MetaCyc Pathway: superpathway of geranylgeranyl diphosphate biosynthesis II (via MEP)

Pathway diagram: superpathway of geranylgeranyl diphosphate biosynthesis II (via MEP)

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: GGPP biosynthesis II (plastidic)

Superclasses: BiosynthesisCofactors, Prosthetic Groups, Electron Carriers BiosynthesisPolyprenyl BiosynthesisGeranylgeranyl Diphosphate Biosynthesis
BiosynthesisSecondary Metabolites BiosynthesisTerpenoids BiosynthesisDiterpenoids Biosynthesis

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Capsicum annuum, Chlamydomonas reinhardtii, Escherichia coli K-12 substr. MG1655, Hevea brasiliensis

Expected Taxonomic Range: Bacteria , Viridiplantae

General Background

geranylgeranyl diphosphate (also known as geranylgeranyl pyrophosphate, or GGPP) is a crucial compound involved in the biosynthesis of a variety of terpenes and terpenoids, including central compounds such as ubiquinones and menaquinones.

In plants, geranylgeranyl diphosphate is an intermediate in the biosynthesis of essentail compounds such as chlorophylls, carotenoids, tocopherols, plastoquinones, and gibberellins [RodriguezConcep02], as well as a variety of secondary metabolites.

In addition, GGPP is also used in posttranslational modifications of proteins (geranylgeranylation) which is important for membrane adhesion as well as the function of some proteins [Caldelari01, Johnson05].

GGPP is synthesized from (2E,6E)-farnesyl diphosphate either by dedicated enzymes, such as the farnesyltranstransferase of Saccharomyces cerevisiae, or by the action of polyprenyl transferases such as the solanesyl diphosphate synthase from Rhodobacter capsulatus or octaprenyl diphosphate synthase from Escherichia coli K-12. It should be noted that the building blocks for (2E,6E)-farnesyl diphosphate are synthesized in different organisms by different pathways. While most eukaryotes and some bacteria use the mevalonate pathway I, most bacteria, as well as green algae utilize the methylerythritol phosphate pathway I (as described in the two superpathways superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate) and superpathway of geranylgeranyl diphosphate biosynthesis II (via MEP)).

In plants, GGPP is synthesized using both routes - in the cytosol using the mevalonate pathway I, and in the plastids using the methylerythritol phosphate pathway I.

This superpathway describes the production of GGPP via the methylerythritol phosphate pathway I.

In plants, plastidic GGPP is a central metabolite, involved in the biosythesis of a variety of compounds (see list given above).

Subpathways: methylerythritol phosphate pathway I, trans, trans-farnesyl diphosphate biosynthesis, geranylgeranyl diphosphate biosynthesis

Unification Links: AraCyc:PWY-5121

Created 24-Feb-2006 by Tissier C, TAIR
Revised 01-May-2008 by Caspi R, SRI International


Caldelari01: Caldelari D, Sternberg H, Rodriguez-Concepcion M, Gruissem W, Yalovsky S (2001). "Efficient prenylation by a plant geranylgeranyltransferase-I requires a functional CaaL box motif and a proximal polybasic domain." Plant Physiol 126(4);1416-29. PMID: 11500541

Johnson05: Johnson CD, Chary SN, Chernoff EA, Zeng Q, Running MP, Crowell DN (2005). "Protein geranylgeranyltransferase I is involved in specific aspects of abscisic acid and auxin signaling in Arabidopsis." Plant Physiol 139(2);722-33. PMID: 16183844

RodriguezConcep02: Rodriguez-Concepcion M, Boronat A (2002). "Elucidation of the methylerythritol phosphate pathway for isoprenoid biosynthesis in bacteria and plastids. A metabolic milestone achieved through genomics." Plant Physiol 130(3);1079-89. PMID: 12427975

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

Adam02: Adam P, Hecht S, Eisenreich W, Kaiser J, Grawert T, Arigoni D, Bacher A, Rohdich F (2002). "Biosynthesis of terpenes: studies on 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase." Proc Natl Acad Sci U S A 99(19);12108-13. PMID: 12198182

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

Alper05: Alper H, Fischer C, Nevoigt E, Stephanopoulos G (2005). "Tuning genetic control through promoter engineering." Proc Natl Acad Sci U S A 102(36);12678-83. PMID: 16123130

Altincicek01: Altincicek B, Moll J, Campos N, Foerster G, Beck E, Hoeffler JF, Grosdemange-Billiard C, Rodriguez-Concepcion M, Rohmer M, Boronat A, Eberl M, Jomaa H (2001). "Cutting edge: human gamma delta T cells are activated by intermediates of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis." J Immunol 166(6);3655-8. PMID: 11238603

Altincicek01a: Altincicek B, Kollas A, Eberl M, Wiesner J, Sanderbrand S, Hintz M, Beck E, Jomaa H (2001). "LytB, a novel gene of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli." FEBS Lett 499(1-2);37-40. PMID: 11418107

Altincicek01b: Altincicek B, Kollas AK, Sanderbrand S, Wiesner J, Hintz M, Beck E, Jomaa H (2001). "GcpE is involved in the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli." J Bacteriol 183(8);2411-6. PMID: 11274098

Amslinger02: Amslinger S, Kis K, Hecht S, Adam P, Rohdich F, Arigoni D, Bacher A, Eisenreich W (2002). "Biosynthesis of terpenes. Preparation of (E)-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate, an intermediate of the deoxyxylulose phosphate pathway." J Org Chem 67(13);4590-4. PMID: 12076162

Anderson89: 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

Anderson89a: 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

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

Armstrong15: Armstrong CM, Meyers DJ, Imlay LS, Freel Meyers C, Odom AR (2015). "Resistance to the Antimicrobial Agent Fosmidomycin and an FR900098 Prodrug through Mutations in the Deoxyxylulose Phosphate Reductoisomerase Gene (dxr)." Antimicrob Agents Chemother 59(9);5511-9. PMID: 26124156

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

Badger05: Badger J, Sauder JM, Adams JM, Antonysamy S, Bain K, Bergseid MG, Buchanan SG, Buchanan MD, Batiyenko Y, Christopher JA, Emtage S, Eroshkina A, Feil I, Furlong EB, Gajiwala KS, Gao X, He D, Hendle J, Huber A, Hoda K, Kearins P, Kissinger C, Laubert B, Lewis HA, Lin J, Loomis K, Lorimer D, Louie G, Maletic M, Marsh CD, Miller I, Molinari J, Muller-Dieckmann HJ, Newman JM, Noland BW, Pagarigan B, Park F, Peat TS, Post KW, Radojicic S, Ramos A, Romero R, Rutter ME, Sanderson WE, Schwinn KD, Tresser J, Winhoven J, Wright TA, Wu L, Xu J, Harris TJ (2005). "Structural analysis of a set of proteins resulting from a bacterial genomics project." Proteins 60(4);787-96. PMID: 16021622

Badillo95: Badillo A, Steppuhn J, Deruere J, Camara B, Kuntz M (1995). "Structure of a functional geranylgeranyl pyrophosphate synthase gene from Capsicum annuum." Plant Mol Biol 27(2);425-8. PMID: 7888631

Baker92: Baker J, Franklin DB, Parker J (1992). "Sequence and characterization of the gcpE gene of Escherichia coli." FEMS Microbiol Lett 73(1-2);175-80. PMID: 1521767

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

Bartee15: Bartee D, Morris F, Al-Khouja A, Freel Meyers CL (2015). "Hydroxybenzaldoximes Are D-GAP-Competitive Inhibitors of E. coli 1-Deoxy-D-Xylulose-5-Phosphate Synthase." Chembiochem 16(12);1771-81. PMID: 26174207

Begley99: Begley TP, Downs DM, Ealick SE, McLafferty FW, Van Loon AP, Taylor S, Campobasso N, Chiu HJ, Kinsland C, Reddick JJ, Xi J (1999). "Thiamin biosynthesis in prokaryotes." Arch Microbiol 1999;171(5);293-300. PMID: 10382260

Behnen12: Behnen J, Koster H, Neudert G, Craan T, Heine A, Klebe G (2012). "Experimental and computational active site mapping as a starting point to fragment-based lead discovery." ChemMedChem 7(2);248-61. PMID: 22213702

Bernal05: Bernal C, Palacin C, Boronat A, Imperial S (2005). "A colorimetric assay for the determination of 4-diphosphocytidyl-2-C-methyl-D-erythritol 4-phosphate synthase activity." Anal Biochem 337(1);55-61. PMID: 15649375

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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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