Escherichia coli K-12 substr. MG1655 Pathway: superpathway of ubiquinol-8 biosynthesis (prokaryotic)
Inferred from experiment

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

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

Locations of Mapped Genes:

Schematic showing all replicons, marked with selected genes

Genetic Regulation Schematic

Genetic regulation schematic for superpathway of ubiquinol-8 biosynthesis (prokaryotic)

Synonyms: superpathway of ubiquinone-8 biosynthesis (prokaryotic)

Superclasses: BiosynthesisCofactors, Prosthetic Groups, Electron Carriers BiosynthesisQuinol and Quinone BiosynthesisUbiquinol 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 [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. 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.

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].

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].

Reviews: [Neidhardt96, Soballe99, Meganathan01, Meganathan01a]

Superpathways: superpathway of chorismate metabolism

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

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


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

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

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

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

Meganathan01a: Meganathan R (2001). "Biosynthesis of menaquinone (vitamin K2) and ubiquinone (coenzyme Q): a perspective on enzymatic mechanisms." Vitam Horm 61;173-218. PMID: 11153266

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.

Soballe99: Soballe B, Poole RK (1999). "Microbial ubiquinones: multiple roles in respiration, gene regulation and oxidative stress management." Microbiology 145 ( Pt 8);1817-30. PMID: 10463148

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

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

Aussel14: Aussel L, Pierrel F, Loiseau L, Lombard M, Fontecave M, Barras F (2014). "Biosynthesis and physiology of coenzyme Q in bacteria." Biochim Biophys Acta 1837(7);1004-11. PMID: 24480387

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.

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

Clarke15: Clarke CF, Allan CM (2015). "Biochemistry: Unexpected role for vitamin B2." Nature 522(7557);427-8. PMID: 26083748

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

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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