If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
Synonyms: 1,6-anhydro-N-acetylmuramic acid recycling, cell wall recycling
|Superclasses:||Degradation/Utilization/Assimilation → Secondary Metabolites Degradation → Sugar Derivatives Degradation|
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 22.214.171.124, N-acetylmuramoyl-L-alanine amidase (ampD), EC 126.96.36.199, 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 188.8.131.52, anhydro-N-acetylmuramic acid kinase (anmK) and then converted into N-acetyl-D-glucosamine 6-phosphate by EC 184.108.40.206, 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-acetyl-α-D-muramate, is one of the precursors for peptidoglycan biosynthesis.
The tripeptide L-alanyl-γ-D-glutamyl-meso-diaminopimelate, which is generated by EC 220.127.116.11, 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-acetyl-α-D-muramate, thereby substituting three amino acid ligases of the peptidoglycan de novo biosynthetic pathway [MenginLecreulx96a].
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].
MenginLecreulx96a: 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
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
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
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
Cheng00a: 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
De96b: 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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