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|
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:
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 [Gallagher01a, 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.
Superpathways: superpathway of chorismate metabolism
Unification Links: EcoCyc:UBISYN-PWY
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.
Gallagher01a: 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
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
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.
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.
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
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
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
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
Choi09a: 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
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
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
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