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Pathway Description
Peptidoglycan Biosynthesis I
Pseudomonas aeruginosa
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2019-08-12
Last Updated: 2019-09-15
Peptidoglycan is a net-like polymer which surrounds the cytoplasmic membrane of most bacteria and functions to maintain cell shape and prevent rupture due to the internal turgor. In E. coli K-12, the peptidoglycan consists of glycan strands of alternating subunits of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) which are cross-linked by short peptides. The pathway for constructing this net involves two cell compartments: cytoplasm and periplasmic space.
The pathway starts with a beta-D-fructofuranose going through a mannose PTS permease, phosphorylating the compound and producing a beta-D-fructofuranose 6 phosphate. This compound can be obtained from the glycolysis and pyruvate dehydrogenase or from an isomerization reaction of Beta-D-glucose 6-phosphate through a glucose-6-phosphate isomerase. The compound Beta-D-fructofuranose 6 phosphate and L-Glutamine react with a glucosamine fructose-6-phosphate aminotransferase, thus producing a glucosamine 6-phosphate and a l-glutamic acid. The glucosamine 6-phosphate interacts with phosphoglucosamine mutase in a reversible reaction producing glucosamine-1P. Glucosamine-1p and acetyl-CoA undergo acetylation through a bifunctional protein glmU releasing Coa and a hydrogen ion and producing a N-acetyl-glucosamine 1-phosphate. Glmu, being a bifunctional protein catalyzes the interaction of N-acetyl-glucosamine 1-phosphate, hydrogen ion and UTP into UDP-N-acetylglucosamine and pyrophosphate. UDP-N-acetylglucosamine then interacts with phosphoenolpyruvic acid and a UDP-N acetylglucosamine 1- carboxyvinyltransferase releasing a phosphate and the compound UDP-N-acetyl-alpha-D-glucosamine-enolpyruvate.
The latter undergoes a NADPH dependent reduction producing a UDP-N-acetyl-alpha-D-muramate catalyzed by a UDP-N-acetylenolpyruvoylglucosamine reductase. UDP-N-acetyl-alpha-D-muramate and L-alanine react in an ATP-mediated ligation through a UDP-N-acetylmuramate-alanine ligase releasing an ADP, hydrogen ion, phosphate and a UDP-N-acetylmuramoyl-L-alanine. Next, UDP-N-acetylmuramoylalanine-D-glutamate ligase catalyzes an ATP, D-glutamic acid and UDP-N-acetylmuramoyl-L-alanine releasing ADP, phosphate and UDP-N-acetylmuramoyl-L-alanyl-D-glutamate. The latter product then interacts with meso-diaminopimelate in an ATP mediated ligation through a UDP-N-acetylmuramoylalanine-D-glutamate-2,6-diaminopimelate ligase resulting in ADP, phosphate, hydrogen ion and UDP-N-Acetylmuramoyl-L-alanyl-D-gamma-glutamyl-meso-2,6-diaminopimelate. This compound in turn with D-alanyl-D-alanine react in an ATP-mediated ligation through UDP-N-Acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase to produce UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gama-D-glutamyl-meso-2,6-diaminopimeloyl-Dalanyl-D-alanine and hydrogen ion, ADP, phosphate. UDP-N-acetyl-alpha-D-muramoyl-L-alanyl-gama-D-glutamyl-meso-2,6-diaminopimeloyl-Dalanyl-D-alanine interacts with di-trans,octa-cis-undecaprenyl phosphate through a phospho-N-acetylmuramoyl-pentapeptide-transferase, resulting in UMP and Undecaprenyl-diphospho-N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine which in turn reacts with a UDP-N-acetylglucosamine through a N-acetylglucosaminyl transferase to produce a hydrogen, UDP and ditrans,octacis-undecaprenyldiphospho-N-acetyl-(N-acetylglucosaminyl)muramoyl-L-alanyl-gamma-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine. This compound ends the cytoplasmic part of the pathway. ditrans,octacis-undecaprenyldiphospho-N-acetyl-(N-acetylglucosaminyl)muramoyl-L-alanyl-gamma-D-glutamyl-meso-2,6-diaminopimeloyl-D-alanyl-D-alanine is transported through a lipi II flippase. Once in the periplasmic space, the compound reacts with a penicillin binding protein 1A prodducing a peptidoglycan dimer, a hydrogen ion, and UDP. The peptidoglycan dimer then reacts with a penicillin binding protein 1B producing a peptidoglycan with D,D, cross-links and a D-alanine.
References
Peptidoglycan Biosynthesis I References
Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, Brinkman FS, Hufnagle WO, Kowalik DJ, Lagrou M, Garber RL, Goltry L, Tolentino E, Westbrock-Wadman S, Yuan Y, Brody LL, Coulter SN, Folger KR, Kas A, Larbig K, Lim R, Smith K, Spencer D, Wong GK, Wu Z, Paulsen IT, Reizer J, Saier MH, Hancock RE, Lory S, Olson MV: Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature. 2000 Aug 31;406(6799):959-64. doi: 10.1038/35023079.
Pubmed: 10984043
El Zoeiby A, Sanschagrin F, Lamoureux J, Darveau A, Levesque RC: Cloning, over-expression and purification of Pseudomonas aeruginosa murC encoding uridine diphosphate N-acetylmuramate: L-alanine ligase. FEMS Microbiol Lett. 2000 Feb 15;183(2):281-8. doi: 10.1111/j.1574-6968.2000.tb08972.x.
Pubmed: 10675598
Azzolina BA, Yuan X, Anderson MS, El-Sherbeini M: The cell wall and cell division gene cluster in the Mra operon of Pseudomonas aeruginosa: cloning, production, and purification of active enzymes. Protein Expr Purif. 2001 Apr;21(3):393-400. doi: 10.1006/prep.2001.1390.
Pubmed: 11281713
Liao X, Hancock RE: Cloning and characterization of the Pseudomonas aeruginosa pbpB gene encoding penicillin-binding protein 3. Antimicrob Agents Chemother. 1995 Aug;39(8):1871-4. doi: 10.1128/aac.39.8.1871.
Pubmed: 7486937
Martin PR, Hobbs M, Free PD, Jeske Y, Mattick JS: Characterization of pilQ, a new gene required for the biogenesis of type 4 fimbriae in Pseudomonas aeruginosa. Mol Microbiol. 1993 Aug;9(4):857-68. doi: 10.1111/j.1365-2958.1993.tb01744.x.
Pubmed: 7901733
de Leon SR, Daniels K, Clarke AJ: Production and purification of the penicillin-binding protein 3 from Pseudomonas aeruginosa. Protein Expr Purif. 2010 Oct;73(2):177-83. doi: 10.1016/j.pep.2010.05.005. Epub 2010 May 16.
Pubmed: 20580675
Liao X, Hancock RE: Identification of a penicillin-binding protein 3 homolog, PBP3x, in Pseudomonas aeruginosa: gene cloning and growth phase-dependent expression. J Bacteriol. 1997 Mar;179(5):1490-6. doi: 10.1128/jb.179.5.1490-1496.1997.
Pubmed: 9045804
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000924
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