Peroxisomal localisation of the final steps of the mevalonic acid pathway in planta

Simkin, Andrew J.; Guirimand, Grégory; Papon, Nicolas; Courdavault, Vincent; Thabet, Insaf; Ginis, Olivia; Bouzid, Sadok; Giglioli-Guivarc’h, Nathalie; Clastre, Marc

doi:10.1007/s00425-011-1444-6

Cited by 127 publications

(79 citation statements)

References 45 publications

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“…Besides plastids and the endoplasmic reticulum, postulated earlier to harbor CPTs (Skorupinska-Tudek et al, 2008), plant peroxisomes also could possess their own CPT, as was observed in mammals and yeast (Ericsson et al, 1992;Skoneczny et al, 2006). Moreover, the existence of the peroxisomal pathway converting MVA to IPP in mammals and plants (Thompson et al, 1987;Simkin et al, 2011) further supports this concept. Still, the type of all-trans-initiator involved in the biosynthesis of Dols in Arabidopsis roots remains enigmatic.…”

Section: Discussionmentioning

confidence: 74%

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis

et al. 2017

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The cooperation of the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways, operating in parallel in plants to generate isoprenoid precursors, has been studied extensively. Elucidation of the isoprenoid metabolic pathways is indispensable for the rational design of plant and microbial systems for the production of industrially valuable terpenoids. Here, we describe a new method, based on numerical modeling of mass spectra of metabolically labeled dolichols (Dols), designed to quantitatively follow the cooperation of MVA and MEP reprogrammed upon osmotic stress (sorbitol treatment) in Arabidopsis (Arabidopsis thaliana). The contribution of the MEP pathway increased significantly (reaching 100%) exclusively for the dominating Dols, while for long-chain Dols, the relative input of the MEP and MVA pathways remained unchanged, suggesting divergent sites of synthesis for dominating and long-chain Dols. The analysis of numerically modeled Dol mass spectra is a novel method to follow modulation of the concomitant activity of isoprenoid-generating pathways in plant cells; additionally, it suggests an exchange of isoprenoid intermediates between plastids and peroxisomes.Isopentenyl diphosphate (IPP), the building block of isoprenoids, the most numerous class of secondary metabolites, is derived in plants from two pathways operating in parallel: the cytoplasmic mevalonate (MVA) and the plastidic methylerythritol phosphate (MEP) pathways (Rohmer, 1999;Pulido et al., 2012).Analysis of over 130 isoprenoids has shown that, in angiosperms under standard growth conditions, carotenoids and chlorophyll phytyl chains on the one hand and phytosterols on the other are made nearly exclusively via a single pathway (MEP and MVA, respectively), while numerous other isoprenoids, including dolichols (Dols; Skorupinska-Tudek et al., 2008), are of mixed origin (Hemmerlin et al., 2012).The cooperation of the two pathways (often called cross talk) is considered essential for plant adaptive responses to biotic and abiotic stresses. Consequently, their relative contributions to the formation of IPP are modulated, and the expression of particular genes of the MVA and MEP pathways is frequently correlated with stress (pathogen attack, elicitation, wounding, etc.;Hemmerlin et al., 2012) or plant development (Opitz et al., 2014). Interestingly, the effect of stress on the regulation of the MEP-MVA balance has so far been analyzed only qualitatively.Several methodologies have been employed to unravel the relative contributions of the MVA and MEP pathways to isoprenoids, such as metabolic labeling with isotopically labeled precursors (stable isotopes or radioisotopes were used), followed by structural analysis of the product of interest or blockage of the pathway (chemical, with pathway-specific inhibitors, or genetic), followed by quantification of the isoprenoid intermediates and/or end products. The advantages

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Section: Discussionmentioning

confidence: 74%

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis

et al. 2017

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“…The last two MVA pathway enzymes, PMK and MDD, as well as isopentenyl diphosphate isomerase (IDI), catalyzing the interconversion of IPP and DMAPP, are localized in peroxisomes (16,17). To determine the site of IPK action, we established its subcellular localization.…”

Section: Ipk Is Coexpressed With the Mva Pathway And Downstream Terpementioning

confidence: 99%

Orthologs of the archaeal isopentenyl phosphate kinase regulate terpenoid production in plants

Henry

Gutensohn

Thomas

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Terpenoids, compounds found in all domains of life, represent the largest class of natural products with essential roles in their hosts. All terpenoids originate from the five-carbon building blocks, isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP), which can be derived from the mevalonic acid (MVA) and methylerythritol phosphate (MEP) pathways. The absence of two components of the MVA pathway from archaeal genomes led to the discovery of an alternative MVA pathway with isopentenyl phosphate kinase (IPK) catalyzing the final step, the formation of IPP. Despite the fact that plants contain the complete classical MVA pathway, IPK homologs were identified in every sequenced green plant genome. Here, we show that IPK is indeed a member of the plant terpenoid metabolic network. It is localized in the cytosol and is coexpressed with MVA pathway and downstream terpenoid network genes. In planta, IPK acts in parallel with the MVA pathway and plays an important role in regulating the formation of both MVA and MEP pathway-derived terpenoid compounds by controlling the ratio of IP/DMAP to IPP/DMAPP. IP and DMAP can also competitively inhibit farnesyl diphosphate synthase. Moreover, we discovered a metabolically available carbon source for terpenoid formation in plants that is accessible via IPK overexpression. This metabolite reactivation approach offers new strategies for metabolic engineering of terpenoid production.A ll living organisms produce terpenoids, directing a considerable amount of their available carbon to the biosynthesis of one of the most structurally and functionally diverse classes of primary and secondary metabolites in nature (1). These molecules play essential and specialized roles in their hosts in photosynthesis and respiration (the phytyl side-chain of chlorophyll, quinones), modulating membrane fluidity (sterols), regulating growth and development (hormones), photoprotection and energy transfer (carotenoids), and communication, environmental adaptation, and chemical defense (mono-, sesqui-, and diterpenes) (2, 3). Some compounds, like quinones, chlorophylls, and certain proteins, which require targeting to membranes for their functions, are anchored by terpenoid structures. In addition to their vital biological roles, terpenoids are also widely used by humans as nutritional supplements, flavors, fragrances, biofuels, and pharmaceuticals (4-6). Multiple metabolic pathways operate in parallel, often intersect, and routinely exchange intermediates, leading to one of the most chemically complex groups of natural products in the biosphere. Therefore, achieving a complete understanding at both genetic and biochemical levels of the underlying regulatory networks that coordinate and homeostatically govern these biosynthetic systems is of paramount importance to fully capitalize on the utility of terpenoids to natural ecosystems and humans.All terpenoids originate from C5 building blocks, isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP), which are ...

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“…In this addendum, we provide additional data describing the peroxisomal localization of 5-phosphomevalonate kinase and mevalonate 5-diphosphate decarboxylase, the last two enzymes of the mevalonic acid pathway leading to IPP. 2 This finding was reinforced in our latest report showing that a short isoform of farnesyl diphosphate, using IPP and DMAPP as substrates, is also targeted to the organelle. 3 Therefore, the classical sequestration of isoprenoid biosynthesis between plastids and cytosol/ER can be revisited by including the peroxisome as an additional isoprenoid biosynthetic compartment within plant cells.…”

mentioning

confidence: 82%

“…Thus, transient transformations of Madagascar periwinkle (Catharanthus roseus) cells with Yellow Fluorescent Protein-fused constructs revealed that the last two enzymes of the MVA pathway from Arabidopsis and C. roseus, 5-phosphomevalonate kinase (PMK) and mevalonate 5-diphosphate decarboxylase (MVD), are localized to peroxisomes. 2 Furthermore, two other C. roseus enzymes related to the MVA pathway have been shown to be targeted to this organelle: a short isoform of IDI (Courdavault, personal communication), secondary metabolite paxilline, is also targeted to the peroxisome. 9 In plants, recent studies have identified the peroxisome as an additional site for isoprenoid biosynthesis.…”

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confidence: 99%

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Subcellular evidence for the involvement of peroxisomes in plant isoprenoid biosynthesis

Clastre

Papon

Courdavault

et al. 2011

Plant Signaling & Behavior

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International audienceThe role of peroxisomes in isoprenoid metabolism, especially in plants, has been questioned in several reports. A recent study of Sapir-Mir et al. revealed that the two isoforms of isopentenyl diphosphate (IPP) isomerase, catalyzing the isomerisation of IPP to dimethylallyl diphosphate (DMAPP) are found in the peroxisome. In this addendum, we provide additional data describing the peroxisomal localization of 5-phosphomevalonate kinase and mevalonate 5-diphosphate decarboxylase, the last two enzymes of the mevalonic acid pathway leading to IPP. This finding was reinforced in our latest report showing that a short isoform of farnesyl diphosphate, using IPP and DMAPP as substrates, is also targeted to the organelle. Therefore, the classical sequestration of isoprenoid biosynthesis between plastids and cytosol/ER can be revisited by including the peroxisome as an additional isoprenoid biosynthetic compartment within plant cells

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Peroxisomal localisation of the final steps of the mevalonic acid pathway in planta

Cited by 127 publications

References 45 publications

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis

Modeling of Dolichol Mass Spectra Isotopic Envelopes as a Tool to Monitor Isoprenoid Biosynthesis

Orthologs of the archaeal isopentenyl phosphate kinase regulate terpenoid production in plants

Subcellular evidence for the involvement of peroxisomes in plant isoprenoid biosynthesis

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