Isoprenoid biosynthesis and regulation

EA2106 Isoprenoid biosynthesis and regulation

Work of EA2106 BBV on isoprenoid metabolism is closely related to the area of focus “Architecture of MIA metabolism”.

Isoprenoids (also referred to as terpenoids) are derived from a common C5 precursor, isopentenyl diphosphate (IPP) and its allylic isomer dimethylallyl diphosphate (DMAPP). Two separate IPP forming pathways co-exist in plants: the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway provides the precursors for the synthesis of monoterpenes (and among them the monoterpenes leading to the alkaloids from Catharanthus roseus), carotenoids, apocarotenoids the side chain of chlorophylls, tocopherols and prenylquinones, while the mevalonic acid (MVA) pathway leads to precursors for the formation of triterpenes, sesquiterpenes, phytosterols, ubiquinone, vitamin D and primary metabolites important for cell integrity.


Our research is focused on the elucidation of isoprenoid biosynthesis including the MEP and MVA pathways as well as the next enzymatic steps catalyzed by prenyltransferases and terpene synthases. Moreover, the deciphering of the overall isoprenoid architecture allow us to investigate the regulatory network and to look for transcription factors that would regulate specifically isoprenoid biosynthesis pathway genes and therefore the supply of precursors for alkaloid biosynthesis.

During the past years, we established a map at the subcellular and tissular levels of the isoprenoid biosynthesis pathways highlighting the complexity of localization of isoprenoid enzymes. For example, recent subcellular studies have shown that the peroxisome is an additional isoprenoid biosynthetic compartment within plant cells. Our work also led to the characterization of isoprenoid genes and their expression regulation. We therefore isolated few transcription factors that specifically target the MEP pathway genes.

 Contact: Marc Clastre, Audrey Oudin


Chebbi, M., Ginis, O., Courdavault, V., Glévarec, G., Lanoue, A., Clastre, M., Papon, N., Gaillard, C., Atanassova, R., St-Pierre, B., Giglioli-Guivarc’h, N., Courtois, M. & Oudin, A. (2014). ZCT1 and ZCT2 transcription factors repress the activity of a gene promoter from the methyl erythritol phosphate pathway in Madagascar periwinkle cells. Journal of Plant Physiology 171, 1510-3.

Simkin, A. J., Miettinen, K., Claudel, P., Burlat, V., Guirimand, G., Courdavault, V., Papon, N., Meyer, S., Godet, S., St-Pierre, B., Giglioli-Guivarc'h, N., Fischer, M. J., Memelink, J.  & Clastre, M. (2013). Characterization of the plastidial geraniol synthase from Madagascar periwinkle which initiates the monoterpenoid branch of the alkaloid pathway in internal phloem associated parenchyma. Phytochemistry 85, 36–43.

Crouzet, J., Roland, J., Peeters, E., Trombik, T., Ducos, E., Nader, J. & Boutry, M. (2013). NtPDR1, a plasma membrane ABC transporter from Nicotiana tabacum, is involved in diterpene transport. Plant Mol Biol 82, 181–92.

Thabet, I., Guirimand, G., Guihur, A., Lanoue, A., Courdavault, V., Papon, N., Bouzid, S., Giglioli-Guivarc’h, N., Simkin, A. J. & Clastre, M. (2012). Characterization and subcellular localization of geranylgeranyl diphosphate synthase from Catharanthus roseus. Mol Biol Rep 39, 3235–43.

Guirimand, G., Simkin, A. J., Papon, N., Besseau, S., Burlat, V., St-Pierre, B., Giglioli-Guivarc’h, N., Clastre, M. & Courdavault, V. (2012a). Cycloheximide as a tool to investigate protein import in peroxisomes: a case study of the subcellular localization of isoprenoid biosynthetic enzymes. J Plant Physiol 169, 825–9.

Guirimand, G., Guihur, A., Phillips, M. A., Oudin, A., Glévarec, G., Melin, C., Papon, N., Clastre, M., St-Pierre, B., Rodríguez-Concepción, M., Burlat, V. & Courdavault, V. (2012b). A single gene encodes isopentenyl diphosphate isomerase isoforms targeted to plastids, mitochondria and peroxisomes in Catharanthus roseus. Plant Mol Biol 79, 443–59.

Ginis, O., Courdavault, V., Melin, C., Lanoue, A., Giglioli-Guivarc’h, N., St-Pierre, B., Courtois, M. & Oudin, A. (2012a). Molecular cloning and functional characterization of Catharanthus roseus hydroxymethylbutenyl 4-diphosphate synthase gene promoter from the methyl erythritol phosphate pathway. Mol Biol Rep 39, 5433–47.

Ginis, O., Oudin, A., Guirimand, G., Chebbi, M., Courdavault, V., Glévarec, G., Papon, N., Crèche, J. & Courtois, M. (2012b). A type-B response regulator drives the expression of the hydroxymethylbutenyl diphosphate synthase gene in periwinkle. J Plant Physiol  169, 1571-4.

Guirimand, G., Guihur, A., Phillips, M.A., Oudin, A., Glévarec, G., Mahroug, S., Melin, C., Papon, N., Clastre, M., Giglioli-Guivarc'h, N., St-Pierre, B., Rodríguez-Concepción, M., Burlat, V. & Courdavault, V.(2012). Triple subcellular targeting of isopentenyl diphosphate isomerases encoded by a single gene. Plant Signaling & Behavior 7,1495-7.

Thabet, I., Guirimand, G., Courdavault, V., Papon, N., Godet, S., Dutilleul, C., Bouzid, S., Giglioli-Guivarc’h, N., Clastre, M. & Simkin, A. J. (2011). The subcellular localization of periwinkle farnesyl diphosphate synthase provides insight into the role of peroxisome in isoprenoid biosynthesis. J Plant Physiol 168, 2110–6.

Simkin, A. J., Guirimand, G., Papon, N., Courdavault, V., Thabet, I., Ginis, O., Bouzid, S., Giglioli-Guivarc’h, N. & Clastre, M. (2011). Peroxisomal localisation of the final steps of the mevalonic acid pathway in planta. Planta 234, 903–14.

Clastre, M., Papon, N., Courdavault, V., Giglioli-Guivarc’h, N., St-Pierre, B. & Simkin, A. J. (2011). Subcellular evidence for the involvement of peroxisomes in plant isoprenoid biosynthesis. Plant Signal Behav 6, 2044–6.

Guirimand, G., Burlat, V., Oudin, A., Lanoue, A., St-Pierre, B. & Courdavault, V.  (2009). Optimization of the transient transformation of Catharanthus roseus cells by particle bombardment and its application to the subcellular localization of hydroxymethylbutenyl 4-diphosphate synthase and geraniol 10-hydroxylase. Plant Cell Rep 28, 1215-34.

Oudin, A., Mahroug, S., Courdavault, V., Hervouet, N., Zelwer, C., RodrĂ­guez-ConcepciĂłn, M., St-Pierre, B. & Burlat V. (2007). Spatial distribution and hormonal regulation of gene products from methyl erythritol phosphate and monoterpene-secoiridoid pathways inCatharanthus roseus. Plant Mol Biol 65, 13-30.

Oudin. A., Courtois. M., Rideau. M. & Clastre. M. (2007). The iridoid pathway in Catharanthus roseus alkaloid biosynthesis. Phytochem Rev 6, 259-76.

Papon, N., Bremer, J., Vansiri, A., Andreu, F., Rideau, M. & Crèche, J. (2005). Cytokinin and ethylene control indole alkaloid production at the level of the MEP/terpenoid pathway in Catharanthus roseus suspension cells. Planta Med 71, 572-4.

Mincheva, Z., Courtois, M., Andreu, F., Rideau, M. & Viaud-Massuard, M.-C. (2005). Fosmidomycin analogues as inhibitors of monoterpenoid indole alkaloid production in Catharanthus roseus cells. Phytochemistry 66, 1797-803.

Courtois, M., Mincheva, Z., Andreu, F., Rideau, M. & Viaud-Massuard, M.-C. (2004). Synthesis and biological evaluation with plant cells of new fosmidomycin analogues containing a benzoxazolone or oxazolopyridinone ring. J Enzyme Inhib Med Chem 19, 559-65.

Mincheva, Z., Courtois, M., Crèche, J., Rideau, M. & Viaud-Massuard M.-C. (2004). One-pot synthesis of functionalized 4,5-dihydroisoxazole derivatives via nitrile oxides and biological evaluation with plant cells. Bioorg Med Chem 12, 191-7.

Burlat, V., Oudin, A., Courtois, M., Rideau, M., & St-Pierre, B. (2004). Co-expression of three MEP pathway genes and geraniol 10-hydroxylase in internal phloem parenchyma of Catharanthus roseus implicates multicellular translocation of intermediates during the biosynthesis of monoterpene indole alkaloids and isoprenoid-derived primary metabolites. Plant J 38, 131-41.

Oudin, A., Veau, B., Courtois, M., Guivarc’h, N., Chahed, K., Chénieux, J.-C.,  Rideau, M. & Clastre, M. (2001). Architecture des voies terpéniques impliquées dans la biosynthèse des alcaloïdes chez la pervenche de Madagascar. Dans: Des modèles biologiques à l’amélioration des plantes, S. Hamon ed, p 445-464 (ISBN : 2-7099-1472-7).

Veau, B., Courtois, M., Oudin, A., Chénieux, J.-C., Rideau, M. & Clastre, M. (2000). Cloning and expression of cDNAs encoding two enzymes of the MEP pathway in Catharanthus roseus. Biochim Biophys Acta 1517, 159-63.

Chahed, K., Oudin, A., Guivarc'h, N., Hamdi, S., Chénieux, J.-C., Rideau, M. & Clastre, M. (2000). 1-deoxyxylulose-D-xylulose 5-phosphate synthase from periwinkle : cDNA identification and induced gene expression in terpenoid indole alkaloid-producing cells. Plant Physiol Biochem 38, 559-66.

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