If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
Synonyms: superpathway of ubiquinone-8 biosynthesis (prokaryotic)
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Quinol and Quinone Biosynthesis → Ubiquinol Biosynthesis|
Ubiquinone is an isoprenoid quinone that functions as an electron carrier in the membrane. The quinone nucleus of ubiquinone is derived directly from chorismate, and the isoprenoid subuntis of the polyisoprenoid tail are synthesized via the methylerythritol phosphate pathway I which feeds isoprene units into the polyisoprenoid biosynthesis (E. coli) pathway. Ubiquinone biosynthesis has primarily been elucidated by the use of mutant strains that accumulate pathway intermediates; many of the enzymes in this pathway have not been biochemically characterized.
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. The reactions catalyzed by the three hydroxylases are particularly intriguing, but again none of them have been studied biochemically; thus, their substrate and cofactor requirements are unknown.
Under anaerobic conditions, alternate enzymes must perform the hydroxylation steps that are carried out by UbiB, UbiH, and UbiF under aerobic conditions. No enzymes of the proposed anaerobic pathway have been identified [Alexander78].
Superpathways: superpathway of chorismate metabolism
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
Neidhardt96: Neidhardt FC, Curtiss III R, Ingraham JL, Lin ECC, Low Jr KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE "Escherichia coli and Salmonella, Cellular and Molecular Biology, Second Edition." American Society for Microbiology, Washington, D.C., 1996.
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
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
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
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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