Biosynthesis of the labdane diterpene marrubiin in <i>Marrubium vulgare</i> via a non-mevalonate pathway

Knöß, Werner; Reuter, Bernd; Zapp, Josef

doi:10.1042/bj3260449

Cited by 82 publications

(36 citation statements)

References 17 publications

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“…5,12,[16][17][18][19][20][21][22][23] The prenylation of the phydroxybenzoic acid involved in the formation of the chromenes 1 and 2 occurred via MEP pathway, suggesting that it is compartmentalized in the plastid. On the other hand, the second prenylation step would be occurred in the cytosol by MVA pathway.…”

Section: Discussionmentioning

confidence: 99%

Biosynthetic origin of the isoprene units in chromenes of Piper aduncum (Piperaceae)

Leite¹,

Lopes²,

Kato

et al. 2007

J. Braz. Chem. Soc.

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Estudos metabólicos envolvendo a incorporação de D-glicose-[1-13 C] em folhas dePiper aduncum (Piperaceae) mostraram que as vias do mevalonato (MVA) e da triose-piruvato (MEP) estão envolvidas na biossíntese da unidade isoprênica presente no 2,2-dimetil-2H-1-cromeno-6-carboxilato de metila (1) e no 2,2-dimetil-8-(3'-metil-2'-butenil)-2H-1-cromeno-6-carboxilato de metila (2). O padrão de incorporação dos carbonos marcados com D-glicose-[1-13 C] destes cromenos foram determinados através de espectroscopia de RMN de 13 C quantitativo. Os resultados confirmaram que o compartimento biossintético de 1 e 2 pode ser o plastídio e/ou citosol, ou possivelmente um compartimento adicional, como o espaço entre a membrana e o plastídio.Metabolic studies involving the incorporation of [1-13 C]-D-glucose into intact leaves of Piper aduncum (Piperaceae) have indicated that both the mevalonate (MVA) and the pyruvate-triose (MEP) non-mevalonate pathways are implicated in the biosynthesis of isoprene moieties present in methyl 2,2-dimethyl-2H-1-chromene-6-carboxylate (1) and methyl 2,2-dimethyl-8-(3'-methyl-2'-butenyl)-2H-1-chromene-6-carboxylate (2). The pattern of incorporation of label from [1- 13C]-D-glucose into these chromenes was determined by quantitative 13 C NMR spectroscopy. The results confirmed that biosynthetic compartment of 1 and 2 could either be the plastid and/ or the cytosol or, possibly, an additional compartment such as the plastid inter-membrane space. Keywords:Piper aduncum, chromenes, [1-13 C]-D-glucose, mevalonate pathway, 2-C-methyl-D-erythritol-4-phosphate pathway IntroductionThe isoprenoids constitute a large class of natural products comprising more than 29,000 compounds. 1 In higher plants, isoprenoids play essential roles in membrane structure (sterols), redox chemistry (plastoquinones, ubiquinones), growth regulation (gibberellins, cytokinins, brassinosteroids and abscisic acid), defence mechanisms (phytoalexins) and free radical scavenging (carotenoids and tocopherols). 2 The common building blocks of all isoprenoids, the so-called 'isoprene units', is derived from isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). The biosynthesis of IPP can proceed via two different pathways, namely the longestablished mevalonic acid (MVA) and the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathways, the reaction sequence of which has been characterized. 3 In plants, the MEP pathway appears generally operative for formation of monoterpenoids, diterpenoids, phytols and carotenoids. [4][5][6] The key regulatory step of the MVA pathway involves reduction of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) to mevalonate, with this being catalysed by the cytosolic enzyme HMG-CoA reductase (HMGR). Plastidic IPP is derived, however, from MEP formed via the condensation of pyruvate and glyceraldehyde-3-phosphate (G3P) catalysed by 1-deoxy-D-xylulose-5-phosphate synthase (DXS). 2,6 The two pathways to IPP are thus compartmentalized in the cytosol and the plastid, respectively. However, they may function in the for...

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Section: Discussionmentioning

confidence: 99%

Biosynthetic origin of the isoprene units in chromenes of Piper aduncum (Piperaceae)

Leite¹,

Lopes²,

Kato

et al. 2007

J. Braz. Chem. Soc.

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“…More recently, incorporation of 13 C-labeled Glc into plant cells (Eisenreich et al, 1996;Schwender et al, 1996;Arigoni et al, 1997;Knö ss et al, 1997;Lichtenthaler et al, 1997b) followed by NMR analysis led to new insights about the conversion of carbohydrate precursors into IPP. The new pathway proposes the condensation between the C2 unit from pyruvate and the C3 acceptor glyceraldehyde-3-phosphate to yield deoxy-xylulose phosphate, the nonmevalonic precursor of IPP Arigoni et al, 1997).…”

Section: The Role Of Transketolase In Generating Carbon-carbon Condenmentioning

confidence: 99%

“…Despite a long debate, a conclusive demonstration of mevalonic acid pathway reactions in plastids was still lacking (Gray, 1987). In vivo studies using 13 C-Glc labeling subsequently revealed the existence of an alternative nonmevalonic acid pathway for IPP synthesis in prokaryotes (Flesch and Rohmer, 1988;Rohmer et al, 1993Rohmer et al, , 1996 and in plants (Schwender et al, 1996;Arigoni et al, 1997;Knö ss et al, 1997;Lichtenthaler et al, 1997aLichtenthaler et al, , 1997b, which is initiated by a transketolation mechanism. We have characterized two pepper plastid transketolases, CapTKT1 and CapTKT2, and showed that they possess distinct specificities.…”

Section: Dedicated Roles Of Plastid Transketolasesmentioning

confidence: 99%

Dedicated Roles of Plastid Transketolases during the Early Onset of Isoprenoid Biogenesis in Pepper Fruits1

et al. 1998

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Isopentenyl diphosphate (IPP), which is produced from mevalonic acid or other nonmevalonic substrates, is the universal precursor of isoprenoids in nature. Despite the presence of several isoprenoid compounds in plastids, enzymes of the mevalonate pathway leading to IPP formation have never been isolated or identified to our knowledge. We now describe the characterization of two pepper (Capsicum annuum L.) cDNAs, CapTKT1 and CapTKT2, that encode transketolases having distinct and dedicated specificities. CapTKT1 is primarily involved in plastidial pentose phosphate and glycolytic cycle integration, whereas CapTKT2 initiates the synthesis of isoprenoids in plastids via the nonmevalonic acid pathway. From pyruvate and glyceraldehyde-3-phosphate, CapTKT2 catalyzes the formation of 1-deoxy-xylulose-5-phosphate, the IPP precursor. CapTKT1 is almost constitutively expressed during the chloroplast-to-chromoplast transition, whereas CapTKT2 is overexpressed during this period, probably to furnish the IPP necessary for increased carotenoid biosynthesis. Because deoxy-xylulose phosphate is shared by the plastid pathways of isoprenoid, thiamine (vitamin B 1 ), and pyridoxine (vitamin B 6 ) biosynthesis, our results may explain why albino phenotypes usually occur in thiaminedeficient plants.Because of the combined activities of mevalonatesynthesizing and -activating enzymes, IPP is known as the universal isoprenoid building block. How IPP is synthesized and channeled into plastid isoprenoids to support the production of carotenoids, chlorophylls, prenylquinones, and diterpenes is largely unknown. Two hypotheses have been proposed. One is that plastids operate autonomously, synthesizing plastid isoprenoids directly from carbon dioxide or from plastid glycolytic intermediates such as pyruvate (Goodwin, 1971;Moore and Shephard, 1978; Heintze et al., 1990 Heintze et al., , 1994McCaskill and Croteau, 1995). However, the mechanism of carbon flow via a pyruvate intermediate is unknown for plants. A second hypothesis is that IPP is transported from the cytosol (Kleinig, 1989), which is based on the finding that hydroxymethylglutaryl CoA reductase and mevalonate-activating enzymes are absent in plastids (Gray, 1987). This view is reinforced by the fact that mevilonin, a specific inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, drastically inhibits cytosolic sterol biosynthesis at moderate concentrations but does not affect isoprenoid synthesis in plastids (Bach and Lichtenthaler, 1983). This led to consideration of an alternative IPP-generation system. In fact, such a pathway is known for prokaryotes, in which IPP is formed via deoxy-xylulose phosphate rather than by mevalonate (Rohmer et al., 1993) in a transketolation reaction between pyruvate and glyceraldehyde-3-phosphate . In vivo precursor labeling indicates that a similar pathway operates for the synthesis of ginkgolides (Schwarz, 1994) and plastid isoprenoids (Schwender et al., 1996; Arigoni et al., 1997;Lichtenthaler et al., 1997aLichtenthaler et al., , 1997b.In t...

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“…la, see e.g. [1]), and an alternative mevalonate independent biosynthetic route unravelled by 13 C-incorporation studies in bacteria [2], green algae [3][4][5][6][7][8], and higher plants [6,[8][9][10][11][12][13]. In fact, in higher plants and green algae the biosynthesis of all plastidic isoprenoids such as the phytyl side chain of chlorophylls, the carotenoids and the nonaprenyl side chain of plastoquinone-9 [3][4][5]12] appears to follow this alternative route, of which the elucidation of the distinct biosynthetic steps is just at the beginning.…”

Section: Introductionmentioning

confidence: 99%

Incorporation of 1‐deoxy‐d‐xylulose into isoprene and phytol by higher plants and algae

et al. 1997

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In further substantiating the novel mevalonate-independent pathway for isoprenoid biosynthesis, which generates isopentenyl diphosphate (IPP) via l-deoxy-D-xylulose-5-phosphate, labeling experiments with l-[2 Hi]deoxy-D-xylulose were performed with various higher plants and algae: efficient incorporation was observed into isoprene emitted by Populus, Chelidonium, and Salix, into the phytol moiety of chlorophylls in a red alga (Cyanidium), in two green algae (Scenedesmus, Chlamydomonas), and a higher plant (Lemna). By contrast, 13 Cmevalonate applied was incorporated into isoprene and phytol to a much lower extent or not at all. This demonstrates that this '1-deoxy-D-xylulose-5-phosphate pathway' for biosynthesis of plastidic isoprenoids is widely distributed in photosynthetic organisms.

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Biosynthesis of the labdane diterpene marrubiin in Marrubium vulgare via a non-mevalonate pathway

Cited by 82 publications

References 17 publications

Biosynthetic origin of the isoprene units in chromenes of Piper aduncum (Piperaceae)

Biosynthetic origin of the isoprene units in chromenes of Piper aduncum (Piperaceae)

Dedicated Roles of Plastid Transketolases during the Early Onset of Isoprenoid Biogenesis in Pepper Fruits1

Incorporation of 1‐deoxy‐d‐xylulose into isoprene and phytol by higher plants and algae

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