Escherichia coli K-12 substr. MG1655 Pathway: guanine and guanosine salvage

Pathway diagram: guanine and guanosine salvage

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 guanine and guanosine salvage

Superclasses: BiosynthesisNucleosides and Nucleotides BiosynthesisPurine Nucleotide BiosynthesisPurine Nucleotide SalvageGuanine and Guanosine Salvage

General Background

Guanosine nucleotides can be synthesized de novo as shown in pathway superpathway of guanosine nucleotides de novo biosynthesis II. In that route GMP is synthesized via IMP and XMP, which is converted to GMP by the action of GMP synthetase, an enzyme that can use either glutamine or ammonia as substrate. Note that the free base guanine or the ribonucleoside guanosine are not produced via the de novo biosynthesis pathway.

Many organisms can also recycle guanosine nucleotides by a combination of degradation and salvage pathways. The degradation pathway is responsible for degradation of the nucleotides to the nucleoside guanosine and the base guanine, which can be further degraded via xanthine and urate (see pathway guanosine nucleotides degradation III). In some organisms urate is catabolized to basic building blocks (see MetaCyc pathway urate degradation to allantoin I). However, both guanosine and guanine can be salvaged by certain enzymes and converted back to their nucleotide form as shown in this pathway and pathway guanine and guanosine salvage III. In Escherichia coli the pathway shown here is the major salvage route.

About This Pathway

In E. coli phosphorolytic cleavage of the N-glycosyl bond of of purine ribonucleosides or deoxyribonucleosides, as shown here for guanosine, is catalyzed by the purine nucleoside phosphorylases encoded by genes deoD and xapA. The released purine base, in this case guanine, is subsequently converted to a nucleotide, in this case GMP, by the action of phosphoribosyltransferases encoded by genes gpt and hpt.

DeoD is the classical purine nucleoside phosphorylase I. It utilizes guanosine, adenosine, or inosine (or their corresponding deoxyribonucleosides) as substrate. Synthesis of this enzyme is induced in the presence of deoxyribonucleosides, inosine, or guanosine in the growth medium. As shown here it cleaves guanosine to guanine and α-D-ribose-1-phosphate. XapA (xanthosine phosphorylase) cleaves 6-oxopurine ribonucleosides and deoxyribonucleosides and is induced after exposure of cells to xanthosine in the medium [HammerJespersen80].

In the second step, the two phosphoribosyltransferases Hpt and Gpt salvage 6-oxopurine bases. Gpt and Hpt utilize 5-phospho-α-D-ribose 1-diphosphate to convert the free base guanine to the mononucleotide GMP. As shown in Salmonella typhimurium, together these enzymes can rescue all 6-oxopurine bases [Gots72].

Review: Jensen, K.F., G. Dandanell, B. Hove-Jensen and M. Willemoes (2008) "Nucleotides, Nucleosides and Nucleobases" EcoSal 3.6.2 [ECOSAL]

Superpathways: superpathway of guanine and guanosine salvage

Variants: guanine and guanosine salvage III

Created 20-Aug-2010 by Caspi R, SRI International


ECOSAL: "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

Gots72: Gots JS, Benson CE, Shumas SR (1972). "Genetic separation of hypoxanthine and guanine-xanthine phosphoribosyltransferase activities by deletion mutations in Salmonella typhimurium." J Bacteriol 112(2);910-6. PMID: 4563984

HammerJespersen80: Hammer-Jespersen K, Buxton RS, Hansen TD (1980). "A second purine nucleoside phosphorylase in Escherichia coli K-12. II. Properties of xanthosine phosphorylase and its induction by xanthosine." Mol Gen Genet 1980;179(2);341-8. PMID: 7007809

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

Ahmad68: Ahmad SI, Barth PT, Pritchard RH (1968). "Properties of a mutant of Escherichia coli lacking purine nucleoside phosphorylase." Biochim Biophys Acta 161(2);581-3. PMID: 4875425

Bennett03: Bennett EM, Li C, Allan PW, Parker WB, Ealick SE (2003). "Structural basis for substrate specificity of Escherichia coli purine nucleoside phosphorylase." J Biol Chem 278(47);47110-8. PMID: 12937174

Bennett03a: Bennett EM, Anand R, Allan PW, Hassan AE, Hong JS, Levasseur DN, McPherson DT, Parker WB, Secrist JA, Sorscher EJ, Townes TM, Waud WR, Ealick SE (2003). "Designer gene therapy using an Escherichia coli purine nucleoside phosphorylase/prodrug system." Chem Biol 10(12);1173-81. PMID: 14700625

Bertoša14: Bertoša B, Mikleušević G, Wielgus-Kutrowska B, Narczyk M, Hajnic M, Leščić Ašler I, Tomic S, Luic M, Bzowska A (2014). "Homooligomerization is needed for stability: a molecular modelling and solution study of Escherichia coli purine nucleoside phosphorylase." FEBS J 281(7);1860-71. PMID: 24785777

Bezirdzhian86: Bezirdzhian KhO, Kocharian ShM, Akopian ZhI (1986). "[Isolation of the hexameric form of purine nucleoside phosphorylase from E. coli. Comparative study of trimeric and hexameric forms of the enzyme]." Biokhimiia 1986;51(7);1085-92. PMID: 3089333

Bezirdzhian87: Bezirdzhian KhO, Kocharian ShM, Akopian ZhI (1987). "[Hexamere purine nucleoside phosphorylase from Escherichia coli K-12. Kinetic analysis and mechanism of reaction]." Biokhimiia 52(11);1770-6. PMID: 3125860

Bezirdzhian87a: Bezirdzhian KhO, Kocharian ShM, Akopian ZhI (1987). "[Hexameric purine nucleoside phosphorylase II from Escherichia coli K-12. Physico-chemical and catalytic properties and stabilization with substrates]." Biokhimiia 1987;52(10);1624-31. PMID: 3122852

Buxton75: Buxton RS (1975). "Genetic analysis of thymidine-resistant and low-thymine-requiring mutants of Escherichia coli K-12 induced by bacteriophage Mu-1." J Bacteriol 121(2);475-84. PMID: 1089630

Buxton80: Buxton RS, Hammer-Jespersen K, Valentin-Hansen P (1980). "A second purine nucleoside phosphorylase in Escherichia coli K-12. I. Xanthosine phosphorylase regulatory mutants isolated as secondary-site revertants of a deoD mutant." Mol Gen Genet 179(2);331-40. PMID: 7007808

Bzowska00: Bzowska A, Kulikowska E, Shugar D (2000). "Purine nucleoside phosphorylases: properties, functions, and clinical aspects." Pharmacol Ther 88(3);349-425. PMID: 11337031

Bzowska88: Bzowska A, Kulikowska E, Darzynkiewicz E, Shugar D (1988). "Purine nucleoside phosphorylase. Structure-activity relationships for substrate and inhibitor properties of N-1-, N-7-, and C-8-substituted analogues; differentiation of mammalian and bacterial enzymes with N-1-methylinosine and guanosine." J Biol Chem 263(19);9212-7. PMID: 3132457

Dandanell05: Dandanell G, Szczepanowski RH, Kierdaszuk B, Shugar D, Bochtler M (2005). "Escherichia coli purine nucleoside phosphorylase II, the product of the xapA gene." J Mol Biol 348(1);113-25. PMID: 15808857

Deo85: Deo SS, Tseng WC, Saini R, Coles RS, Athwal RS (1985). "Purification and characterization of Escherichia coli xanthine-guanine phosphoribosyltransferase produced by plasmid pSV2gpt." Biochim Biophys Acta 839(3);233-9. PMID: 3886014

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

Ding10: Ding QB, Ou L, Wei DZ, Wei XK, Xu YM, Zhang CY (2010). "Enzymatic synthesis of nucleosides by nucleoside phosphorylase co-expressed in Escherichia coli." J Zhejiang Univ Sci B 11(11);880-8. PMID: 21043057

Dong14: Dong WR, Sun CC, Zhu G, Hu SH, Xiang LX, Shao JZ (2014). "New function for Escherichia coli xanthosine phophorylase (xapA): genetic and biochemical evidences on its participation in NAD(+) salvage from nicotinamide." BMC Microbiol 14;29. PMID: 24506841

Fateev15: Fateev IV, Kharitonova MI, Antonov KV, Konstantinova ID, Stepanenko VN, Esipov RS, Seela F, Temburnikar KW, Seley-Radtke KL, Stepchenko VA, Sokolov YA, Miroshnikov AI, Mikhailopulo IA (2015). "Recognition of Artificial Nucleobases by E. coli Purine Nucleoside Phosphorylase versus its Ser90Ala Mutant in the Synthesis of Base-Modified Nucleosides." Chemistry 21(38);13401-13419. PMID: 26230190

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

Ge09: Ge C, OuYang L, Ding Q, Ou L (2009). "Co-expression of recombinant nucleoside phosphorylase from Escherichia coli and its application." Appl Biochem Biotechnol 159(1);168-77. PMID: 19099210

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by Pathway Tools version 19.5 (software by SRI International) on Wed May 4, 2016, biocyc13.