Preferences help
enabled [disable] Abstract
Number of results
2005 | 52 | 1 | 45-55
Article title

Farnesyl diphosphate synthase; regulation of product specificity.

Title variants
Languages of publication
Farnesyl diphosphate synthase (FPPS) is a key enzyme in isoprenoid biosynthesis which supplies sesquiterpene precursors for several classes of essential metabolites including sterols, dolichols, ubiquinones and carotenoids as well as substrates for farnesylation and geranylgeranylation of proteins. It catalyzes the sequential head-to-tail condensation of two molecules of isopentenyl diphosphate with dimethylallyl diphosphate. The enzyme is a homodimer of subunits, typically having two aspartate-rich motifs with two sets of substrate binding sites for an allylic diphosphate and isopentenyl diphosphate per homodimer. The synthase amino-acid residues at the 4th and 5th positions before the first aspartate rich motif mainly determine product specificity. Hypothetically, type I (eukaryotic) and type II (eubacterial) FPPSs evolved from archeal geranylgeranyl diphosphate synthase by substitutions in the chain length determination region. FPPS belongs to enzymes encoded by gene families. In plants this offers the possibility of differential regulation in response to environmental changes or to herbivore or pathogen attack.
Physical description
  • Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland
  • Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland
  • 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.; 264: 19176-84.
  • Ashby MN, Edwards PA. (1990) Elucidation of the deficiency in two yeast coenzyme Q mutants. Characterization of the structural gene encoding hexaprenyl pyrophosphate synthetase. J Biol Chem.; 265: 13157-64.
  • Attucci S, Aitken SM, Gulick PJ, Ibrahim RK. (1995) Farnesyl pyrophosphate synthase from white lupin: molecular cloning, expression, and purification of the expressed protein. Arch Biochem Biophys.; 321: 493-500.
  • Barnard GF, Popjak G. (1981) Human liver prenyltransferase and its characterization.Biochim Biophys Acta.; 661: 87-99.
  • 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: 185-9.
  • 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: 3141-9.
  • 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: 11002-7.
  • Chen A, Kroon PA, Poulter CD. (1994) Isoprenyl diphosphate synthases: protein sequence comparisons of a phylogenetic tree, and prediction of secondary structure. Protein Sci.; 3: 600-7.
  • Clarke CF, Tanaka RD, Svenson K, Wamsley M, Fogelman AM, Edwards PA. (1987) Molecular cloning and sequence of a cholesterol-repressible enzyme related to prenyltransferase in the isoprene biosynthetic pathway. Mol Cell Biol.; 7: 3138-46.
  • Cornforth JW, Cornforth RH, Popjak G, Yengoyan L. (1966) Studies on the biosynthesis of cholesterol. XX. Steric course of decarboxylation of 5-pyrophosphomevalonate and of the carbon to carbon bond formation in the biosynthesis of farnesyl pyrophosphate. J Biol Chem.; 241: 3970-87.
  • Correll CC, Ng L, Edwards PA. (1994) Identification of farnesol as the non-sterol derivative of mevalonic acid required for the accelerated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J Biol Chem.; 269: 17390-3.
  • 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: 7774-80.
  • Cunillera N, Boronat A, Ferrer A. (1997) The Arabidopsis thaliana FPS1 gene generates a novel mRNA that encodes a mitochondrial farnesyl-diphosphate synthase isoform. J Biol Chem.; 272: 15381-8.
  • Dhiman RK, Schulbach MC, Mahapatra S, Baulard AR, Vissa V, Brennan PJ, Crick DC. (2004) Identification of a novel class of omega,E,E-farnesyl diphosphate synthase from Mycobacterium tuberculosis. J Lipid Res.; 45: 1140-7.
  • Eberhardt NL, Rilling HC. (1975) Prenyltransferase from Saccharomyces cerevisiae. Purification to homogeneity and molecular properties. J Biol Chem.; 250: 863-866.
  • Grunler J, Ericsson J, Dallner G. (1994) Branch-point reactions in the biosynthesis of cholesterol, dolichol, ubiquinone and prenylated proteins. Biochim Biophys Acta.; 1212: 259-77.
  • Hemmerlin A, Rivera SB, Erickson HK, Poulter CD. (2003) Enzymes encoded by the farnesyl diphosphate synthase gene family in the Big Sagebrush Artemisia tridentata ssp. spiciformis. J Biol Chem.; 278: 32132-40.
  • Hemmi H, Noike M, Nakayama T, Nishino T. (2003) An alternative mechanism of product chain-length determination in type III geranylgeranyl diphosphate synthase. Eur J Biochem.; 270: 2186-94.
  • Joly A, Edwards PA. (1993) Effect of site-directed mutagenesis of conserved aspartate and arginine residues upon farnesyl diphosphate synthase activity. J Biol Chem.; 268: 26983-9.
  • Kawasaki T, Hamano Y, Kuzuyama T, Itoh N, Seto H, Dairi T. (2003) Interconversion of the product specificity of type I eubacterial farnesyl diphosphate synthase and geranylgeranyl diphosphate synthase through one amino acid substitution. J Biochem (Tokyo).; 133: 83-91.
  • Karst F, Plochocka D, Meyer S, Szkopinska A. (2004) Farnesyl diphosphate synthase activity affects ergosterol level and proliferation of yeast Saccharomyces cerevisiae. Cell Biol Int.; 28: 193-7.
  • Koyama T, Obata S, Osabe M, Takeshita A, Yokoyama K, Uchida M, Nishino T, Ogura K. (1993) Thermostable farnesyl diphosphate synthase of Bacillus stearothermophilus: molecular cloning, sequence determination, overproduction, and purification. J Biochem (Tokyo).; 113: 355-63.
  • Koyama T, Obata S, Osabe M, Saito K, Takeshita A, Nishino T, Ogura K. (1994) Thermostable farnesyl diphosphate synthase of Bacillus stearothermophilus: crystallization and site-directed mutagenesis. Acta Biochim Polon.; 41: 281-92.
  • Koyama T, Tajima M, Nishino T, Ogura K. (1995) Significance of Phe-220 and Gln-221 in the catalytic mechanism of farnesyl diphosphate synthase of Bacillus stearothermophilus. Biochem Biophys Res Commun.; 212: 681-6.
  • Koyama T, Tajima M, Sano H, Doi T, Koike-Takeshita A, Obata S, Nishino T, Ogura K. (1996) Identification of significant residues in the substrate binding site of Bacillus stearothermophilus farnesyl diphosphate synthase. Biochemistry.; 35: 9533-8.
  • Koyama T, Gotoh Y, Nishino T. (2000) Intersubunit location of the active site of farnesyl diphosphate synthase: reconstruction of active enzymes by hybrid-type heteromeric dimers of site-directed mutants. Biochemistry.; 39: 463-9.
  • Laskovics FM, Poulter CD. (1981) Prenyltransferase; determination of the binding mechanism and individual kinetic constants for farnesylpyrophosphate synthetase by rapid quench and isotope partitioning experiments. Biochemistry.; 20: 1893-901.
  • Lynen F, Agranoff BW, Eggerer H, Hennig U, Moslein EM. (1959) γγ-Dimethyl-allyl-pyrophosphat und Geranyl-pyrophosphat, biologische Vorstufen des Squalens. Angew. Chem.; 21: 657-84.
  • Marrero PF, Poulter CD, Edwards PA. (1992) Effects of site-directed mutagenesis of the highly conserved aspartate residues in domain II of farnesyl diphosphate synthase activity. J Biol Chem.; 267: 21873-8.
  • Matsuoka S, Sagami H, Kurisaki A, Ogura K. (1991) Variable product specificity of microsomal dehydrodolichyl diphosphate synthase from rat liver. J Biol Chem.; 266: 3464-8.
  • Mekkriengkrai D, Sando T, Hirooka K, Sakdapipanich J, Tanaka Y, Fukusaki E, Kobayashi A. (2004) Cloning and characterization of farnesyl diphosphate synthase from the rubber-producing mushroom Lactarius chrysorrheus. Biosci Biotechnol Biochem.; 68: 2360-8.
  • Nakane H, Koyama T, Obata S, Osabe M, Takeshita A, Nishino T, Ogura K, Miki K. (1993) Crystallization and preliminary X-ray diffraction studies of Bacillus stearothermophilus farnesyl diphosphate synthase expressed in Escherichia coli. J Mol Biol.; 233: 787-8.
  • Narita K, Ohnuma S, Nishino T. (1999) Protein design of geranyl diphosphate synthase. Structural features that define the product specificities of prenyltransferases. J Biochem (Tokyo).; 126: 566-71.
  • Ohnuma S, Koyama T, Ogura K. (1993) Alteration of the product specificities of prenyltransferases by metal ions. Biochem Biophys Res Commun.; 192: 407-12.
  • Ohnuma S, Nakazawa T, Hemmi H, Hallberg AM, Koyama T, Ogura K, Nishino T. (1996a) Conversion from farnesyl diphosphate synthase to geranylgeranyl diphosphate synthase by random chemical mutagenesis. J Biol Chem.; 271: 10087-95.
  • Ohnuma S, Narita K, Nakazawa T, Ishida C, Takeuchi Y, Ohto C, Nishino T. (1996b) A role of the amino acid residue located on the fifth position before the first aspartate-rich motif of farnesyl diphosphate synthase on determination of the final product. J Biol Chem.; 271: 30748-54.
  • Ohnuma S, Hirooka K, Hemmi H, Ishida C, Ohto C, Nishino T. (1996c) Conversion of product specificity of archaebacterial geranylgeranyl-diphosphate synthase. Identification of essential amino acid residues for chain length determination of prenyltransferase reaction. J Biol Chem.; 271: 18831-7.
  • Ohnuma S, Hirooka K, Ohto C, Nishino T. (1997) Conversion from archaeal geranylgeranyl diphosphate synthase to farnesyl diphosphate synthase. Two amino acids before the first aspartate-rich motif solely determine eukaryotic farnesyl diphosphate synthase activity. J Biol Chem.; 272: 5192-8.
  • Olivier LM, Krisans SK. (2000) Peroxisomal protein targeting and identification of peroxisomal targeting signals in cholesterol biosynthetic enzymes. Biochim Biophys Acta.; 1529: 89-102.
  • Pan Z, Herickhoff L, Backhaus RA. (1996) Cloning, characterization, and heterologous expression of cDNAs for farnesyl diphosphate synthase from the guayule rubber plant reveals that this prenyltransferase occurs in rubber particles. Arch Biochem Biophys.; 332: 196-204.
  • Plochocka D, Karst F, Swiezewska E, Szkopinska A. (2000) The role of ERG20 gene (encoding yeast farnesyl diphosphate synthase) mutation in long dolichol formation. Molecular modeling of FPP synthase. Biochimie.; 82: 733-8.
  • Poulter CD, Rilling HC. (1976) Prenyltransferase: the mechanism of the reaction. Biochemistry.; 15: 1079-83.
  • Reed BC, Rilling HC. (1975) Crystallization and partial characterization of prenyltransferase from avian liver. Biochemistry.; 14: 50-4.
  • Reilly JF, Martinez SD, Mickey G, Maher PA. (2002) A novel role of farnesyl pyrophosphate synthase in fibroblast growth factor-mediated signal transduction. Biochem J.; 366: 501-10.
  • Roos W, Evers S, Hieke M, Tschope M, Schumann B. (1998) Shifts of intracellular pH distribution as a part of the signal mechanism leading to the elicitation of benzophenanthridine alkaloids. Phytoalexin biosynthesis in cultured cells of Eschscholtzia californica Plant Physiol.; 118: 349-64.
  • Runquist M, Ericsson J, Thelin A, Chojnacki T, Dallner G. (1994) Isoprenoid biosynthesis in rat liver mitochondria. Studies on farnesyl pyrophosphate synthase and trans-prenyltransferase. J Biol Chem.; 269: 5804-9.
  • Sanmiya K, Ueno O, Matsuoka M, Yamamoto N. (1999) Localization of farnesyl diphosphate synthase in chloroplasts. Plant Cell Physiol.; 40: 348-54.
  • Shearer A, Hampton RY. (2005) Lipid mediated, reversible misfolding of sterol-sensing domain protein. EMBO J.; 24: 149-59.
  • Shivdasani RA, Rosenblatt MF, Zucker-Franklin D, Jackson CW, Hunt P, Saris CJ, Orkin SH. (1995) Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development. Cell.; 81: 695-704.
  • Song L, Poulter CD. (1994) Yeast farnesyl-diphosphate synthase: site-directed mutagenesis of residues in highly conserved prenyltransferase domains I and II. Proc Natl Acad Sci USA.; 91: 3044-8.
  • Stanley Fernandez SM, Kellogg BA, Poulter CD. (2000) Farnesyl diphosphate synthase. Altering the catalytic site to select for geranyl diphosphate activity. Biochemistry.; 39: 15316-21.
  • Tachibana A, Yano Y, Otani S, Nomura N, Sako Y, Taniguchi M. (2000) Novel prenyltransferase gene encoding farnesylgeranyl diphosphate synthase from a hyperthermophilic archaeon, Aeropyrum pernix. Molecular evolution with alteration in product specificity. Eur J Biochem.; 267: 321-8.
  • Tarshis LC, Yan M, Poulter CD, Sacchettini JC. (1994) Crystal structure of recombinant farnesyl diphosphate synthase at 2.6 Å resolution. Biochemistry.; 33: 10871-7.
  • Tarshis LC, Proteau PJ, Kellogg BA, Sacchettini JC, Poulter CD. (1996) Regulation of product chain length by isoprenyl diphosphate synthases. Proc Natl Acad Sci USA.; 93: 15018-23.
  • Trapp SC, Croteau RB. (2001) Genomic organization of plant terpene synthases and molecular evolutionary implications. Genetics.; 158: 811-32.
  • Wilkin DJ, Kutsunai SY, Edwards PA. (1990) Isolation and sequence of the human farnesyl pyrophosphate synthetase cDNA. Coordinate regulation of the mRNAs for farnesyl pyrophosphate synthetase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and 3-hydroxy-3-methylglutaryl coenzyme A synthase by phorbol ester. J Biol Chem.; 265: 4607-14.
  • Yeh LS, Rilling HC. (1977) Purification and properties of pig liver prenyltransferase: interconvertible forms of the enzyme. Arch Biochem Biophys.; 183: 718-25.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.