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MetaCyc Pathway: superpathway of ubiquinol-8 biosynthesis (prokaryotic)

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

Synonyms: superpathway of ubiquinone-8 biosynthesis (prokaryotic)

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis Quinol and Quinone Biosynthesis Ubiquinol Biosynthesis
Superpathways

Some taxa known to possess this pathway include ? : Acinetobacter calcoaceticus anitratus , Acinetobacter lwoffii , Aeromonas caviae , Aeromonas hydrophila , Allochromatium vinosum , Azotobacter chroococcum , Azotobacter vinelandii , Bordetella pertussis , Citrobacter freundii , Cupriavidus necator , Enterobacter aerogenes , Escherichia coli K-12 substr. MG1655 , Halorhodospira halophila , Proteus mirabilis , Proteus vulgaris , Rubrivivax gelatinosus , Salinivibrio costicola , Serratia marcescens , Stenotrophomonas maltophilia , Xanthomonas campestris , Xanthomonas citri , Xanthomonas oryzae

Expected Taxonomic Range: Bacteria

Summary:
General Background

Ubiquinone (also known as coenzyme Q) is an isoprenoid quinone that functions as an electron carrier in membranes. In eukaryotes ubiquinone is found mostly within the inner mitochondrial membrane, where it functions in respiratory electron transport, transferring two electrons from either complex I (NADH dehydrogenase) or complex II (succinate-ubiquinone reductase) to complex III (bc1 complex). The quinone nucleus of ubiquinone is derived directly from 4-hydroxybenzoate, while the isoprenoid subunits of the polyisoprenoid tail are synthesized via the methylerythritol phosphate pathway I, which feeds isoprene units into the Polyprenyl Biosynthesis pathways.

The number of isoprenoid subunits in the ubiquinone side chain vary in different species. For example, Saccharomyces cerevisiae has 6 such subunits, Escherichia coli K-12 has 8, rat and mouse have 9, and Homo sapiens has 10. The ubiquinones are often named according to the number of carbons in the side chain (e.g. ubi-30) or the number of isoprenoid subunits (e.g. Q-10).

Following addition of the polyprenyl tail, the product (4-hydroxy-3-polyprenylbenzoate), is processed in three steps, namely decarboxylation, oxidation, and methylation. The prokaryotic and eukaryotic pathways differ in the order of these steps: in eukaryotes the compound is oxidized and methylated prior to decarboxylation; in prokaryotes the compound is first decarboxylated, followed by oxidation and methylation [Shepherd96].

The ubiquinone biosynthesis pathway has been elucidated primarily by the use of mutant strains that accumulate pathway intermediates; some of the enzymes in this pathway have not been biochemically characterized.

About This Pathway

ubiquinone-8 (Q-8) is a common form of ubiquinone among bacteria. Most of the Gram-negative facultative anaerobes, such as the enterobacteria, produce Q-8 (in addition to menaquinone-8 and demethylmenaquinone-8). Q-8 has been documented in several strains of Escherichia coli [Lester59], Citrobacter freundii, Enterobacter aerogenes, Pectobacterium carotovorum, Proteus mirabilis, Proteus vulgaris [Whistance69] and Serratia marcescens [Bezborodov69], as well as in the non-eneterobacteria Aeromonas hydrophila, Aeromonas caviae [Whistance69] and Salinivibrio costicola [Collins81a]. It is also common in aerobic Gram-negative bacteria, including Azotobacter vinelandii [Lester59, Jones66], Azotobacter chroococcum [Bishop62], Acinetobacter calcoaceticus anitratus [Denis75], Bordetella pertussis [Thiele73], Cupriavidus necator [Yamada68], and various Xanthomonas strains [Ikemoto80]. Q-8 was also found to be the major quinone in an unidentified strain of the gliding bacterium Beggiatoa [Carr67] and in some phototrophic bacteria, including Allochromatium vinosum [Osnitskaya64], Halorhodospira halophila, Rubrivivax gelatinosus [Carr65, Maroc68], and a strain of Rhodospirillum [Maroc68]. Q-8 is often found as a secondary quinone in Pseudomonas strains [Whistance69].

The best studied ubiquinone biosynthesis pathway is that of Escherichia coli K-12, which produces a ubiquinone-8. The first committed step of the pathway is the conversion of chorismate to 4-hydroxybenzoate by chorismate lyase. The enzyme retains and is efficiently inhibited by the product of the reaction, 4-hydroxybenzoate, which may present a control mechanism for the ubiquinone biosynthesis pathway or a mechanism for delivery of 4-hydroxybenzoate to the membrane [Gallagher01, Holden02].

The second step in the pathway is the transfer of the polyisoprenoid tail onto 4-hydroxybenzoate by the membrane-bound 4-hydroxybenzoate octaprenyltransferase. This is followed by the decarboxylation of the ring structure by 3-octaprenyl-4-hydroxybenzoate carboxy-lyase (or possibly by UbiX) to form 2-octaprenylphenol. Under anaerobic conditions, this compound accumulates in the membrane and is not converted into ubiquinone. Further steps in the pathway require the presence of dioxygen [Knoell78].

Following is the alternating introduction of three hydroxyl- and three methyl groups. With the exception of the methyltransferase that catalyzes both of the O-methyltransferase reactions, UbiG, none of the enzymes have been studied biochemically and their substrate and cofactor requirements are still unknown.

The enzymes of this pathway may form a membrane-associated complex [Knoell79]. UbiX shows a genetic interaction with UbiG, suggesting a possible physical interaction within a complex [Gulmezian06].

For the biosynthesis of ubiquinone-8 in yeast, see ubiquinol-8 biosynthesis (eukaryotic).

Superpathways: superpathway of chorismate metabolism

Subpathways: octaprenyl diphosphate biosynthesis , ubiquinol-8 biosynthesis (prokaryotic)

Unification Links: EcoCyc:UBISYN-PWY

Credits:
Created 01-Feb-1995 by Riley M , Marine Biological Laboratory
Last-Curated ? 16-Jul-2007 by Keseler I , SRI International


References

Bezborodov69: Bezborodov, A. M., Chermenskaya, T.S. (1969). "Biosynthesis of 8-ubiquinone and vitamin K2(40) by Serratia marcescens strain 42." Prikl. Biokhim. Mikrobiol. 5:620-623.

Bishop62: Bishop, D.H., Pandya, K.P., King, H.K. (1962). "Ubiquinone and vitamin K in bacteria." Biochem J 83;606-14. PMID: 13869492

Carr65: Carr, N. G., Exell, G. (1965). "Ubiquinone concentrations in Athiorhodaceae grown under various environmental conditions." Biochem. J. 96:688-692.

Carr67: Carr, N. G., Exell, G., Flynn, V., Hallaway, M., Talukdar, S. (1967). "Minor quinones of some Myxophyceae." Arch. Biochem. Biophys. 120:503-507.

Collins81a: Collins, M.D., Ross, H. N. M., Tindall, B. J., Grant, W. D. (1981). "Distribution of isoprenoid quinones in halophilic bacteria." J. Appl. Bacteriol. 50:559-565.

Denis75: Denis, F. A., D'Oultrement, P. A., Debacq, J. J., Cherel, J. M., Brisou, J. (1975). "Distribution des ubiquinones (coenzyme Q) chez les bacilles a gram negatif." C. R. Soc. Biol. 169:380-383.

Gallagher01: Gallagher DT, Mayhew M, Holden MJ, Howard A, Kim KJ, Vilker VL (2001). "The crystal structure of chorismate lyase shows a new fold and a tightly retained product." Proteins 44(3);304-11. PMID: 11455603

Gulmezian06: Gulmezian M, Zhang H, Javor GT, Clarke CF (2006). "Genetic evidence for an interaction of the UbiG O-methyltransferase with UbiX in Escherichia coli coenzyme Q biosynthesis." J Bacteriol 188(17);6435-9. PMID: 16923914

Holden02: Holden MJ, Mayhew MP, Gallagher DT, Vilker VL (2002). "Chorismate lyase: kinetics and engineering for stability." Biochim Biophys Acta 1594(1);160-7. PMID: 11825618

Ikemoto80: Ikemoto, S., Suzuki, K., Kaneko, T., Komagata, K. (1980). "Characterization of strains of Pseudomonas maltophilia which do not require methionine." Int. J. Syst. Bacteriol. 30:437-447.

Jones66: Jones CW, Redfearn ER (1966). "Electron transport in Azotobacter vinelandii." Biochim Biophys Acta 113(3);467-81. PMID: 4288128

Knoell78: Knoell HE, Kraft R, Knappe J (1978). "Dioxygen and temperature dependence of ubiquinone formation in Escherichia coli: studies of cells charged with 2-octaprenyl phenol." Eur J Biochem 90(1);107-12. PMID: 361395

Knoell79: Knoell HE (1979). "Isolation of a soluble enzyme complex comprising the ubiquinone-8 synthesis apparatus from the cytoplasmic membrane of Escherichia coli." Biochem Biophys Res Commun 91(3);919-25. PMID: 393264

Lester59: Lester, R.L., Crane, F.L. (1959). "The natural occurrence of coenzyme Q and related compounds." J Biol Chem 234(8);2169-75. PMID: 13673033

Maroc68: Maroc J, de Klerk H, Kamen MD (1968). "Quinones of Athiorhodaceae." Biochim Biophys Acta 162(4);621-3. PMID: 5727384

Meganathan01: Meganathan R (2001). "Ubiquinone biosynthesis in microorganisms." FEMS Microbiol Lett 203(2);131-9. PMID: 11583838

Osnitskaya64: Osnitskaya, L.K., Threlfall, D.R., Goodwin, T.W. (1964). "Ubiquinone-40 and vitamin K-2 (40) in Chromatium vinosum." Nature 204;80-1. PMID: 14240125

Shepherd96: Shepherd, J. A., Poon, W. W., Myles, D. C., Clarke, C. F. (1996). "The biosynthesis of ubiquinone: synthesis and enzymatic modification of biosynthetic precursors." Tetrahedron Lett. 37(14):2395-2398.

Thiele73: Thiele OW, Schwinn G (1973). "The free lipids of Brucella melitensis and Bordetella pertussis." Eur J Biochem 34(2);333-44. PMID: 4351160

Whistance69: Whistance GR, Dillon JF, Threlfall DR (1969). "The nature, intergeneric distribution and biosynthesis of isoprenoid quinones and phenols in gram-negative bacteria." Biochem J 111(4);461-72. PMID: 4886765

Yamada68: Yamada, Y., Aida, K., Uemura, T. (1968). "Distribution of ubiquinone-10 and -9 in acetic acid bacteria and its relation to the classification of genera Gluconobacter and Acetobacter, especially the so-called intermediate strains." Agric. Biol. Chem. 32:786-788.

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

Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554

Alexander78: Alexander K, Young IG (1978). "Alternative hydroxylases for the aerobic and anaerobic biosynthesis of ubiquinone in Escherichia coli." Biochemistry 17(22);4750-5. PMID: 365223

Asai94: Asai K, Fujisaki S, Nishimura Y, Nishino T, Okada K, Nakagawa T, Kawamukai M, Matsuda H (1994). "The identification of Escherichia coli ispB (cel) gene encoding the octaprenyl diphosphate synthase." Biochem Biophys Res Commun 202(1);340-5. PMID: 8037730

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

Bairoch93: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Baisa13: Baisa G, Stabo NJ, Welch RA (2013). "Characterization of Escherichia coli D-cycloserine transport and resistant mutants." J Bacteriol 195(7);1389-99. PMID: 23316042

Brauer04: Brauer L, Brandt W, Wessjohann LA (2004). "Modeling the E. coli 4-hydroxybenzoic acid oligoprenyltransferase ( ubiA transferase) and characterization of potential active sites." J Mol Model 10(5-6);317-27. PMID: 15597200

Brauer08: Brauer L, Brandt W, Schulze D, Zakharova S, Wessjohann L (2008). "A structural model of the membrane-bound aromatic prenyltransferase UbiA from E. coli." Chembiochem 9(6);982-92. PMID: 18338424

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Britton97: Britton RA, Lupski JR (1997). "Isolation and characterization of suppressors of two Escherichia coli dnaG mutations, dnaG2903 and parB." Genetics 145(4);867-75. PMID: 9093842

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

Chang12: Chang KM, Chen SH, Kuo CJ, Chang CK, Guo RT, Yang JM, Liang PH (2012). "Roles of amino acids in the Escherichia coli octaprenyl diphosphate synthase active site probed by structure-guided site-directed mutagenesis." Biochemistry 51(16);3412-9. PMID: 22471615

Choi09: Choi JH, Ryu YW, Park YC, Seo JH (2009). "Synergistic effects of chromosomal ispB deletion and dxs overexpression on coenzyme Q(10) production in recombinant Escherichia coli expressing Agrobacterium tumefaciens dps gene." J Biotechnol 144(1);64-9. PMID: 19409940

Collins81: Collins MD, Jones D (1981). "Distribution of isoprenoid quinone structural types in bacteria and their taxonomic implication." Microbiol Rev 45(2);316-54. PMID: 7022156

Collis89: Collis CM, Grigg GW (1989). "An Escherichia coli mutant resistant to phleomycin, bleomycin, and heat inactivation is defective in ubiquinone synthesis." J Bacteriol 1989;171(9);4792-8. PMID: 2475481

Cox68: Cox GB, Gibson F, Pittard J (1968). "Mutant strains of Escherichia coli K-12 unable to form ubiquinone." J Bacteriol 95(5);1591-8. PMID: 4870277

Cox69: Cox GB, Young IG, McCann LM, Gibson F (1969). "Biosynthesis of ubiquinone in Escherichia coli K-12: location of genes affecting the metabolism of 3-octaprenyl-4-hydroxybenzoic acid and 2-octaprenylphenol." J Bacteriol 99(2);450-8. PMID: 4897112

Cui10: Cui TZ, Kaino T, Kawamukai M (2010). "A subunit of decaprenyl diphosphate synthase stabilizes octaprenyl diphosphate synthase in Escherichia coli by forming a high-molecular weight complex." FEBS Lett 584(4);652-6. PMID: 20051244

Daley05: Daley DO, Rapp M, Granseth E, Melen K, Drew D, von Heijne G (2005). "Global topology analysis of the Escherichia coli inner membrane proteome." Science 308(5726);1321-3. PMID: 15919996

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

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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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