cell factories., (© 2024 The Author(s). The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)
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- 2024
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25. Harnessing the spatial and transcriptional regulation of monoterpenoid indole alkaloid metabolism in Alstonia scholaris leads to the identification of broad geissoschizine cyclase activities.
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Méteignier LV, Szwarc S, Barunava P, Durand M, Zamar DL, Birer Williams C, Gautron N, Dutilleul C, Koudounas K, Lezin E, Perrot T, Oudin A, Pateyron S, Delannoy E, Brunaud V, Lanoue A, Abbasi BH, St-Pierre B, Jensen MK, Papon N, Sun C, Le Pogam P, Yuan L, Beniddir MA, Besseau S, and Courdavault V
- Abstract
Monoterpene indole alkaloids (MIAs) are valuable metabolites produced in numerous medicinal plants from the Apocynaceae family such as Alstonia scholaris, which synthesizes strictamine, a MIA displaying neuropharmacological properties of a potential importance. To get insights into the MIA metabolism in A. scholaris, we studied here both the spatial and transcriptional regulations of MIA genes by performing a robust transcriptomics analysis of the main plant organs, leaf epidermis but also by sequencing RNA from leaves transiently overexpressing the master transcriptional regulator MYC2. These transcriptomic studies notably demonstrated that the first steps of the MIA pathway are successively distributed in the internal phloem associated parenchyma and epidermis, and that MYC2 exerts a remarkable transcriptional effect by modulating the expression of around 1000 genes. By combining these distinct datasets, we initiated the search for MIA-related genes encoding CYP71, based on the similarity of expression compared to already known MIA genes. Transient expression of these candidates in Nicotiana benthamiana leaves and yeast notably led to the identification of a related isoform of rhazimal synthase (RHS) capable of converting the MIA precursor geissoschizine into akuammicine, strictamine and 16-epi-pleiocarpamine. Investigating its catalytic mechanism revealed that strictamine results from rhazimal deformylation and that a similar mechanism may also explain 16-epi-pleiocarpamine synthesis. This prompted us to rename these enzymes geissoschizine cyclase due to their capacity of cyclizing geissoschizine into three different MIA scaffolds and to form both C-C and C-N bonds. This identification thus illustrates the potential of integrating spatial and transcriptional regulation analysis for MIA gene identification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)
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- 2024
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26. Structure and distribution of sensor histidine kinases in the fungal kingdom.
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Mina S, Hérivaux A, Yaakoub H, Courdavault V, Wéry M, and Papon N
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- Genome, Fungal, Signal Transduction, Fungal Proteins genetics, Fungal Proteins metabolism, Fungal Proteins chemistry, Evolution, Molecular, Protein Kinases genetics, Protein Kinases metabolism, Protein Kinases chemistry, Histidine Kinase genetics, Histidine Kinase metabolism, Histidine Kinase chemistry, Phylogeny, Fungi genetics, Fungi enzymology, Fungi classification
- Abstract
Two-component systems (TCSs) are diverse cell signaling pathways that play a significant role in coping with a wide range of environmental cues in both prokaryotic and eukaryotic organisms. These transduction circuitries are primarily governed by histidine kinases (HKs), which act as sensing proteins of a broad variety of stressors. To date, nineteen HK groups have been previously described in the fungal kingdom. However, the structure and distribution of these prominent sensing proteins were hitherto investigated in a limited number of fungal species. In this study, we took advantage of recent genomic resources in fungi to refine the fungal HK classification by deciphering the structural diversity and phylogenetic distribution of HKs across a large number of fungal clades. To this end, we browsed the genome of 91 species representative of different fungal clades, which yielded 726 predicted HK sequences. A domain organization analysis, coupled with a robust phylogenomic approach, led to an improved categorization of fungal HKs. While most of the compiled sequences were categorized into previously described fungal HK groups, some new groups were also defined. Overall, this study provides an improved overview of the structure, distribution, and evolution of HKs in the fungal kingdom., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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27. Plant drugs: Transcending the mescaline biosynthesis.
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Courdavault V and Papon N
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- Cactaceae metabolism, Hallucinogens metabolism, Mescaline metabolism
- Abstract
Our knowledge of the biosynthesis of medicinal compounds from plants remains limited. A new study has deciphered the complete metabolic pathway leading to the biosynthesis of the psychedelic mescaline in the cactus peyote, suggesting the development of biotechnological strategies for a sustainable supply of this important plant drug., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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28. Insights into dammarane-type triterpenoid saponin biosynthesis from the telomere-to-telomere genome of Gynostemma pentaphyllum.
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Yun L, Zhang C, Liang T, Tian Y, Ma G, Courdavault V, Sun S, Ma B, Li Z, Li R, Cao F, Shen X, Wei J, Li Y, Guo B, and Sun C
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- Telomere genetics, Dammaranes, Genome, Plant, Gynostemma genetics, Gynostemma metabolism, Triterpenes metabolism, Saponins biosynthesis, Saponins genetics
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- 2024
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29. Metabolic engineering of the paclitaxel anticancer drug.
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Oudin A, Papon N, and Courdavault V
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- Humans, Antineoplastic Agents therapeutic use, Antineoplastic Agents pharmacology, Paclitaxel pharmacology, Metabolic Engineering methods
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- 2024
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30. ROP GTPases with a geranylgeranylation motif modulate alkaloid biosynthesis in Catharanthus roseus.
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Pedenla Bomzan D, Sharma A, Lemos Cruz P, Carqueijeiro I, Bellenger L, Rai A, Thippesh AK, Chinnegowda VS, Parihar D, Ducos E, Courdavault V, and Nagegowda DA
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- Protein Prenylation, Amino Acid Motifs, Alkaloids metabolism, Alkaloids biosynthesis, Catharanthus genetics, Catharanthus metabolism, Catharanthus enzymology, Plant Proteins metabolism, Plant Proteins genetics, Gene Expression Regulation, Plant
- Abstract
Rho of Plant (ROP) GTPases function as molecular switches that control signaling processes essential for growth, development, and defense. However, their role in specialized metabolism is poorly understood. Previously, we demonstrated that inhibition of protein geranylgeranyl transferase (PGGT-I) negatively impacts the biosynthesis of monoterpene indole alkaloids (MIA) in Madagascar periwinkle (Catharanthus roseus), indicating the involvement of prenylated proteins in signaling. Here, we show through biochemical, molecular, and in planta approaches that specific geranylgeranylated ROPs modulate C. roseus MIA biosynthesis. Among the six C. roseus ROP GTPases (CrROPs), only CrROP3 and CrROP5, having a C-terminal CSIL motif, were specifically prenylated by PGGT-I. Additionally, their transcripts showed higher expression in most parts than other CrROPs. Protein-protein interaction studies revealed that CrROP3 and CrROP5, but not ΔCrROP3, ΔCrROP5, and CrROP2 lacking the CSIL motif, interacted with CrPGGT-I. Further, CrROP3 and CrROP5 exhibited nuclear localization, whereas CrROP2 was localized to the plasma membrane. In planta functional studies revealed that silencing of CrROP3 and CrROP5 negatively affected MIA biosynthesis, while their overexpression upregulated MIA formation. In contrast, silencing and overexpression of CrROP2 had no effect on MIA biosynthesis. Moreover, overexpression of ΔCrROP3 and ΔCrROP5 mutants devoid of sequence coding for the CSIL motif failed to enhance MIA biosynthesis. These results implicate that CrROP3 and CrROP5 have a positive regulatory role on MIA biosynthesis and thus shed light on how geranylgeranylated ROP GTPases mediate the modulation of specialized metabolism in C. roseus., Competing Interests: Conflict of interest statement. Authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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31. Unlocking plant bioactive pathways: omics data harnessing and machine learning assisting.
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Durand M, Besseau S, Papon N, and Courdavault V
- Subjects
- Biological Products metabolism, Biosynthetic Pathways genetics, Genomics methods, Machine Learning, Plants metabolism, Plants genetics, Metabolomics methods
- Abstract
Plant bioactives hold immense potential in the medicine and food industry. The recent advancements in omics applied in deciphering specialized metabolic pathways underscore the importance of high-quality genome releases and the wealth of data in metabolomics and transcriptomics. While harnessing data, whether integrated or standalone, has proven successful in unveiling plant natural product (PNP) biosynthetic pathways, the democratization of machine learning in biology opens exciting new opportunities for enhancing the exploration of these pathways. This review highlights the recent breakthroughs in disrupting plant-specialized biosynthetic pathways through the utilization of omics data harnessing and machine learning techniques., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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32. Emerging trends in production of plant natural products and new-to-nature biopharmaceuticals in yeast.
- Author
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Perrot T, Marc J, Lezin E, Papon N, Besseau S, and Courdavault V
- Subjects
- Plants metabolism, Biotechnology methods, Synthetic Biology, Yeasts metabolism, Metabolic Engineering methods, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae genetics, Humans, Biological Products metabolism
- Abstract
Natural products represent an inestimable source of valuable compounds for human health. Notably, those produced by plants remain challenging to access due to their low production. Potential shortages of plant-derived biopharmaceuticals caused by climate change or pandemics also regularly tense the market trends. Thus, biotechnological alternatives of supply based on synthetic biology have emerged. These innovative strategies mostly rely on the use of engineered microbial systems for compound synthesis. In this regard, yeasts remain the easiest-tractable eukaryotic models and a convenient chassis for reconstructing whole biosynthetic routes for the heterologous production of plant-derived metabolites. Here, we highlight the recent discoveries dedicated to the bioproduction of new-to-nature compounds in yeasts and provide an overview of emerging strategies for optimising bioproduction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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33. Yeast Platforms for Production and Screening of Bioactive Derivatives of Rauwolscine.
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Bradley SA, Hansson FG, Lehka BJ, Rago D, Pinho P, Peng H, Adhikari KB, Haidar AK, Hansen LG, Volkova D, Holtz M, Muyo Abad S, Ma X, Koudounas K, Besseau S, Gautron N, Mélin C, Marc J, Birer Williams C, Courdavault V, Jensen ED, Keasling JD, Zhang J, and Jensen MK
- Subjects
- Humans, Biosynthetic Pathways, Yohimbine metabolism, Yohimbine pharmacology, Secologanin Tryptamine Alkaloids metabolism, Indole Alkaloids metabolism, Drug Discovery methods, Saccharomyces cerevisiae metabolism
- Abstract
Monoterpene indole alkaloids (MIAs) make up a highly bioactive class of metabolites produced by a range of tropical and subtropical plants. The corynanthe-type MIAs are a stereochemically complex subclass with therapeutic potential against a large number of indications including cancer, psychotic disorders, and erectile dysfunction. Here, we report yeast-based cell factories capable of de novo production of corynanthe-type MIAs rauwolscine, yohimbine, tetrahydroalstonine, and corynanthine. From this, we demonstrate regioselective biosynthesis of 4 fluorinated derivatives of these compounds and de novo biosynthesis of 7-chlororauwolscine by coexpression of a halogenase with the biosynthetic pathway. Finally, we capitalize on the ability of these cell factories to produce derivatives of these bioactive scaffolds to establish a proof-of-principle drug discovery pipeline in which the corynanthe-type MIAs are screened for bioactivity on human drug targets, expressed in yeast. In doing so, we identify antagonistic and agonistic behavior against the human adrenergic G protein-coupled receptors ADRA2A and ADRA2B, and the serotonergic receptor 5HT4b, respectively. This study thus demonstrates a proto-drug discovery pipeline for bioactive plant-inspired small molecules based on one-pot biocatalysis of natural and new-to-nature corynanthe-type MIAs in yeast.
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- 2024
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34. Metabolic engineering of plant medicines.
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Courdavault V and Papon N
- Subjects
- Synthetic Biology, Metabolic Engineering, Plants genetics, Plants metabolism
- Published
- 2024
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35. A chromosome-scale genome assembly of Rauvolfia tetraphylla facilitates identification of the complete ajmaline biosynthetic pathway.
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Lezin E, Carqueijeiro I, Cuello C, Durand M, Jansen HJ, Vergès V, Birer Williams C, Oudin A, Dugé de Bernonville T, Petrignet J, Celton N, St-Pierre B, Papon N, Sun C, Dirks RP, O'Connor SE, Jensen MK, Besseau S, and Courdavault V
- Subjects
- Ajmaline metabolism, Biosynthetic Pathways genetics, Rauwolfia genetics, Rauwolfia metabolism
- Published
- 2024
- Full Text
- View/download PDF
36. Accessing natural vaccine adjuvants.
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Courdavault V and Papon N
- Subjects
- Adjuvants, Immunologic pharmacology, Adjuvants, Vaccine, Vaccines
- Published
- 2024
- Full Text
- View/download PDF
37. The Madagascar palm genome provides new insights on the evolution of Apocynaceae specialized metabolism.
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Cuello C, Jansen HJ, Abdallah C, Zamar Mbadinga DL, Birer Williams C, Durand M, Oudin A, Papon N, Giglioli-Guivarc'h N, Dirks RP, Jensen MK, O'Connor SE, Besseau S, and Courdavault V
- Abstract
Specialized metabolites possess diverse interesting biological activities and some cardenolides- and monoterpene indole alkaloids- (MIAs) derived pharmaceuticals are currently used to treat human diseases such as cancers or hypertension. While these two families of biocompounds are produced by specific subfamilies of Apocynaceae , one member of this medicinal plant family, the succulent tree Pachypodium lamerei Drake (also known as Madagascar palm), does not produce such specialized metabolites. To explore the evolutionary paths that have led to the emergence and loss of cardenolide and MIA biosynthesis in Apocynaceae , we sequenced and assembled the P. lamerei genome by combining Oxford Nanopore Technologies long-reads and Illumina short-reads. Phylogenomics revealed that, among the Apocynaceae whose genomes have been sequenced, the Madagascar palm is so far the species closest to the common ancestor between MIA producers/non-MIA producers. Transposable elements, constituting 72.48% of the genome, emerge as potential key players in shaping genomic architecture and influencing specialized metabolic pathways. The absence of crucial MIA biosynthetic genes such as strictosidine synthase in P. lamerei and non- Rauvolfioideae species hints at a transposon-mediated mechanism behind gene loss. Phylogenetic analysis not only showcases the evolutionary divergence of specialized metabolite biosynthesis within Apocynaceae but also underscores the role of transposable elements in this intricate process. Moreover, we shed light on the low conservation of enzymes involved in the final stages of MIA biosynthesis in the distinct MIA-producing plant families, inferring independent gains of these specialized enzymes along the evolution of these medicinal plant clades. Overall, this study marks a leap forward in understanding the genomic dynamics underpinning the evolution of specialized metabolites biosynthesis in the Apocynaceae family, with transposons emerging as potential architects of genomics restructuring and gene loss., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Vincent Courdavault reports financial support was provided by Horizon Europe. Michael Krogh Jensen reports a relationship with BioMIA that includes: board membership and employment. Ron Dirks reports a relationship with Future Genomics Technologies that includes: board membership and employment. Hans Jensen reports a relationship with Future Genomics Technologies that includes: board membership and employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
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- 2024
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38. SPOTLIGHT: Alpha carbonic anhydrases join the club of alkaloid biosynthetic enzymes.
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Zamar DL, Papon N, and Courdavault V
- Subjects
- Carbonic Anhydrases, Alkaloids
- Abstract
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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- 2024
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- View/download PDF
39. Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast.
- Author
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Bradley SA, Lehka BJ, Hansson FG, Adhikari KB, Rago D, Rubaszka P, Haidar AK, Chen L, Hansen LG, Gudich O, Giannakou K, Lengger B, Gill RT, Nakamura Y, de Bernonville TD, Koudounas K, Romero-Suarez D, Ding L, Qiao Y, Frimurer TM, Petersen AA, Besseau S, Kumar S, Gautron N, Melin C, Marc J, Jeanneau R, O'Connor SE, Courdavault V, Keasling JD, Zhang J, and Jensen MK
- Subjects
- Monoterpenes metabolism, Indole Alkaloids metabolism, Plants metabolism, Pharmaceutical Preparations metabolism, Plant Proteins metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, Catharanthus
- Abstract
Monoterpenoid indole alkaloids (MIAs) represent a large class of plant natural products with marketed pharmaceutical activities against a wide range of indications, including cancer, malaria and hypertension. Halogenated MIAs have shown improved pharmaceutical properties; however, synthesis of new-to-nature halogenated MIAs remains a challenge. Here we demonstrate a platform for de novo biosynthesis of two MIAs, serpentine and alstonine, in baker's yeast Saccharomyces cerevisiae and deploy it to systematically explore the biocatalytic potential of refactored MIA pathways for the production of halogenated MIAs. From this, we demonstrate conversion of individual haloindole derivatives to a total of 19 different new-to-nature haloserpentine and haloalstonine analogs. Furthermore, by process optimization and heterologous expression of a modified halogenase in the microbial MIA platform, we document de novo halogenation and biosynthesis of chloroalstonine. Together, this study highlights a microbial platform for enzymatic exploration and production of complex natural and new-to-nature MIAs with therapeutic potential., (© 2023. The Author(s).)
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- 2023
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40. The Rauvolfia tetraphylla genome suggests multiple distinct biosynthetic routes for yohimbane monoterpene indole alkaloids.
- Author
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Stander EA, Lehka B, Carqueijeiro I, Cuello C, Hansson FG, Jansen HJ, Dugé De Bernonville T, Birer Williams C, Vergès V, Lezin E, Lorensen MDBB, Dang TT, Oudin A, Lanoue A, Durand M, Giglioli-Guivarc'h N, Janfelt C, Papon N, Dirks RP, O'connor SE, Jensen MK, Besseau S, and Courdavault V
- Subjects
- Monoterpenes, Indole Alkaloids metabolism, Rauwolfia genetics, Rauwolfia metabolism
- Abstract
Monoterpene indole alkaloids (MIAs) are a structurally diverse family of specialized metabolites mainly produced in Gentianales to cope with environmental challenges. Due to their pharmacological properties, the biosynthetic modalities of several MIA types have been elucidated but not that of the yohimbanes. Here, we combine metabolomics, proteomics, transcriptomics and genome sequencing of Rauvolfia tetraphylla with machine learning to discover the unexpected multiple actors of this natural product synthesis. We identify a medium chain dehydrogenase/reductase (MDR) that produces a mixture of four diastereomers of yohimbanes including the well-known yohimbine and rauwolscine. In addition to this multifunctional yohimbane synthase (YOS), an MDR synthesizing mainly heteroyohimbanes and the short chain dehydrogenase vitrosamine synthase also display a yohimbane synthase side activity. Lastly, we establish that the combination of geissoschizine synthase with at least three other MDRs also produces a yohimbane mixture thus shedding light on the complex mechanisms evolved for the synthesis of these plant bioactives., (© 2023. The Author(s).)
- Published
- 2023
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41. Medicinal plants enter the single-cell multi-omics era.
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Burlat V, Papon N, and Courdavault V
- Abstract
Elucidating biosynthetic pathways of plant specialized metabolites is a tricky but essential task for the biotechnological production of plant drugs. In a new report, Li et al. used a single-cell multi-omics approach to provide an integrative view of the architecture and regulation of anticancer alkaloid routes in Madagascar periwinkle., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
42. The Evolutionary Pattern of Cocaine and Hyoscyamine Biosynthesis Provides Strategies To Produce Tropane Alkaloids.
- Author
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Zamar DL, Papon N, and Courdavault V
- Subjects
- Tropanes chemistry, Tropanes metabolism, Cholinergic Antagonists metabolism, Hyoscyamine, Cocaine metabolism, Solanaceae metabolism
- Abstract
Cocaine and hyoscyamine are two tropane alkaloids (TA) from Erythroxylaceae and Solanaceae, respectively. These famous compounds possess anticholinergic properties that can be used to treat neuromuscular disorders. While the hyoscyamine biosynthetic pathway has been fully elucidated allowing its de novo synthesis in yeast, the cocaine pathway remained only partially elucidated. Recently, the Huang research group has completed the cocaine biosynthetic route by characterizing its two missing enzymes. This allowed the whole pathway to be transferring into Nicotiana benthamiana to achieve cocaine production. Here, besides highlighting the impact of this discovery, we discuss how TA biosynthesis evolved via the recruitment of two distinct and convergent pathways in Erythroxylaceae and Solanaceae. Finally, while enriching our knowledge on TA biosynthesis, this diversification of the molecular actors involved in cocaine and hyoscyamine biosynthesis opens perspectives in metabolic engineering by exploring enzyme biochemical plasticity that can ease and shorten TA pathway reconstitution in heterologous organisms., (© 2023 Wiley-VCH GmbH.)
- Published
- 2023
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- View/download PDF
43. Terroir Influence on Polyphenol Metabolism from Grape Canes: A Spatial Metabolomic Study at Parcel Scale.
- Author
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Billet K, Salvador-Blanes S, Dugé De Bernonville T, Delanoue G, Hinschberger F, Oudin A, Courdavault V, Pichon O, Besseau S, Leturcq S, Giglioli-Guivarc'h N, and Lanoue A
- Subjects
- Polyphenols metabolism, Reproducibility of Results, Metabolomics, Soil, Vitis metabolism
- Abstract
The composition of bioactive polyphenols from grape canes, an important viticultural byproduct, was shown to be varietal-dependent; however, the influence of soil-related terroir factors remains unexplored. Using spatial metabolomics and correlation-based networks, we investigated how continuous changes in soil features and topography may impact the polyphenol composition in grape canes. Soil properties, topography, and grape cane extracts were analyzed at georeferenced points over 3 consecutive years, followed by UPLC-DAD-MS-based metabolomic analysis targeting 42 metabolites. Principal component analyses on intra-vintage metabolomic data presented a good reproducibility in relation to geographic coordinates. A correlation-driven approach was used to explore the combined influence of soil and topographic variables on metabolomic responses. As a result, a metabolic cluster including flavonoids was correlated with elevation and curvature. Spatial metabolomics driven by correlation-based networks represents a powerful approach to spatialize field-omics data and may serve as new field-phenotyping tool in precision agriculture.
- Published
- 2023
- Full Text
- View/download PDF
44. Spatial localization of monoterpenoid indole alkaloids in Rauvolfia tetraphylla by high resolution mass spectrometry imaging.
- Author
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Lorensen MDBB, Bjarnholt N, St-Pierre B, Heinicke S, Courdavault V, O'Connor S, and Janfelt C
- Subjects
- Reserpine chemistry, Reserpine metabolism, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tryptamines metabolism, Antihypertensive Agents, Indole Alkaloids metabolism, Spectrometry, Mass, Electrospray Ionization methods, Secologanin Tryptamine Alkaloids chemistry, Rauwolfia metabolism
- Abstract
Monoterpenoid indole alkaloids (MIAs) are a large group of biosynthetic compounds, which have pharmacological properties. One of these MIAs, reserpine, was discovered in the 1950s and has shown properties as an anti-hypertension and anti-microbial agent. Reserpine was found to be produced in various plant species within the genus of Rauvolfia. However, even though its presence is well known, it is still unknown in which tissues Rauvolfia produce reserpine and where the individual steps in the biosynthetic pathway take place. In this study, we explore how matrix assisted laser desorption ionization (MALDI) and desorption electrospray ionization (DESI) mass spectrometry imaging (MSI) can be used in the investigation of a proposed biosynthetic pathway by localizing reserpine and the theoretical intermediates of it. The results show that ions corresponding to intermediates of reserpine were localized in several of the major parts of Rauvolfia tetraphylla when analyzed by MALDI- and DESI-MSI. In stem tissue, reserpine and many of the intermediates were found compartmentalized in the xylem. For most samples, reserpine itself was mainly found in the outer layers of the sample, suggesting it may function as a defense compound. To further confirm the place of the different metabolites in the reserpine biosynthetic pathway, roots and leaves of R. tetraphylla were fed a stable-isotope labelled version of the precursor tryptamine. Subsequently, several of the proposed intermediates were detected in the normal version as well as in the isotope labelled versions, confirming that they were synthesized in planta from tryptamine. In this experiment, a potential novel dimeric MIA was discovered in leaf tissue of R. tetraphylla. The study constitutes to date the most comprehensive spatial mapping of metabolites in the R. tetraphylla plant. In addition, the article also contains new illustrations of the anatomy of R. tetraphylla., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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- View/download PDF
45. Convergent evolution for antibiotic biosynthesis in bacteria and animals.
- Author
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Papon N, Courdavault V, and Medema MH
- Subjects
- Animals, Bacteria genetics, Anti-Bacterial Agents
- Abstract
Convergent evolution has been described for several metabolic pathways across the kingdoms of life. However, there is hitherto no evidence for such an interkingdom process for antimicrobials. A new report suggests that marine animals have evolved the ability to biosynthesize antimicrobial polyketides, in parallel with bacteria., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
46. Gaining access to acetyl-CoA by peroxisomal surface display.
- Author
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Perrot T, Besseau S, Papon N, and Courdavault V
- Abstract
Synthetic biology is constantly making progress for producing compounds on demand. Recently, Yocum and collaborators have developed an outstanding approach based on the anchoring of biosynthetic enzymes to the peroxisomal membrane. This allowed access to an untapped resource of acetyl-CoA and stimulated the synthesis of a valuable polyketide., Competing Interests: The authors declare no conflict of interest, and all the authors approved the submission., (© 2023 The Authors.)
- Published
- 2023
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- View/download PDF
47. Identification of a second 16-hydroxytabersonine-O-methyltransferase suggests an evolutionary relationship between alkaloid and flavonoid metabolisms in Catharanthus roseus.
- Author
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Lemos Cruz P, Carqueijeiro I, Koudounas K, Bomzan DP, Stander EA, Abdallah C, Kulagina N, Oudin A, Lanoue A, Giglioli-Guivarc'h N, Nagegowda DA, Papon N, Besseau S, Clastre M, and Courdavault V
- Subjects
- Gene Expression Regulation, Plant, Methyltransferases genetics, Methyltransferases metabolism, Phylogeny, Plant Proteins genetics, Plant Proteins metabolism, Protein Isoforms genetics, Alkaloids metabolism, Antineoplastic Agents, Catharanthus
- Abstract
The medicinal plant Catharanthus roseus biosynthesizes many important drugs for human health, including the anticancer monoterpene indole alkaloids (MIAs) vinblastine and vincristine. Over the past decades, the continuous increase in pharmaceutical demand has prompted several research groups to characterize MIA biosynthetic pathways for considering future metabolic engineering processes of supply. In line with previous work suggesting that diversification can potentially occur at various steps along the vindoline branch, we were here interested in investigating the involvement of distinct isoforms of tabersonine-16-O-methyltransferase (16OMT) which plays a pivotal role in the MIA biosynthetic pathway. By combining homology searches based on the previously characterized 16OMT1, phylogenetic analyses, functional assays in yeast, and biochemical and in planta characterizations, we identified a second isoform of 16OMT, referred to as 16OMT2. 16OMT2 appears to be a multifunctional enzyme working on both MIA and flavonoid substrates, suggesting that a constrained evolution of the enzyme for accommodating the MIA substrate has probably occurred to favor the apparition of 16OMT2 from an ancestral specific flavonoid-O-methyltransferase. Since 16OMT1 and 16OMT2 displays a high sequence identity and similar kinetic parameters for 16-hydroxytabersonine, we postulate that 16OMT1 may result from a later 16OMT2 gene duplication accompanied by a continuous neofunctionalization leading to an almost complete loss of flavonoid O-methyltransferase activity. Overall, these results participate in increasing our knowledge on the evolutionary processes that have likely led to enzyme co-optation for MIA synthesis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
48. Emerging mechanistic insights into the regulation of specialized metabolism in plants.
- Author
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Méteignier LV, Nützmann HW, Papon N, Osbourn A, and Courdavault V
- Subjects
- Metabolic Networks and Pathways, Plants, Medicinal genetics
- Abstract
Plants biosynthesize a broad range of natural products through specialized and species-specific metabolic pathways that are fuelled by core metabolism, together forming a metabolic network. Specialized metabolites have important roles in development and adaptation to external cues, and they also have invaluable pharmacological properties. A growing body of evidence has highlighted the impact of translational, transcriptional, epigenetic and chromatin-based regulation and evolution of specialized metabolism genes and metabolic networks. Here we review the forefront of this research field and extrapolate to medicinal plants that synthetize rare molecules. We also discuss how this new knowledge could help in improving strategies to produce useful plant-derived pharmaceuticals., (© 2022. Springer Nature Limited.)
- Published
- 2023
- Full Text
- View/download PDF
49. An updated version of the Madagascar periwinkle genome.
- Author
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Cuello C, Stander EA, Jansen HJ, Dugé De Bernonville T, Oudin A, Birer Williams C, Lanoue A, Giglioli Guivarc'h N, Papon N, Dirks RP, Jensen MK, O'Connor SE, Besseau S, and Courdavault V
- Subjects
- Genome, Plant, Catharanthus genetics, Catharanthus metabolism, Plants, Medicinal genetics, Plants, Medicinal metabolism
- Abstract
The Madagascar periwinkle, Catharanthus roseus , belongs to the Apocynaceae family. This medicinal plant, endemic to Madagascar, produces many important drugs including the monoterpene indole alkaloids (MIA) vincristine and vinblastine used to treat cancer worldwide. Here, we provide a new version of the C. roseus genome sequence obtained through the combination of Oxford Nanopore Technologies long-reads and Illumina short-reads. This more contiguous assembly consists of 173 scaffolds with a total length of 581.128 Mb and an N50 of 12.241 Mb. Using publicly available RNAseq data, 21,061 protein coding genes were predicted and functionally annotated. A total of 42.87% of the genome was annotated as transposable elements, most of them being long-terminal repeats. Together with the increasing access to MIA-producing plant genomes, this updated version should ease evolutionary studies leading to a better understanding of MIA biosynthetic pathway evolution., Competing Interests: Competing interests: Ron P. Dirks and Hans J. Jansen are CEO and CTO of Future Genomics Technologies, respectively., (Copyright: © 2022 Cuello C et al.)
- Published
- 2022
- Full Text
- View/download PDF
50. Boosting lignan-precursor synthesis in yeast cell factories through co-factor supply optimization.
- Author
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Perrin J, Besseau S, Papon N, and Courdavault V
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2022
- Full Text
- View/download PDF
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