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MetaCyc Pathway: trans, trans-farnesyl diphosphate biosynthesis
Inferred from experiment

Enzyme View:

Pathway diagram: trans, trans-farnesyl diphosphate biosynthesis

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: FPP biosynthesis, trans, trans-farnesyl diphosphate biosynthesis

Superclasses: BiosynthesisCofactors, Prosthetic Groups, Electron Carriers BiosynthesisPolyprenyl BiosynthesisAll-Trans-Farnesyl-PP-Biosynthesis

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Escherichia coli K-12 substr. MG1655, Ginkgo biloba, Homo sapiens, Methanothermobacter marburgensis Marburg, Saccharomyces cerevisiae

Expected Taxonomic Range: Archaea, Bacteria , Eukaryota

General Background

(2E,6E)-farnesyl diphosphate (farnesyl pyrophosphate, FPP) is a crucial compound involved in the biosynthesis of a variety of terpenoids including sesquiterpenoids and sterols. Moreover, FPP is also used in posttranslational modifications of proteins (farnesylation) which is believed to act as a membrane attachment device.

The biosynthesis of FPP is largely thought to occur in the cytosol where sesquiterpenoids and sterols are produced. This cytosolic FPP is synthesized from the condensation of dimethylallyl diphosphate (dimethylallyl pyrophosphate, DMAPP) and two molecules of isopentenyl diphosphate (isopentenyl pyrophosphate, IPP) originating from the mevalonate pathway I [Kappers05, Wallaart01]. In plants FPP is found not only in the cytosol, but also in plastids and mitochondria [Aharoni03, Kappers05]) where IPP and DMAPP may originate from the methylerythritol phosphate pathway I instead of the mevalonate pathway.

The synthesis of FPP is the result of two head-to-tail condensation reactions: first geranyl diphosphate (geranyl pyrophosphate, GPP) is formed from the condensation of DMAPP and IPP; then another IPP molecule is added to form FPP.

Superpathways: superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate), superpathway of geranylgeranyl diphosphate biosynthesis II (via MEP), taxadiene biosynthesis (engineered), polyisoprenoid biosynthesis (E. coli), superpathway of ergosterol biosynthesis II, superpathway of cholesterol biosynthesis, superpathway of ergosterol biosynthesis I, Methanobacterium thermoautotrophicum biosynthetic metabolism

Variants: farnesylcysteine salvage pathway

Unification Links: AraCyc:PWY-5123, EcoCyc:PWY-5123

Created 27-Feb-2006 by Tissier C, TAIR


Aharoni03: Aharoni A, Giri AP, Deuerlein S, Griepink F, de Kogel WJ, Verstappen FW, Verhoeven HA, Jongsma MA, Schwab W, Bouwmeester HJ (2003). "Terpenoid metabolism in wild-type and transgenic Arabidopsis plants." Plant Cell 15(12);2866-84. PMID: 14630967

Cunillera96: Cunillera N, Arro M, Delourme D, Karst F, Boronat A, Ferrer A (1996). "Arabidopsis thaliana contains two differentially expressed farnesyl-diphosphate synthase genes." J Biol Chem 271(13);7774-80. PMID: 8631820

Delourme94: Delourme D, Lacroute F, Karst F (1994). "Cloning of an Arabidopsis thaliana cDNA coding for farnesyl diphosphate synthase by functional complementation in yeast." Plant Mol Biol 26(6);1867-73. PMID: 7858223

Kappers05: Kappers IF, Aharoni A, van Herpen TW, Luckerhoff LL, Dicke M, Bouwmeester HJ (2005). "Genetic engineering of terpenoid metabolism attracts bodyguards to Arabidopsis." Science 309(5743);2070-2. PMID: 16179482

Wallaart01: Wallaart TE, Bouwmeester HJ, Hille J, Poppinga L, Maijers NC (2001). "Amorpha-4,11-diene synthase: cloning and functional expression of a key enzyme in the biosynthetic pathway of the novel antimalarial drug artemisinin." Planta 212(3);460-5. PMID: 11289612

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Anderson89: Anderson MS, Muehlbacher M, Street IP, Proffitt J, Poulter CD (1989). "Isopentenyl diphosphate:dimethylallyl diphosphate isomerase. An improved purification of the enzyme and isolation of the gene from Saccharomyces cerevisiae." J Biol Chem 1989;264(32);19169-75. PMID: 2681212

Anderson89a: Anderson MS, Yarger JG, Burck CL, Poulter CD (1989). "Farnesyl diphosphate synthetase. Molecular cloning, sequence, and expression of an essential gene from Saccharomyces cerevisiae." J Biol Chem 1989;264(32);19176-84. PMID: 2681213

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Barnard81: Barnard GF, Popjak G (1981). "Human liver prenyltransferase and its characterization." Biochim Biophys Acta 661(1);87-99. PMID: 7295734

Blanchard93: Blanchard L, Karst F (1993). "Characterization of a lysine-to-glutamic acid mutation in a conservative sequence of farnesyl diphosphate synthase from Saccharomyces cerevisiae." Gene 125(2);185-9. PMID: 8096487

Bonanno01: Bonanno JB, Edo C, Eswar N, Pieper U, Romanowski MJ, Ilyin V, Gerchman SE, Kycia H, Studier FW, Sali A, Burley SK (2001). "Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis." Proc Natl Acad Sci U S A 98(23);12896-901. PMID: 11698677

Bouvier00: Bouvier F, Suire C, d'Harlingue A, Backhaus RA, Camara B (2000). "Molecular cloning of geranyl diphosphate synthase and compartmentation of monoterpene synthesis in plant cells." Plant J 24(2);241-52. PMID: 11069698

Breitling03: Breitling R, Laubner D, Clizbe D, Adamski J, Krisans SK (2003). "Isopentenyl-diphosphate isomerases in human and mouse: evolutionary analysis of a mammalian gene duplication." J Mol Evol 57(3);282-91. PMID: 14629038

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Burke02: Burke C, Croteau R (2002). "Interaction with the small subunit of geranyl diphosphate synthase modifies the chain length specificity of geranylgeranyl diphosphate synthase to produce geranyl diphosphate." J Biol Chem 277(5);3141-9. PMID: 11733504

Burke04: Burke C, Klettke K, Croteau R (2004). "Heteromeric geranyl diphosphate synthase from mint: construction of a functional fusion protein and inhibition by bisphosphonate substrate analogs." Arch Biochem Biophys 422(1);52-60. PMID: 14725857

Burke99: Burke CC, Wildung MR, Croteau R (1999). "Geranyl diphosphate synthase: cloning, expression, and characterization of this prenyltransferase as a heterodimer." Proc Natl Acad Sci U S A 96(23);13062-7. PMID: 10557273

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

Campbell98: Campbell M, Hahn FM, Poulter CD, Leustek T (1998). "Analysis of the isopentenyl diphosphate isomerase gene family from Arabidopsis thaliana." Plant Mol Biol 36(2);323-8. PMID: 9484444

Carrigan03: Carrigan CN, Poulter CD (2003). "Zinc is an essential cofactor for type I isopentenyl diphosphate:dimethylallyl diphosphate isomerase." J Am Chem Soc 125(30);9008-9. PMID: 15369345

Chen08: Chen CKM, Hudock MP, Zhang Y, Guo RT, Cao R, No JH, Liang PH, Ko TP, Chang TH, Chang SC, Song Y, Axelson J, Kumar A, Wang AH, Oldfield E (2008). "Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation." J Med Chem 51(18);5594-607. PMID: 18800762

Chen93: Chen A, Poulter CD (1993). "Purification and characterization of farnesyl diphosphate/geranylgeranyl diphosphate synthase. A thermostable bifunctional enzyme from Methanobacterium thermoautotrophicum." J Biol Chem 268(15);11002-7. PMID: 8388380

Chen94a: Chen A, Poulter CD (1994). "Isolation and characterization of idsA: the gene for the short chain isoprenyl diphosphate synthase from Methanobacterium thermoautotrophicum." Arch Biochem Biophys 314(2);399-404. PMID: 7979381

Chooi10: Chooi YH, Cacho R, Tang Y (2010). "Identification of the viridicatumtoxin and griseofulvin gene clusters from Penicillium aethiopicum." Chem Biol 17(5);483-94. PMID: 20534346

Chooi12: Chooi YH, Fang J, Li Y, Wu K, Wang P, Tang Y (2012). "Discovery and characterization of a group of fungal polycyclic polyketide prenyltransferases." J Am Chem Soc 134(22);9428-37. PMID: 22590971

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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