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An overview of the non-mevalonate pathway for terpenoid biosynthesis in plants

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Abstract

Terpenoids are known to have many important biological and physiological functions. Some of them are also known for their pharmaceutical significance. In the late nineties after the discovery of a novel non-mevalonate (non-MVA) pathway, the whole concept of terpenoid biosynthesis has changed. In higher plants, the conventional acetate-mevalonate (Ac-MVA) pathway operates mainly in the cytoplasm and mitochondria and synthesizes sterols, sesquiterpenes and ubiquinones predominantly. The plastidic non-MVA pathway however synthesizes hemi-, mono-, sesqui- and di-terpenes, along with carotenoids and phytol chain of chlorophyll. In this paper, recent developments on terpenoids biosynthesis are reviewed with respect to the non-MVA pathway.

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Abbreviations

ATP:

adenosine triphosphate

CDP:

cytidine diphosphate

CDP-ME:

4-diphosphocytidyl-2-C-methyl-D-erythritol

CDP-ME2P:

4-diphosphocytidyl-2-C-methyl-D-erythritol-2-phosphate

CTP:

cytidine triphosphate

DMAPP:

dimethylal-lyl diphosphate

DOXP:

1-deoxy-D-xylulose-5-phosphate

DXS:

DOXP synthase

DXR:

DOXP reductoisomerase

FPP:

farnesyl diphosphate

GAP:

glyceraldehyde-3-phosphate

GGPP:

geranylgeranyl diphosphate

GPP:

geranyl diphosphate

HMBPP:

1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate

HMG-CoA:

3-hydroxy-3-methylglutaryl-CoA

HMGR:

3-hydroxy-3-methylglutaryl-CoA reductase

IPP:

isopentenyl diphosphate

MECP:

2C-methyl-D-erythritol 2, 4-cyclodiphosphate

MEP:

2-C-methyl-D-erythritol-4-phosphate

MVA:

mevalonate

P:

phosphate

PP:

diphosphate

TPP:

thiamin diphosphate

References

  • Adam K P and Zapp J 1998 Biosynthesis of the isoprene units of chamomile sesquiterpenes;Phytochemistry 48 953–959

    Article  CAS  Google Scholar 

  • Adam K P, Thiel R and Zapp J 1999 Incorporation of [1-13C] 1-deoxy-D-xylulose in chamomile sesquiterpenes;Arch. Biochem. Biophys. 369 127–132

    Article  CAS  Google Scholar 

  • Adam P, Hecht S, Eisenreich W, Kaiser J, Grawert T, Arigoni D, Bacher A and Rohdich F 2002 Biosynthesis of terpenes: Studies on 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase;Proc. Natl. Acad. Sci. USA 99 12108–12113

    Article  CAS  Google Scholar 

  • Araki N, Kusumi K, Masamoto K, Niwa Y and Iba K 2000 Temperature-sensitive Arabidopsis mutant defective in 1-deoxy-D-xylulose 5-phosphate synthase within the plastid non-mevalonate pathway of isoprenoid biosynthesis;Physiol. Plant. 108 19–24

    CAS  Google Scholar 

  • Arigoni D, Sagner S, Latzel C, Eisenreich W, Bacher A and Zenk M H 1997 Terpenoid biosynthesis from 1-deoxy-Dxylulose in higher plants by intramolecular skeletal rearrangement;Proc. Natl. Acad. Sci. USA 94 10600–10605

    Article  CAS  Google Scholar 

  • Arigoni D, Eisenreich W, Latzel C, Sagner S, Radykewicz T, Zenk M H and Bacher A 1999 Dimethylallyl pyrophosphate is not the committed precursor of isopentenyl pyrophosphate during terpenoid biosynthesis from 1-deoxyxylulose in higher plants;Proc. Natl. Acad. Sci. USA 96 1309–1314

    Article  CAS  Google Scholar 

  • Bach T J 1995 Some aspects of isoprenoid biosynthesis in plants? a review;Lipids 30 191–202

    Article  CAS  Google Scholar 

  • Bouvier F, d’Harlingue A, Suire C, Backhaus R A and Camara B 1998 Dedicated roles of plastid transketolase during the early onset of isoprenoid biogenesis in pepper fruits;Plant Physiol. 117 1423–1431

    Article  CAS  Google Scholar 

  • Carretero-Paulet L, Ahumada I, Cunillera N, Rodriguez-Concepcion M, Ferrer A, Boronat A and Campos N 2002 Expression and molecular analysis of theArabidopsis DXR gene encoding 1-Deoxy-D-xylulose-5-phosphate reductoisomerase, the first committed enzyme of the 2-C-Methyl-Derythritol-4-phosphate pathway;Plant Physiol. 129 1581–1591

    Article  CAS  Google Scholar 

  • Chahed K, Oudin A, Guivarc’h N, Hamdi S, Chenieux J-H, Rideau M and Clastre M 2000 1-Deoxy-D-xylulose-5-phosphate synthase from periwinkle: cDNA identification and induced gene expression in terpenoid indole alkaloidproducing cells;Plant Physiol. Biochem. 38 559–566

    Article  CAS  Google Scholar 

  • Chappell J 1995 Biochemistry and molecular biology of the isoprenoid biosynthetic pathway in plants;Annu. Rev. Plant Physiol. Plant Mol. Biol. 46 521–547

    Article  CAS  Google Scholar 

  • Chappell J, Wolf F, Proulx J, Cuellar R and Saunders C 1995 Is the reaction catalyzed by 3-hydroxy-3-methylglutarylcoenzyme A reductase a rate limiting step for isoprenoid biosynthesis in plants?;Plant Physiol. 109 1337–1343

    Article  CAS  Google Scholar 

  • Contin A, Vander-Heijden R, Lefeber A W M and Verpoorte R 1998 The iridoid glucoside secologanin is derived from the novel triose-phosphate/pyruvate pathway inCatharanthus roseus cell culture;FEBS Lett. 434 413–416

    Article  CAS  Google Scholar 

  • Croteau R 1987 Biosynthesis and catabolism of monoterpenoids;Chem. Rev. 87 929–954

    Article  CAS  Google Scholar 

  • Cunningham F X Jr, Lafond T P and Gantt E 2000 Evidence of a role for LytB in the nonmevalonate pathway of isoprenoid biosynthesis;J. Bacteriol. 182 5841–5848

    Article  CAS  Google Scholar 

  • Dewick P M 2002 The biosynthesis of C5-C25 terpenoid compounds;Nat. Prod. Rep. 19 181–222

    Article  CAS  Google Scholar 

  • Dubey V S 1999Metabolism of monoterpenoids in palmarosa (Cymbopogon martini, Roxb. Vats. Var. motia) inflorescence, Ph.D. thesis, University of Lucknow, Lucknow

    Google Scholar 

  • Eichinger D, Bacher A, Zenk M H and Eisenreich W 1999 Analysis of metabolic pathways via quantitative prediction of isotope labeling patterns: a retrobiosynthetic13C NMR study on the monoterpene loganin;Phytochemistry 51 223–236

    Article  CAS  Google Scholar 

  • Eisenreich W, Menhard B, Hylands P J, Zenk M H and Bacher A 1996 Studies on the biosynthesis of taxol: The taxane carbon skeleton is not of mevalonoid origin;Proc. Natl. Acad. Sci. USA 93 6431–6436

    Article  CAS  Google Scholar 

  • Eisenreich W, Sagner S, Zenk M H and Bacher A 1997 Monoterpenoid essential oils are not of mevalonoid origin;Tetrahedron Lett. 38 3889–3892

    Article  CAS  Google Scholar 

  • Eisenreich W, Rohdich F and Bacher A 2001 Deoxyxylulose phosphate pathway to terpenoids;Trends Plant Sci. 6 78–84

    Article  CAS  Google Scholar 

  • Estévez J M, Cantero A, Romero C, Kawaide H, Jimenez L F, Kuzuyama T, Seto H, Kamiya Y and Leon P 2000 Analysis of the expression ofCLA1, a gene that encodes the 1-deoxy-xylulose 5-phosphate synthase of the 2-C-methyl-D-erythritol-4-phosphate pathway inArabidopsis;Plant Physiol. 124 95–103

    Article  Google Scholar 

  • Estévez J M, Cantero A, Reindl A, Reichler S and León P 2001 1-Deoxy-D-xylulose-5-phosphate Synthase, a Limiting Enzyme for Plastidic Isoprenoid Biosynthesis in Plants;J. Biol. Chem. 276 22901–22909

    Article  Google Scholar 

  • Fellermeier M A, Maier U H, Sagner S, Bacher A and Zenk M H 1998 (-)-2-C-methyl-D-erythrono-1, 4-lactone is formed after application of the terpenoid precursor 1-deoxy-D-xylulose;FEBS Lett. 437 278–280

    Article  CAS  Google Scholar 

  • Fellermeier M, Kis K, Sagner S, Maier U, Bacher A and Zenk M H 1999 Cell-free conversion of 1-deoxy-D-xylulose 5-phosphate and 2-C-methyl-D-erythritol 4-phosphate into β-carotene in higher plants and its inhibition by fosmidomycin;Tetrahedron Lett. 40 2743–2746

    Article  CAS  Google Scholar 

  • Fellermeier M, Raschke M, Sagner S, Wungsintaweekul J, Schuhr C A, Hecht S, Kis K, Radykewicz T, Adam P, Rohdich F, Eisenreich W, Bacher A, Arigoni D and Zenk M H 2001 Studies on the nonmevalonate pathway of terpene biosynthesis. The role of 2C-methyl-D-erythritol 2, 4-cyclodiphosphate in plants;Eur. J. Biochem. 268 6302–6310

    Article  CAS  Google Scholar 

  • Fowler D J, Hamilton J T G, Humphrey A J and O’Hagan D 1999 Plant Terpene Biosynthesis. The Biosynthesis of Linalyl Acetate inMentha citrata;Tetrahedron Lett. 40 3803–3806

    Article  CAS  Google Scholar 

  • Hecht S, Eisenreich W, Adam P, Amslinger S, Kis K, Bacher A, Arigoni D and Rohdich F 2001 Studies on the nonmevalonate pathway to terpenes: the role of the GcpE (IspG) protein;Proc. Natl. Acad. Sci. USA 98 14837–14842

    Article  CAS  Google Scholar 

  • Herz S, Wungsintaweekul J, Schuhr C A, Hecht S, Luttgen H, Sagner S, Fellermeier M, Eisenreich W, Zenk M H, Bacher A and Rohdich F 2000 Biosynthesis of terpenoids: YgbB protein converts 4-diphosphocytidyl-2C-methyl-D-erythritol2-phosphate to 2C-methyl-D-erythritol2, 4-cyclodiphosphate;Proc. Natl. Acad. Sci. USA 97 2486–2490

    Article  CAS  Google Scholar 

  • Hirai N, Yoshida R, Todoroki Y and Ohigashi H 2000 Biosynthesis of abscisic acid by the non-mevalonate pathway in plants, and by the mevalonate pathway in fungi;Biosci. Biotechnol. Biochem. 64 1448–1458

    Article  CAS  Google Scholar 

  • Itoh D, Karunagoda R P, Fushie T, Katoh K and Nabeta K 2000 Nonequivalent labeling of the phytyl side chain of chlorophyll a in callus of the hornwortAnthoceros punctatus;J. Nat. Prod. 63 1090–1093

    Article  CAS  Google Scholar 

  • Julliard J H 1992 Biosynthesis of the pyridoxal ring (vitamin B6) in higher plant chloroplasts and its relationship with the biosynthesis of the thiazole ring (vitamin B1);CR. Acad. Sci. Ser. III 314 285–290

    CAS  Google Scholar 

  • Julliard J H and Douce R 1991 Biosynthesis of the thiazole moiety of thiamin (vitamin B1) in higher plant chloroplasts;Proc. Natl. Acad. Sci. USA 88 2042–2045

    Article  CAS  Google Scholar 

  • Knoss W, Reuter B and Zapp J 1997 Biosynthesis of the labdane diterpenoid marrubin inMarrubium vulgare via a non-mevalonate pathway;Biochem. J. 326 449–454

    Article  CAS  Google Scholar 

  • Lalitha R and Ramasarma T 1987 Role of mevalonate metabolizing enzymes in the biosynthesis of isoprenoid compounds in plants;J. Sci. Ind. Res. 46 386–404

    CAS  Google Scholar 

  • Lange B M, Wildung M R, McCaskill D and Croteau R 1998 A family of transketolases that directs isoprenoid biosynthesis via a mevalonate independent pathway;Proc. Natl. Acad. Sci. USA 95 2100–2104

    Article  CAS  Google Scholar 

  • Lange B M and Croteau R 1999a Isoprenoid biosynthesis via a mevalonate-independent pathway in plants: cloning and heterologous expression of 1-deoxy-D-xylulose-5-phosphate reductoisomerase from peppermint;Arch. Biochem. Biophys. 365 170–174

    Article  CAS  Google Scholar 

  • Lange B M and Croteau R 1999 Isopentenyl diphosphate biosynthesis via a mevalonate-independent pathway: isopentenyl monophosphate kinase catalyses the terminal enzymatic step;Proc. Natl. Acad. Sci. USA 96 13714–13719

    Article  CAS  Google Scholar 

  • Lichtenthaler H K, Schwender J, Disch A and Rohmer M 1997 Biosynthesis of isoprenoids in higher plant chloroplasts proceedsvia a mevalonate-independent pathway;FEBS Lett. 400 271–274

    Article  CAS  Google Scholar 

  • Lichtenthaler H K 1999 The 1-deoxy-D-xylulose-5-phosphate pathway of isoprenoid biosynthesis in plants;Annu. Rev. Plant Physiol. Plant Mol. Biol. 50 47–65

    Article  CAS  Google Scholar 

  • Lichtenthaler H K 2000 Non-mevalonate isoprenoid biosynthesis: enzymes, genes and inhibitors;Biochem. Soc. Trans. 28 785–789

    Article  CAS  Google Scholar 

  • Lichtenthaler H K, Zeidler J, Schwender J and Muller C 2000 The non-mevalonate isoprenoid biosynthesis of plants as a test system for new herbicides and drugs against pathogenic bacteria and the malaria parasite;Z. Naturforsch. 55 305–313

    Article  CAS  Google Scholar 

  • Lois L M, Rodriguez-Concepcion M, Gallego F, Campos N and Boronat A 2000 Carotenoid biosynthesis during tomato fruit development: regulatory role of 1-deoxy-D-xylulose-5-phosphate synthase;Plant J. 22 503–513

    Article  CAS  Google Scholar 

  • Luan F and Wüst M 2002 Differential incorporation of 1-deoxy-d-xylulose into (3S)-linalool and geraniol in grape berry exocarp and mesocarp;Phytochemistry 60 451–459

    Article  CAS  Google Scholar 

  • Luthra R, Dubey V S and Kumar S 1999a Is 3-hydroxy-3-methylglutaryl coenzyme A reductase the key regulatory enzyme in isoprenoid biosynthesis in higher plants?;J. Med. Arom. Plant Sci. 21 647–649

    CAS  Google Scholar 

  • Luthra R, Luthra P M and Kumar S 1999b Redefined role of mevalonate-isoprenoid pathway in terpenoid biosynthesis in higher plants;Curr. Sci. 76 133–135

    CAS  Google Scholar 

  • Luttgen H, Rohdich F, Herz S, Wungsintaweekul J, Hecht S, Schuhr C A, Fellermeier M, Sagner S, Zenk M H, Bacher A and Eisenreich W 2000 Biosynthesis of terpenoids: YchB protein ofEscherichia coli phosphorylates the 2-hydroxy group of 4-diphosphocytidyl-2 C-methyl-D-erythritol;Proc. Natl. Acad. Sci. USA 97 1062–1067

    Article  CAS  Google Scholar 

  • Mahmoud S S and Croteau R 2001 Metabolic engineering of essential oil yield and composition in mint by altering expression of deoxyxylulose phosphate reductoisomerase and menthofuran synthase;Proc. Natl. Acad. Sci. USA 98 8915–8920

    Article  CAS  Google Scholar 

  • Mahmoud S S and Croteau R 2002 Strategies for transgenic manipulation of monoterpene biosynthesis in plants;Trends Plant Sci. 7 366–373

    Article  CAS  Google Scholar 

  • Maier W, Schneider B and Strack D 1998 Biosynthesis of sesquiterpenoid cyclohexane derivatives in mycorrhizal barley roots proceeds via the glyceraldehydes-3-phosphate/pyruvate pathway;Tetrahedron Lett. 39 521–524

    Article  CAS  Google Scholar 

  • McCaskill D and Croteau R 1998 Some caveats for bioengineering terpenoid metabolism in plants;Trends Biotechnol. 16 349–355

    Article  CAS  Google Scholar 

  • McCaskill D and Croteau R 1999 Isopentenyl diphosphate is the terminal product of the deoxyxylulose-5-phosphate pathway for terpenoid biosynthesis in plants;Tetrahedron Lett. 40 653–656

    Article  CAS  Google Scholar 

  • McGarvey D J and Croteau R 1995 Terpenoid metabolism;Plant Cell 7 1015–1026

    Article  CAS  Google Scholar 

  • Milborrow B V and Lee H S 1998 Endogenous biosynthetic precursors of (+) abscisic acid. VI. Carotenoids and abscisic acid formed by the non-mevalonate triose-pyruvate pathway in chloroplasts;Aust. J. Plant Physiol. 25 507–512

    CAS  Google Scholar 

  • Nabeta K, Kawae T, Kikuchi T, Saitoh T and Okuyama H 1995 Biosynthesis of chlorophyll a from 13C-labelled mevalonate and glycine in liverwort: nonequivalent labeling of phytyl side chain;J. Chem. Soc. Chem. Commun. 2529–2530

  • Okada K, Kawaide H, Kuzuyama T, Seto H, Curtis I S and Kamiya Y 2002 Antisense and chemical suppression of the nonmevalonate pathway affects ent-kaurene biosynthesis inArabidopsis;Planta 215 339–344

    Article  CAS  Google Scholar 

  • Rieder C H, Jaun B and Arigoni D 2000 On the early steps of cineol biosynthesis inEucalyptus globules;Helv. Chim. Acta 83 2504–2513

    Article  CAS  Google Scholar 

  • Rodriguez-Concepcion M, Ahumada I, Diez-Juez E, Sauret-Gueto S, Lois L M, Gallego F, Carretero-Paulet L, Campos N, Boronat A 2001 1-Deoxy-D-xylulose 5-phosphate reductoisomerase and plastid isoprenoid biosynthesis during tomato fruit ripening;Plant J. 27 213–222

    Article  CAS  Google Scholar 

  • Rodwell V W, Beach M J, Bischoff K M, Bochar D A, Darnay B G, Friesen J A, Gill J F, Hedl M, Jordan-Starck T, Kennelly P J, Kim D Y and Wang Y 2000 3-Hydroxy-3-methylglutaryl-CoA reductase;Methods Enzymol. 324 259–280

    Article  CAS  Google Scholar 

  • Rohdich F, Wungsintaweekul J, Eisenreich W, Richter G, Schuhr C A, Hecht S, Zenk M H and Bacher A 2000a Biosynthesis of terpenoids: 4-diphosphocytidyl-2C-methyl-D-erythritol synthase ofArabidopsis thaliana;Proc. Natl. Acad. Sci. USA 97 6451–6456

    Article  CAS  Google Scholar 

  • Rohdich F, Wungsintaweekul J, Luttgen H, Fischer M, Eisenreich W, Schuhr C A, Fellermeier M, Schramek N, Zenk M H and Bacher A 2000b Biosynthesis of terpenoids: 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase from tomato;Proc. Natl. Acad. Sci. USA 97 8251–8256

    Article  CAS  Google Scholar 

  • Rohdich F, Kis K, Bacher A and Eisenreich W 2001 The non-mevalonate pathway of isoprenoids: genes, enzymes and intermediates;Curr. Opin. Chem. Biol. 5 535–540

    Article  CAS  Google Scholar 

  • Rohmer M 1999 The discovery of a mevalonate independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants;Nat. Prod. Rep. 16 565–574

    Article  CAS  Google Scholar 

  • Sacchettini J C and Poulter C D 1997 Creating isoprenoid diversity;Science 277 1788–1789

    Article  CAS  Google Scholar 

  • Sagner S, Eisenreich W, Fellermeier M, Latzel C, Bacher A and Zenk M H 1998 Biosynthesis of 2-C-methyl-D-erythritol in plants by rearrangement of the terpenoid precursor, 1-deoxy-D-xylulose-5-phosphate;Tetrahedron Lett. 39 2091–2094

    Article  CAS  Google Scholar 

  • Schwarz K M 1994Terpen-bio synthese in Ginkgo biloba: Eine Uberraschende geschichte, Ph.D. thesis, Eidgenossischen Technischen Hochschule, Zurich, Switzerland

    Google Scholar 

  • Schwender J, Muller C, Zeidler J and Lichtenthaler H K 1999 Cloning and heterologous expression of a cDNA encoding 1-deoxy-D-xylulose-5-phosphate reductoisomerase ofArabidopsis thaliana;FEBS Lett. 455 140–144

    Article  CAS  Google Scholar 

  • Singh N, Luthra R, Sangwan R S and Thakur R S 1989 Metabolism of monoterpenoids in aromatic plants;Curr. Res. Med. Arom. Plants 11 174–197

    Google Scholar 

  • Thiel R and Adam K P 2002 Incorporation of [1-13C]1-deoxy-d-xylulose into isoprenoids of the liverwortConocephalum conicum;Phytochemistry 59 269–274

    Article  CAS  Google Scholar 

  • Veau B, Courtois M, Oudin A, Chenieux J C, Rideau M and Clastre M 2000 Cloning and expression of cDNAs encoding two enzymes of the MEP pathway inCatharanthus roseus;Biochim. Biophys. Acta 1517 159–163

    Article  CAS  Google Scholar 

  • Walter M H, Fester T and Strack D 2000 Arbuscular mycorrhizal fungi induce the non-mevalonate methylerythritol phosphate pathway of isoprenoid biosynthesis correlated with accumulation of the ‘yellow pigment’ and other apocarotenoids;Plant J. 21 571–578

    Article  CAS  Google Scholar 

  • Walter M H, Hans J and Strack D 2002 Two distantly related genes encoding 1-deoxy-D-xylulose 5-phosphate synthases: differential regulation in shoots and apocarotenoid-accumulating mycorrhizal roots;Plant J. 31 243–254

    Article  CAS  Google Scholar 

  • Zeidler J G, Lichtenthaler H K, May H U and Lichtenthaler F W 1997 Is isoprene emitted by plants synthesized via a novel isopentenyl pyrophosphate pathway?;Z. Naturforsch. 52C 15–23

    Article  Google Scholar 

  • Zeidler J G, Schwender J, Muller C, Wiesner J, Weidemeyer C, Beck E, Jomaa H and Lichtenthaler H K 1998 Inhibition of the non-mevalonate 1-deoxy-D-xylulose-5-phosphate pathway of plant isoprenoid biosynthesis by fosmidomycin;Z. Naturforsch. 53C 980–986

    Article  Google Scholar 

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Dubey, V.S., Bhalla, R. & Luthra, R. An overview of the non-mevalonate pathway for terpenoid biosynthesis in plants. J. Biosci. 28, 637–646 (2003). https://doi.org/10.1007/BF02703339

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