Mevalonate-independent Pathway Research Articles

Synthesis of [3,5,5,5- 2H 4]-2- C-methyl- d-erythritol, a substrate designed for the elucidation of the mevalonate independent route for isoprenoid biosynthesis

2- C-Methyl- d-erythritol 4-phosphate is a key intermediate in the mevalonate independent pathway for isoprenoid biosynthesis. In order to investigate the fate of the protons in this metabolic route, [3,5,5,5- 2H 4]-2- C-methyl- d-erythritol was synthesized. The relevant steps allowing deuterium introduction were a palladium(II)-catalyzed hydrostannation and a coupling reaction between a vinyl iodide and a methylcyanocuprate.

20. 植物はアブシジン酸を非メバロン酸経路で, 糸状菌はメバロン酸経路で生合成する

20. 植物はアブシジン酸を非メバロン酸経路で, 糸状菌はメバロン酸経路で生合成する

Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs.

A mevalonate-independent pathway of isoprenoid biosynthesis present in Plasmodium falciparum was shown to represent an effective target for chemotherapy of malaria. This pathway includes 1-deoxy-D-xylulose 5-phosphate (DOXP) as a key metabolite. The presence of two genes encoding the enzymes DOXP synthase and DOXP reductoisomerase suggests that isoprenoid biosynthesis in P. falciparum depends on the DOXP pathway. This pathway is probably located in the apicoplast. The recombinant P. falciparum DOXP reductoisomerase was inhibited by fosmidomycin and its derivative, FR-900098. Both drugs suppressed the in vitro growth of multidrug-resistant P. falciparum strains. After therapy with these drugs, mice infected with the rodent malaria parasite P. vinckei were cured.

Molecular biology and regulation of abscisic acid biosynthesis in plants

The phytohormone abscisic acid (ABA) is involved in seed dormancy and the response to various environmental stresses. Our understanding of the ABA biosynthetic pathway has been increased recently through the use of plant mutants and the cloning of many of the genes encoding for the enzymes involved. C 40 Xanthophylls are precursors of ABA and are now known to be derived from isopentenyl phosphate (IPP) synthesized in plastids via a mevalonate-independent pathway. Enzyme reactions downstream of zeaxanthin have recently been reported to be important for the precise regulation of ABA levels. Zeaxanthin epoxidase (ZEP) catalyses the conversion of zeaxanthin to violaxanthin. Changes in ZEP gene expression appear to regulate ABA biosynthesis in seeds and roots, but not in leaves which might be expected considering the important role of epoxy-carotenoids in photosynthesis and photoprotection. The isomerization of the resulting all- trans-violaxanthin to 9- cis-epoxy-carotenoids awaits elucidation. Although 9- cis-epoxy-carotenoid dioxygenase (NCED), which subsequently cleaves the resulting carotenoids could use the 9- cis isomers of both violaxanthin and neoxanthin as substrates in vitro, the in vivo substrates remain to be determined. NCEDs are apparently encoded by multigene families and identification of the various members is required to determine their relative contribution to the regulation of ABA levels. Studies on those already available indicate that their up-regulation upon water stress is compatible with a key role in the modulation of ABA levels. The genes encoding for the enzymes that convert the cleavage product xanthoxin to ABA are not yet known, although recently cloned aldehyde oxidases may act on ABA-aldehyde.

Isoprenoid Biosynthesis via a Mevalonate-Independent Pathway in Plants: Cloning and Heterologous Expression of 1-Deoxy-d-xylulose-5-phosphate Reductoisomerase from Peppermint

Two distinct pathways are utilized by plants for the biosynthesis of isopentenyl diphosphate, the universal precursor of isoprenoids. The classical acetate/mevalonate pathway operates in the cytosol, whereas plastidial isoprenoids originate via a novel mevalonate-independent route that involves a transketolase-catalyzed condensation of pyruvate andd-glyceraldehyde-3-phosphate to yield 1-deoxy-d-xylulose-5-phosphate as the first intermediate. Based onin vivofeeding experiments, rearrangement and reduction of deoxyxylulose phosphate have been proposed to give rise to 2-C-methyl-d-erythritol-4-phosphate as the second intermediate of this pyruvate/glyceraldehyde-3-phosphate pathway (1–3). The cloning of anEscherichia coligene encoding an enzyme capable of converting 1-deoxy-d-xylulose-5-phosphate to 2-C-erythritol-4-phosphate was recently reported (4). A cloning strategy was developed for isolating the gene encoding a plant homolog of this enzyme from peppermint (Mentha×piperita), and the identity of the resulting cDNA was confirmed by heterologous expression inE. coli.Unlike the microbial reductoisomerase, the plant ortholog encodes a preprotein bearing an N-terminal plastidial transit peptide that directs the enzyme to plastids where the mevalonate-independent pathway operates in plants. The peppermint gene comprises an open reading frame of 1425 nucleotides which, when the plastidial targeting sequence is excluded, encodes a deduced enzyme of approximately 400 amino acid residues with a mature size of about 43.5 kDa.

Biosynthesis of furanocoumarins: mevalonate-independent prenylation of umbelliferone in Apium graveolens (Apiaceae)

Abstract Preincubation of detached leaves of Apium graveolens with deuterium labelled [5,5-2 H2]-deoxy- d -xylulose prior to the elicitation of furanocoumarin biosynthesis by jasmonic acid, resulted in high incorporation of a deuterated prenyl segment into all genuine furanocoumarins. Psoralen, xanthotoxin, bergapten and iso-pimpinellin consistently showed at C-3′ of the furan moiety the presence of a single deuterium atom (31% 2 H). With respect to previous studies, that indicated only a very low incorporation of mevalonate into furanocoumarins, our results clearly demonstrate that the prenylation of umbelliferone in A. graveolens is achieved via the novel mevalonate independent pathway. This is the first example of the participation of DOX-derived DMAPP in a prenylation reaction.

The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants.

1 Isoprenoid biosynthesis 1.1 The mevalonate route to isopentenyl diphosphate 1.2 Isoprenoid biosynthesis in higher plants: some contradictions with the mevalonate pathway 2 The discovery of the mevalonate-independent pathway 2.1 The origin of the discovery: the biosynthesis of bacterial hopanoids 2.2 The origin of the carbon atoms of isoprenic units in the mevalonate-independent pathway 2.3 d-Glyceraldehyde 3-phosphate and pyruvate as the first precursors of isopentenyl diphosphate 3 Towards the identification of intermediates and enzymes of the new pathway 3.1 1-Deoxy-d-xylulose 5-phosphate and 1-deoxy-d-xylulose 5-phosphate synthase 3.2 2-C-Methyl-d-erythritol 4-phosphate and 1-deoxy-d-xylulose 5-phosphate reducto-isomerase 4 The distribution of the glyceraldehyde 3-phosphate/pyruvate pathway amongst prokaryotes 5 The distribution of the GAP/pyruvate pathway amongst phototrophic eukaryotes 5.1 Essential plant chloroplast isoprenoids and sterols from green algae 5.2 Isoprenoids from secondary metabolism 5.3 Intermediate exchanges between the mevalonate and the GAP/pyruvate pathways in plants 6 Conclusion 7 Acknowledgments 8 References

20 Abscisic acid is biosynthesized via the mevalonate-independent pathway in plants, and via the mevalonate pathway fungi

20 Abscisic acid is biosynthesized via the mevalonate-independent pathway in plants, and via the mevalonate pathway fungi

Mevalonate-Independent Biosynthesis of Terpenoid Volatiles in Plants: Induced and Constitutive Emission of Volatiles.

Terpenoids from flower and leaf volatiles are predominantly synthesized along the mevalonate-independent pathway, as shown by administration of [D2 ]deoxy-D-xylulose and [D5 ]mevalolactone. The parallel use of two pathways for the biosynthesis of the sesquiterpenoid-derived 4,8-dimethylnona-1,3,7-triene (DMNT, see picture) may be important to ensure the synthesis of the volatile alarm codes of plants.

Mevalonate-Independent Biosynthesis of Terpenoid Volatiles in Plants: Induced and Constitutive Emission of Volatiles

Terpenoids from flower and leaf volatiles are predominantly synthesized along the mevalonate-independent pathway, as shown by administration of [D2]deoxy-D-xylulose and [D5]mevalolactone. The parallel use of two pathways for the biosynthesis of the sesquiterpenoid-derived 4,8-dimethylnona-1,3,7-triene (DMNT, see picture) may be important to ensure the synthesis of the volatile alarm codes of plants.

Incorporation of [2,3- 13C 2]- and [2,4- 13C 2]- d-1-Deoxyxylulose into Ubiquinone of Escherichia coli via the Mevalonate-Independent Pathway for Isoprenoid Biosynthesis

[2,3- 13C 2]- and [2,4- 13C 2]- d-1-deoxyxylulose were synthesized from [2- 13C]pyruvate and [1- 13C]- or [2- 13C]- dl-glyceraldehyde using the enzyme d-1-deoxyxylulose 5-phosphate synthase from Escherichia coli which was overexpressed in this bacterium. These doubly-labeled isoprenoid precursors in the mevalonate independent route were incorporated into the ubiquinone of E. coli. 1J 13C/ 13C coupling constants were respectively found in isoprenic units between carbon atoms derived from C-3 and C-4 of isopentenyl diphosphate using the former labeled precursor or between C-3 and C-2 using the latter, indicating that d-1-deoxyxylulose was incorporated without prior degradation into isoprenoids and confirming that the branched isoprenic skeleton resulted from a rearrangement of the straight chain from carbohydrate precursor. © 1997 Elsevier Science Ltd. All rights reserved.

Incorporation of 2-C-Methyl-d-erythritol, a Putative Isoprenoid Precursor in the Mevalonate-Independent Pathway, into Ubiquinone and Menaquinone of Escherichia coli

Incorporation of deuterium labelled 2-C-methyl-d-erythritol into isoprenoid side-chains of ubiquinone and menaquinone from Escherichia coli strongly supports the proposed intermediate role of this branched sugar derivative in the mevalonate independent pathway for isoprenoid biosynthesis via glyceraldehyde 3-phosphate and pyruvate. © 1997 Published by Elsevier Science Ltd.

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

In further substantiating the novel mevalonate-independent pathway for isoprenoid biosynthesis, which generates isopentenyl diphosphate (IPP) via 1-deoxy- d-xylulose-5-phosphate, labeling experiments with 1-[ 2H 1]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, 13C-mevalonate 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.

Biosynthesis of isoprenoids in higher plant chloroplasts proceeds via a mevalonate-independent pathway

Isopentenyl diphosphate (IPP) is the biological C 5 precursor of isoprenoids. By labeling experiments using [1- 13C]glucose, higher plants were shown to possess two distinct biosynthetic routes for IPP biosynthesis: while the cytoplasmic sterols were formed via the acetate/mevalonate pathway, the chloroplast-bound isoprenoids (β-carotene, lutein, prenyl chains of chlorophylls and plastoquinone-9) were synthesized via a novel IPP biosynthesis pathway (glyceraldehyde phosphate/pyruvate pathway) which was first found in eubacteria and a green alga. The dichotomy in isoprenoid biosynthesis in higher plants allows a reasonable interpretation of previous odd and inconclusive results concerning the biosynthesis of chloroplast isoprenoids, which so far had mainly been interpreted in the frame of models using compartmentation of the mevalonate pathway.