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Pathway Description
MEP/DOXP Pathway
Arabidopsis thaliana
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2019-05-08
Last Updated: 2019-08-14
The DOXP/MEP pathway, also known as the non-mevalonate pathway, plays an essential role in creating the chemicals needed for many plants to function. This pathway, combined with the MEP/DOXP pathway give many plants their scents, such as cinnamon and ginger, and are responsible for the red colour in tomatoes. Terpenoids, also called isoprenoids, are a substantial yet varied class of organic chemicals that occur naturally. Plant terpenoids have aromatic qualities and are used for this and their role in traditional herbal remedies. The pathway begins with D-glyceraldehyde 3-phosphate, which is produced through glycolysis. Together with pyruvic acid and the enzyme 1-deoxy-D-xylulose 5-phosphate synthase 1, these are catalyzed into 1-deoxy-xylulose 5-phosphate. From there, 1-deoxy-xylulose 5-phosphate teams up with 1-deoxy-D-xylulose 5-phosphate reductoisomerase to create 2-c-methyl-D-erythritol 4-phosphate. Moving along in the chloroplast, after being produced through 2-c-methyl-D-erythritol 4-phosphate and the enzyme 2-c-methyl-D-erythritol 4-phosphate cytidyltransferase,4-cytidine 5'-diphospho)-2-C-methyl-D-erythritol is catalyzed by 4-diphosphocytidyl-2-c-methyl-D-erythritol kinase to create 2-phospho-4-(cytidine 5'-diphospho)-2-c-methyl-D-erythritol. After that, 2-c-methyl-D-erythritol 2,4-cyclodiphosphate synthase uses the newly produced 2-phospho-4-(cytidine 5'-diphospho)-2-c-methyl-D-erythritol to create 2-c-methyl-D-erythritol-2,4-cyclodiphosphate. This compound is then joined with 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase to become 1-hydroxy-2-methyl-2-butenyl 4-diphosphate. This compound gets busy soon after its inception, branching off into two separate reactions: first reacting with 4-hydroxy-3-methylbut-2-enyl diphosphate reductase to create isopentenyl pyrophosphate, then reacting with the same enzyme to create dimethylallylpyrophosphate. Dimethylallylpyrophosphate is then looped into another reaction with isopentenyl-diphosphate delta-isomerase II, recreating isopentenyl pyrophosphate. It also reacts with geranylgeranyl pyrophosphate synthase 6, bringing the pathway into the mitochondrion to create geranyl pyrophosphate. This is later followed by a monoterpenoid biosynthesis pathway.
References
MEP/DOXP Pathway References
Wanke M, Skorupinska-Tudek K, Swiezewska E: Isoprenoid biosynthesis via 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate (DOXP/MEP) pathway. Acta Biochim Pol. 2001;48(3):663-72.
Pubmed: 11833775
Hunter, W. (2007). The Non-mevalonate Pathway of Isoprenoid Precursor Biosynthesis. Journal Of Biological Chemistry, 282(30), 21573-21577. doi: 10.1074/jbc.r700005200
Salanoubat M, Lemcke K, Rieger M, Ansorge W, Unseld M, Fartmann B, Valle G, Blocker H, Perez-Alonso M, Obermaier B, Delseny M, Boutry M, Grivell LA, Mache R, Puigdomenech P, De Simone V, Choisne N, Artiguenave F, Robert C, Brottier P, Wincker P, Cattolico L, Weissenbach J, Saurin W, Quetier F, Schafer M, Muller-Auer S, Gabel C, Fuchs M, Benes V, Wurmbach E, Drzonek H, Erfle H, Jordan N, Bangert S, Wiedelmann R, Kranz H, Voss H, Holland R, Brandt P, Nyakatura G, Vezzi A, D'Angelo M, Pallavicini A, Toppo S, Simionati B, Conrad A, Hornischer K, Kauer G, Lohnert TH, Nordsiek G, Reichelt J, Scharfe M, Schon O, Bargues M, Terol J, Climent J, Navarro P, Collado C, Perez-Perez A, Ottenwalder B, Duchemin D, Cooke R, Laudie M, Berger-Llauro C, Purnelle B, Masuy D, de Haan M, Maarse AC, Alcaraz JP, Cottet A, Casacuberta E, Monfort A, Argiriou A, flores M, Liguori R, Vitale D, Mannhaupt G, Haase D, Schoof H, Rudd S, Zaccaria P, Mewes HW, Mayer KF, Kaul S, Town CD, Koo HL, Tallon LJ, Jenkins J, Rooney T, Rizzo M, Walts A, Utterback T, Fujii CY, Shea TP, Creasy TH, Haas B, Maiti R, Wu D, Peterson J, Van Aken S, Pai G, Militscher J, Sellers P, Gill JE, Feldblyum TV, Preuss D, Lin X, Nierman WC, Salzberg SL, White O, Venter JC, Fraser CM, Kaneko T, Nakamura Y, Sato S, Kato T, Asamizu E, Sasamoto S, Kimura T, Idesawa K, Kawashima K, Kishida Y, Kiyokawa C, Kohara M, Matsumoto M, Matsuno A, Muraki A, Nakayama S, Nakazaki N, Shinpo S, Takeuchi C, Wada T, Watanabe A, Yamada M, Yasuda M, Tabata S: Sequence and analysis of chromosome 3 of the plant Arabidopsis thaliana. Nature. 2000 Dec 14;408(6814):820-2. doi: 10.1038/35048706.
Pubmed: 11130713
Cheng CY, Krishnakumar V, Chan AP, Thibaud-Nissen F, Schobel S, Town CD: Araport11: a complete reannotation of the Arabidopsis thaliana reference genome. Plant J. 2017 Feb;89(4):789-804. doi: 10.1111/tpj.13415. Epub 2017 Feb 10.
Pubmed: 27862469
Carretero-Paulet L, Ahumada I, Cunillera N, Rodriguez-Concepcion M, Ferrer A, Boronat A, Campos N: Expression and molecular analysis of the Arabidopsis DXR gene encoding 1-deoxy-D-xylulose 5-phosphate reductoisomerase, the first committed enzyme of the 2-C-methyl-D-erythritol 4-phosphate pathway. Plant Physiol. 2002 Aug;129(4):1581-91. doi: 10.1104/pp.003798.
Pubmed: 12177470
Sato S, Kaneko T, Kotani H, Nakamura Y, Asamizu E, Miyajima N, Tabata S: Structural analysis of Arabidopsis thaliana chromosome 5. IV. Sequence features of the regions of 1,456,315 bp covered by nineteen physically assigned P1 and TAC clones. DNA Res. 1998 Feb 28;5(1):41-54. doi: 10.1093/dnares/5.1.41.
Pubmed: 9628582
Rohdich F, Wungsintaweekul J, Eisenreich W, Richter G, Schuhr CA, Hecht S, Zenk MH, Bacher A: Biosynthesis of terpenoids: 4-diphosphocytidyl-2C-methyl-D-erythritol synthase of Arabidopsis thaliana. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6451-6. doi: 10.1073/pnas.97.12.6451.
Pubmed: 10841550
Okada K, Kawaide H, Kuzuyama T, Seto H, Curtis IS, Kamiya Y: Antisense and chemical suppression of the nonmevalonate pathway affects ent-kaurene biosynthesis in Arabidopsis. Planta. 2002 Jun;215(2):339-44. doi: 10.1007/s00425-002-0762-0. Epub 2002 Apr 12.
Pubmed: 12029484
Lin X, Kaul S, Rounsley S, Shea TP, Benito MI, Town CD, Fujii CY, Mason T, Bowman CL, Barnstead M, Feldblyum TV, Buell CR, Ketchum KA, Lee J, Ronning CM, Koo HL, Moffat KS, Cronin LA, Shen M, Pai G, Van Aken S, Umayam L, Tallon LJ, Gill JE, Adams MD, Carrera AJ, Creasy TH, Goodman HM, Somerville CR, Copenhaver GP, Preuss D, Nierman WC, White O, Eisen JA, Salzberg SL, Fraser CM, Venter JC: Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana. Nature. 1999 Dec 16;402(6763):761-8. doi: 10.1038/45471.
Pubmed: 10617197
Yamada K, Lim J, Dale JM, Chen H, Shinn P, Palm CJ, Southwick AM, Wu HC, Kim C, Nguyen M, Pham P, Cheuk R, Karlin-Newmann G, Liu SX, Lam B, Sakano H, Wu T, Yu G, Miranda M, Quach HL, Tripp M, Chang CH, Lee JM, Toriumi M, Chan MM, Tang CC, Onodera CS, Deng JM, Akiyama K, Ansari Y, Arakawa T, Banh J, Banno F, Bowser L, Brooks S, Carninci P, Chao Q, Choy N, Enju A, Goldsmith AD, Gurjal M, Hansen NF, Hayashizaki Y, Johnson-Hopson C, Hsuan VW, Iida K, Karnes M, Khan S, Koesema E, Ishida J, Jiang PX, Jones T, Kawai J, Kamiya A, Meyers C, Nakajima M, Narusaka M, Seki M, Sakurai T, Satou M, Tamse R, Vaysberg M, Wallender EK, Wong C, Yamamura Y, Yuan S, Shinozaki K, Davis RW, Theologis A, Ecker JR: Empirical analysis of transcriptional activity in the Arabidopsis genome. Science. 2003 Oct 31;302(5646):842-6. doi: 10.1126/science.1088305.
Pubmed: 14593172
Theologis A, Ecker JR, Palm CJ, Federspiel NA, Kaul S, White O, Alonso J, Altafi H, Araujo R, Bowman CL, Brooks SY, Buehler E, Chan A, Chao Q, Chen H, Cheuk RF, Chin CW, Chung MK, Conn L, Conway AB, Conway AR, Creasy TH, Dewar K, Dunn P, Etgu P, Feldblyum TV, Feng J, Fong B, Fujii CY, Gill JE, Goldsmith AD, Haas B, Hansen NF, Hughes B, Huizar L, Hunter JL, Jenkins J, Johnson-Hopson C, Khan S, Khaykin E, Kim CJ, Koo HL, Kremenetskaia I, Kurtz DB, Kwan A, Lam B, Langin-Hooper S, Lee A, Lee JM, Lenz CA, Li JH, Li Y, Lin X, Liu SX, Liu ZA, Luros JS, Maiti R, Marziali A, Militscher J, Miranda M, Nguyen M, Nierman WC, Osborne BI, Pai G, Peterson J, Pham PK, Rizzo M, Rooney T, Rowley D, Sakano H, Salzberg SL, Schwartz JR, Shinn P, Southwick AM, Sun H, Tallon LJ, Tambunga G, Toriumi MJ, Town CD, Utterback T, Van Aken S, Vaysberg M, Vysotskaia VS, Walker M, Wu D, Yu G, Fraser CM, Venter JC, Davis RW: Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana. Nature. 2000 Dec 14;408(6814):816-20. doi: 10.1038/35048500.
Pubmed: 11130712
Querol J, Campos N, Imperial S, Boronat A, Rodriguez-Concepcion M: Functional analysis of the Arabidopsis thaliana GCPE protein involved in plastid isoprenoid biosynthesis. FEBS Lett. 2002 Mar 13;514(2-3):343-6. doi: 10.1016/s0014-5793(02)02402-x.
Pubmed: 11943178
Sato S, Kotani H, Nakamura Y, Kaneko T, Asamizu E, Fukami M, Miyajima N, Tabata S: Structural analysis of Arabidopsis thaliana chromosome 5. I. Sequence features of the 1.6 Mb regions covered by twenty physically assigned P1 clones. DNA Res. 1997 Jun 30;4(3):215-30. doi: 10.1093/dnares/4.3.215.
Pubmed: 9330910
Guevara-Garcia A, San Roman C, Arroyo A, Cortes ME, de la Luz Gutierrez-Nava M, Leon P: Characterization of the Arabidopsis clb6 mutant illustrates the importance of posttranscriptional regulation of the methyl-D-erythritol 4-phosphate pathway. Plant Cell. 2005 Feb;17(2):628-43. doi: 10.1105/tpc.104.028860. Epub 2005 Jan 19.
Pubmed: 15659625
Hsieh MH, Goodman HM: The Arabidopsis IspH homolog is involved in the plastid nonmevalonate pathway of isoprenoid biosynthesis. Plant Physiol. 2005 Jun;138(2):641-53. doi: 10.1104/pp.104.058735. Epub 2005 Apr 29.
Pubmed: 15863698
Mayer K, Schuller C, Wambutt R, Murphy G, Volckaert G, Pohl T, Dusterhoft A, Stiekema W, Entian KD, Terryn N, Harris B, Ansorge W, Brandt P, Grivell L, Rieger M, Weichselgartner M, de Simone V, Obermaier B, Mache R, Muller M, Kreis M, Delseny M, Puigdomenech P, Watson M, Schmidtheini T, Reichert B, Portatelle D, Perez-Alonso M, Boutry M, Bancroft I, Vos P, Hoheisel J, Zimmermann W, Wedler H, Ridley P, Langham SA, McCullagh B, Bilham L, Robben J, Van der Schueren J, Grymonprez B, Chuang YJ, Vandenbussche F, Braeken M, Weltjens I, Voet M, Bastiaens I, Aert R, Defoor E, Weitzenegger T, Bothe G, Ramsperger U, Hilbert H, Braun M, Holzer E, Brandt A, Peters S, van Staveren M, Dirske W, Mooijman P, Klein Lankhorst R, Rose M, Hauf J, Kotter P, Berneiser S, Hempel S, Feldpausch M, Lamberth S, Van den Daele H, De Keyser A, Buysshaert C, Gielen J, Villarroel R, De Clercq R, Van Montagu M, Rogers J, Cronin A, Quail M, Bray-Allen S, Clark L, Doggett J, Hall S, Kay M, Lennard N, McLay K, Mayes R, Pettett A, Rajandream MA, Lyne M, Benes V, Rechmann S, Borkova D, Blocker H, Scharfe M, Grimm M, Lohnert TH, Dose S, de Haan M, Maarse A, Schafer M, Muller-Auer S, Gabel C, Fuchs M, Fartmann B, Granderath K, Dauner D, Herzl A, Neumann S, Argiriou A, Vitale D, Liguori R, Piravandi E, Massenet O, Quigley F, Clabauld G, Mundlein A, Felber R, Schnabl S, Hiller R, Schmidt W, Lecharny A, Aubourg S, Chefdor F, Cooke R, Berger C, Montfort A, Casacuberta E, Gibbons T, Weber N, Vandenbol M, Bargues M, Terol J, Torres A, Perez-Perez A, Purnelle B, Bent E, Johnson S, Tacon D, Jesse T, Heijnen L, Schwarz S, Scholler P, Heber S, Francs P, Bielke C, Frishman D, Haase D, Lemcke K, Mewes HW, Stocker S, Zaccaria P, Bevan M, Wilson RK, de la Bastide M, Habermann K, Parnell L, Dedhia N, Gnoj L, Schutz K, Huang E, Spiegel L, Sehkon M, Murray J, Sheet P, Cordes M, Abu-Threideh J, Stoneking T, Kalicki J, Graves T, Harmon G, Edwards J, Latreille P, Courtney L, Cloud J, Abbott A, Scott K, Johnson D, Minx P, Bentley D, Fulton B, Miller N, Greco T, Kemp K, Kramer J, Fulton L, Mardis E, Dante M, Pepin K, Hillier L, Nelson J, Spieth J, Ryan E, Andrews S, Geisel C, Layman D, Du H, Ali J, Berghoff A, Jones K, Drone K, Cotton M, Joshu C, Antonoiu B, Zidanic M, Strong C, Sun H, Lamar B, Yordan C, Ma P, Zhong J, Preston R, Vil D, Shekher M, Matero A, Shah R, Swaby IK, O'Shaughnessy A, Rodriguez M, Hoffmann J, Till S, Granat S, Shohdy N, Hasegawa A, Hameed A, Lodhi M, Johnson A, Chen E, Marra M, Martienssen R, McCombie WR: Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana. Nature. 1999 Dec 16;402(6763):769-77. doi: 10.1038/47134.
Pubmed: 10617198
Zhu XF, Suzuki K, Saito T, Okada K, Tanaka K, Nakagawa T, Matsuda H, Kawamukai M: Geranylgeranyl pyrophosphate synthase encoded by the newly isolated gene GGPS6 from Arabidopsis thaliana is localized in mitochondria. Plant Mol Biol. 1997 Oct;35(3):331-41. doi: 10.1023/a:1005898805326.
Pubmed: 9349257
Okada K, Saito T, Nakagawa T, Kawamukai M, Kamiya Y: Five geranylgeranyl diphosphate synthases expressed in different organs are localized into three subcellular compartments in Arabidopsis. Plant Physiol. 2000 Apr;122(4):1045-56. doi: 10.1104/pp.122.4.1045.
Pubmed: 10759500
Campbell M, Hahn FM, Poulter CD, Leustek T: Analysis of the isopentenyl diphosphate isomerase gene family from Arabidopsis thaliana. Plant Mol Biol. 1998 Jan;36(2):323-8. doi: 10.1023/a:1005935516274.
Pubmed: 9484444
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