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Escherichia coli K-12 substr. MG1655 Pathway: anhydromuropeptides recycling

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

Locations of Mapped Genes:

Genetic Regulation Schematic: ?

Synonyms: 1,6-anhydro-N-acetylmuramic acid recycling, cell wall recycling

Superclasses: Degradation/Utilization/Assimilation Secondary Metabolites Degradation Sugar Derivatives Degradation

Summary:
Anhydromuropeptides (mainly GlcNAc-1,6-anhMurNAc-L-Ala-γ-D-Glu-DAP-D-Ala) are steadily released during growth by lytic transglycosylases and endopeptidases and imported back into the cytoplasm for recycling. During bacterial growth, a very large proportion of the peptidoglycan polymer is degraded and reused in a process termed cell wall recycling. for example, the Gram-negative bacterium Escherichia coli recovers about half of its cell wall within one generation [Park08, Johnson13].

The anhydromuropeptides are imported by the ampG-encoded muropeptide:H+ symporter. Once inside the cytoplasm, the anhydromuropeptides are hydrolyzed by EC 3.5.1.28, N-acetylmuramoyl-L-alanine amidase (ampD), EC 3.2.1.52, β-N-acetylhexosaminidase (nagZ) and L,D-carboxypeptidase A (ldcA), yielding N-acetyl-β-D-glucosamine, 1,6-anhydro-N-acetyl-β-muramate, L-alanyl-γ-D-glutamyl-meso-diaminopimelate and D-alanine [Goodell85].

1,6-anhydro-N-acetyl-β-muramate is phosphorylated by EC 2.7.1.170, anhydro-N-acetylmuramic acid kinase (anmK) and then converted into N-acetyl-D-glucosamine 6-phosphate by EC 4.2.1.126, N-acetylmuramic acid 6-phosphate etherase (murQ). This is a branch point, as this compound could be directed either for further degradation (see pathways of N-acetylglucosamine degradation) or for recycling into new peptidoglycan monomers, as described in this pathway [Uehara05, Jaeger05]. The final product of this pathway, UDP-N-α-D-acetylmuramate, is one of the precursors for peptidoglycan biosynthesis.

The tripeptide L-alanyl-γ-D-glutamyl-meso-diaminopimelate, which is generated by EC 3.4.17.13, muramoyltetrapeptide carboxypeptidase, can be degraded further, as described in muropeptide degradation. However, the vast majority is recycled by muropeptide ligase (mpl). This enzyme is a dedicated recycling enzyme that attaches the recovered Ala-Glu-DAP tripeptide to UDP-N-α-D-acetylmuramate, thereby substituting three amino acid ligases of the peptidoglycan de novo biosynthetic pathway [MenginLecreulx96].

Although exogenously provided 1,6-anhydro-N-acetyl-β-muramate can be taken up by Escherichia coli, it can not serve as the sole source of carbon for growth, suggesting that it may be toxic to the cell [Uehara06].

Credits:
Created 02-Sep-2005 by Keseler I , SRI International
Revised 15-Oct-2013 by Caspi R , SRI International


References

Goodell85: Goodell EW (1985). "Recycling of murein by Escherichia coli." J Bacteriol 163(1);305-10. PMID: 3891732

Jaeger05: Jaeger T, Arsic M, Mayer C (2005). "Scission of the lactyl ether bond of N-acetylmuramic acid by Escherichia coli "etherase"." J Biol Chem 280(34);30100-6. PMID: 15983044

Johnson13: Johnson JW, Fisher JF, Mobashery S (2013). "Bacterial cell-wall recycling." Ann N Y Acad Sci 1277;54-75. PMID: 23163477

MenginLecreulx96: Mengin-Lecreulx D, van Heijenoort J, Park JT (1996). "Identification of the mpl gene encoding UDP-N-acetylmuramate: L-alanyl-gamma-D-glutamyl-meso-diaminopimelate ligase in Escherichia coli and its role in recycling of cell wall peptidoglycan." J Bacteriol 178(18);5347-52. PMID: 8808921

Park08: Park JT, Uehara T (2008). "How bacteria consume their own exoskeletons (turnover and recycling of cell wall peptidoglycan)." Microbiol Mol Biol Rev 72(2);211-27, table of contents. PMID: 18535144

Uehara05: Uehara T, Suefuji K, Valbuena N, Meehan B, Donegan M, Park JT (2005). "Recycling of the anhydro-N-acetylmuramic acid derived from cell wall murein involves a two-step conversion to N-acetylglucosamine-phosphate." J Bacteriol 187(11);3643-9. PMID: 15901686

Uehara06: Uehara T, Suefuji K, Jaeger T, Mayer C, Park JT (2006). "MurQ Etherase is required by Escherichia coli in order to metabolize anhydro-N-acetylmuramic acid obtained either from the environment or from its own cell wall." J Bacteriol 188(4);1660-2. PMID: 16452451

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

Anantharaman03: Anantharaman V, Aravind L (2003). "Evolutionary history, structural features and biochemical diversity of the NlpC/P60 superfamily of enzymes." Genome Biol 2003;4(2);R11. PMID: 12620121

Aramini08: Aramini JM, Rossi P, Huang YJ, Zhao L, Jiang M, Maglaqui M, Xiao R, Locke J, Nair R, Rost B, Acton TB, Inouye M, Montelione GT (2008). "Solution NMR structure of the NlpC/P60 domain of lipoprotein Spr from Escherichia coli: structural evidence for a novel cysteine peptidase catalytic triad." Biochemistry 47(37);9715-7. PMID: 18715016

Barreteau08: Barreteau H, Kovac A, Boniface A, Sova M, Gobec S, Blanot D (2008). "Cytoplasmic steps of peptidoglycan biosynthesis." FEMS Microbiol Rev 32(2);168-207. PMID: 18266853

Baum05: Baum EZ, Crespo-Carbone SM, Foleno B, Peng S, Hilliard JJ, Abbanat D, Goldschmidt R, Bush K (2005). "Identification of a dithiazoline inhibitor of Escherichia coli L,D-carboxypeptidase A." Antimicrob Agents Chemother 49(11);4500-7. PMID: 16251288

Beck76: Beck BD, Park JT (1976). "Activity of three murein hydrolases during the cell division cycle of Escherichia coli K-12 as measured in toluene-treated cells." J Bacteriol 126(3);1250-60. PMID: 780345

Beck77: Beck BD, Park JT (1977). "Basis for the observed fluctuation of carboxypeptidase II activity during the cell cycle in BUG 6, a temperature-sensitive division mutant of Escherichia coli." J Bacteriol 130(3);1292-302. PMID: 405375

Bennett93: Bennett PM, Chopra I (1993). "Molecular basis of beta-lactamase induction in bacteria." Antimicrob Agents Chemother 37(2);153-8. PMID: 8452343

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Brokx04: Brokx SJ, Ellison M, Locke T, Bottorff D, Frost L, Weiner JH (2004). "Genome-wide analysis of lipoprotein expression in Escherichia coli MG1655." J Bacteriol 186(10);3254-8. PMID: 15126489

Brown99: Brown K, Pompeo F, Dixon S, Mengin-Lecreulx D, Cambillau C, Bourne Y (1999). "Crystal structure of the bifunctional N-acetylglucosamine 1-phosphate uridyltransferase from Escherichia coli: a paradigm for the related pyrophosphorylase superfamily." EMBO J 18(15);4096-107. PMID: 10428949

Burton06: Burton E, Gawande PV, Yakandawala N, LoVetri K, Zhanel GG, Romeo T, Friesen AD, Madhyastha S (2006). "Antibiofilm activity of GlmU enzyme inhibitors against catheter-associated uropathogens." Antimicrob Agents Chemother 50(5);1835-40. PMID: 16641457

Cheng00: Cheng Q, Li H, Merdek K, Park JT (2000). "Molecular characterization of the beta-N-acetylglucosaminidase of Escherichia coli and its role in cell wall recycling." J Bacteriol 2000;182(17);4836-40. PMID: 10940025

De96a: De Luca C, Lansing M, Crescenzi F, Martini I, Shen GJ, O'Regan M, Wong CH (1996). "Overexpression, one-step purification and characterization of UDP-glucose dehydrogenase and UDP-N-acetylglucosamine pyrophosphorylase." Bioorg Med Chem 4(1);131-41. PMID: 8689233

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

Dietz96: Dietz H, Pfeifle D, Wiedemann B (1996). "Location of N-acetylmuramyl-L-alanyl-D-glutamylmesodiaminopimelic acid, presumed signal molecule for beta-lactamase induction, in the bacterial cell." Antimicrob Agents Chemother 40(9);2173-7. PMID: 8878601

Dietz97: Dietz H, Pfeifle D, Wiedemann B (1997). "The signal molecule for beta-lactamase induction in Enterobacter cloacae is the anhydromuramyl-pentapeptide." Antimicrob Agents Chemother 41(10);2113-20. PMID: 9333034

Fang09: Fang J, Guan W, Cai L, Gu G, Liu X, Wang PG (2009). "Systematic study on the broad nucleotide triphosphate specificity of the pyrophosphorylase domain of the N-acetylglucosamine-1-phosphate uridyltransferase from Escherichia coli K12." Bioorg Med Chem Lett 19(22);6429-32. PMID: 19804974

Ferreira00: Ferreira FM, Mendoza-Hernandez G, Calcagno ML, Minauro F, Delboni LF, Oliva G (2000). "Crystallization and preliminary crystallographic analysis of N-acetylglucosamine 6-phosphate deacetylase from Escherichia coli." Acta Crystallogr D Biol Crystallogr 56(Pt 5);670-2. PMID: 10771446

Ferreira06: Ferreira FM, Mendoza-Hernandez G, Castaneda-Bueno M, Aparicio R, Fischer H, Calcagno ML, Oliva G (2006). "Structural analysis of N-acetylglucosamine-6-phosphate deacetylase apoenzyme from Escherichia coli." J Mol Biol 359(2);308-21. PMID: 16630633

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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 SRI International Pathway Tools version 18.5 on Mon Dec 22, 2014, biocyc12.