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Pathway Description
Secondary Metabolites: Ubiquinol Biosynthesis
Escherichia coli
Metabolic Pathway
The biosynthesis of ubiquinol starts the interaction of 4-hydroxybenzoic acid interacting with an octaprenyl diphosphate. The former compound comes from the chorismate interacting with a chorismate lyase resulting in the release of a pyruvic acid and a 4-hydroxybenzoic acid. On the other hand, the latter compound, octaprenyl diphosphate is the result of a farnesyl pyrophosphate interacting with an isopentenyl pyrophosphate through an octaprenyl diphosphate synthase resulting in the release of a pyrophosphate and an octaprenyl diphosphate.
The 4-hydroxybenzoic acid interacts with octaprenyl diphosphate through a 4-hydroxybenzoate octaprenyltransferase resulting in the release of a pyrophosphate and a 3-octaprenyl-4-hydroxybenzoate. The latter compound then interacts with a hydrogen ion through a 3-octaprenyl-4-hydroxybenzoate carboxy-lyase resulting in the release of a carbon dioxide and a 2-octaprenylphenol. The latter compound interacts with an oxygen molecule and a hydrogen ion through a NADPH driven 2-octaprenylphenol hydroxylase resulting in a NADP, a water molecule and a 2-octaprenyl-6-hydroxyphenol.
The 2-octaprenyl-6-hydroxyphenol interacts with an S-adenosylmethionine through a bifunctional 3-demethylubiquinone-8 3-O-methyltransferase and 2-octaprenyl-6-hydroxyphenol methylase resulting in the release of a hydrogen ion, an s-adenosylhomocysteine and a 2-methoxy-6-(all-trans-octaprenyl)phenol. The latter compound then interacts with an oxygen molecule and a hydrogen ion through a NADPH driven 2-octaprenyl-6-methoxyphenol hydroxylase resulting in a NADP, a water molecule and a 2-methoxy-6-all trans-octaprenyl-2-methoxy-1,4-benzoquinol.
The latter compound interacts with a S-adenosylmethionine through a bifunctional 2-octaprenyl-6-methoxy-1,4-benzoquinone methylase and S-adenosylmethionine:2-DMK methyltransferase resulting in a s-adenosylhomocysteine, a hydrogen ion and a 6-methoxy-3-methyl-2-all-trans-octaprenyl-1,4-benzoquinol. The 6-methoxy-3-methyl-2-all-trans-octaprenyl-1,4-benzoquinol. interacts with a reduced acceptor, an oxygen molecule through a 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone hydroxylase resulting in the release of a water molecule, an oxidized electron acceptor and a 3-demethylubiquinol-8. The latter compound then interacts with a S-adenosylmethionine through a bifunctional 3-demethylubiquinone-8 3-O-methyltransferase and 2-octaprenyl-6-hydroxyphenol methylase resulting in a hydrogen ion, a S-adenosylhomocysteine and a ubiquinol 8.
References
Secondary Metabolites: Ubiquinol Biosynthesis References
KEGG: http://www.genome.jp/kegg-bin/show_module?M00117
Alexander K, Young IG: Alternative hydroxylases for the aerobic and anaerobic biosynthesis of ubiquinone in Escherichia coli. Biochemistry. 1978 Oct 31;17(22):4750-5.
Pubmed: 365223
Gallagher DT, Mayhew M, Holden MJ, Howard A, Kim KJ, Vilker VL: The crystal structure of chorismate lyase shows a new fold and a tightly retained product. Proteins. 2001 Aug 15;44(3):304-11.
Pubmed: 11455603
Gulmezian M, Zhang H, Javor GT, Clarke CF: Genetic evidence for an interaction of the UbiG O-methyltransferase with UbiX in Escherichia coli coenzyme Q biosynthesis. J Bacteriol. 2006 Sep;188(17):6435-9. doi: 10.1128/JB.00668-06.
Pubmed: 16923914
Holden MJ, Mayhew MP, Gallagher DT, Vilker VL: Chorismate lyase: kinetics and engineering for stability. Biochim Biophys Acta. 2002 Jan 31;1594(1):160-7.
Pubmed: 11825618
Knoell HE, Kraft R, Knappe J: Dioxygen and temperature dependence of ubiquinone formation in Escherichia coli: studies of cells charged with 2-octaprenyl phenol. Eur J Biochem. 1978 Sep 15;90(1):107-12.
Pubmed: 361395
Knoell HE: Isolation of a soluble enzyme complex comprising the ubiquinone-8 synthesis apparatus from the cytoplasmic membrane of Escherichia coli. Biochem Biophys Res Commun. 1979 Dec 14;91(3):919-25.
Pubmed: 393264
Meganathan R: Ubiquinone biosynthesis in microorganisms. FEMS Microbiol Lett. 2001 Sep 25;203(2):131-9.
Pubmed: 11583838
Meganathan R: Biosynthesis of menaquinone (vitamin K2) and ubiquinone (coenzyme Q): a perspective on enzymatic mechanisms. Vitam Horm. 2001;61:173-218.
Pubmed: 11153266
Soballe B, Poole RK: Microbial ubiquinones: multiple roles in respiration, gene regulation and oxidative stress management. Microbiology. 1999 Aug;145 ( Pt 8):1817-30. doi: 10.1099/13500872-145-8-1817.
Pubmed: 10463148
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