Abstract:
Lipid intermediates I and II involved in the biosynthesis of bacterial peptidoglycan are the undecaprenyl pyrophosphoryl MurNAc-pentapeptide and undecaprenyl pyrophosphoryl GlcNAc-β-(1→4)-MurNAc-disaccharide-peptide, respectively. Membrane transferase MraY catalyzes the formation of lipid I whereas peripheral MurG transferase catalyzes the addition of N-acetylglucosamine onto lipid I to yield lipid II. These lipid intermediates often undergo additional modifications leading to complex pools. The glycan chains of peptidoglycan are assembled by polymerization of the GlcNAc-β-(1→4)-MurNAc-disaccharide-peptide unit of lipid II with formation of β-(1→4) linkages. Antibiotics such as glycopeptides and lantibiotics bind noncovalently with extracytoplasmically located lipid II and thereby lead to the arrest of peptidoglycan polymerization. Chemically or enzymatically synthesized lipid intermediates and analogues are now available in useful amounts for the study of the membrane steps of peptidoglycan biosynthesis, of the complexes formed with antibiotics, and of mechanisms of antibiotic resistance. Future work will require the development of convenient methods for the analysis of the lipid pools. Among the cellular aspects still poorly addressed, the elucidation of the mechanism of translocation of lipid II through the membrane remains an important challenging enigma.
Keywords
- Cytoplasmic Loop
- Glycan Chain
- Peptidoglycan Synthesis
- Bacterial Peptidoglycan
- Peptidoglycan Biosynthesis
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Barreteau H, Kovač A, Boniface A, Sova M, Gobec S, Blanot D (2008) Cytoplasmic steps of peptidoglycan synthesis. FEMS Microbiol Rev 32: 168–207.
Bauer R, Dicks LMT (2005) Mode of action of lipid II-targeting lantibiotics. Int J Food Microbiol 101: 201–216.
Bertsche U, Breukink E, Kast T, Vollmer W (2005) In vitro murein (peptidoglycan) synthesis by dimers of the bifunctional transglycosylase-transpeptidase PBP1B from Escherichia coli. J Biol Chem 280: 38096–38101.
Bouhss A, Crouvoisier M, Blanot D, Mengin-Lecreulx D (2004) Purification and characterization of the bacterial MraY translocase catalyzing the first membrane step of peptidoglycan biosynthesis. J Biol Chem 279: 29974–29980.
Bouhss A, Mengin-Lecreulx D, Le Beller D, van Heijenoort J (1999) Topological analysis of the MraY protein catalysing the first membrane step of peptidoglycan synthesis. Mol Microbiol 34: 576–585.
Bouhss A, Trunkfield AE, Bugg TDH, Mengin-Lecreulx D (2008) The biosynthesis of peptidoglycan lipid-linked intermediates. FEMS Microbiol Rev 32: 208–233.
Boyle DS, Donachie WD (1998) mraY is an essential gene for cell growth in Escherichia coli. J Bacteriol 180: 6429–6432.
Breukink EI, de Kruijff B (2006) Lipid II as a target for antibiotics. Nat Rev Drug Discov 4: 321–332.
Chatterjee C, Paul M, Xie L, van der Donk WA (2005) Biosynthesis and mode of action of lantibiotics. Chem Rev 105: 633–683.
Coutinho PM, Deleury E, Davies GJ, Henrissat B (2003) An evolving hierarchical family classification for glycosyltransferases. J Mol Biol 328: 307–317.
den Blaauwen T, de Pedro MA, Nguyen-Distèche M, Ayala JA (2008) Morphogenesis of rod-shaped sacculi. FEMS Microbiol Rev 32: 321–344.
Dini C (2005) MraY inhibitors as novel antibacterial agents. Curr Top Med Chem 5: 1221–1236.
Gale EF, Cundiffe E, Reynolds PE, Richmond MH, Warning MJ (1981) The Molecular Basis of Antibiotic Action. London: John Wiley and Sons.
Goffin C, Ghuysen J-M (1998) Multimodular penicillin-binding proteins: an enigmatic family of orthologs and paralogs. Microbiol Mol Biol Rev 62: 1079–1093.
Goffin C, Ghuysen J-M (2002) Biochemistry and comparative genomics of SxxK superfamily acyltransferases offer a clue to the mycobacterial paradox: presence of penicillin-susceptible target proteins versus lack of efficiency of penicillin as therapeutic agent. Microbiol Mol Biol Rev 66: 702–738.
Green DW (2002) The bacterial cell wall as a source of antibacterial targets. Expert Opin Ther Targets 6: 1–19.
Ha S, Walker D, Shi Y, Walker S (2000) The 1.9 Å crystal structure of Escherichia coli MurG, a membrane-associated glycosyltransferase involved in peptidoglycan biosynthesis. Protein Sci 9: 1045I–1052I.
Ikeda M, Wachi M, Jung HK, Ishino F, Matsuhashi M (1991) The Escherichia coli mraY gene encoding UDP-N-acetylmuramoyl-pentapeptide: undecaprenyl-phosphate phospho-N-acetylmuramoyl-pentapeptide transferase. J Bacteriol 173: 1021–1026.
Inoue A, Murata Y, Takahashi H, Tsuji N, Fujisaki S, Kato J (2008) Involement of an essential gene, mviN, in murein synthesis in Escherichia coli. J Bacteriol 190: 7298–7301.
Kahne D, Leimkuhler C, Lu W, Walsh C (2005) Glycopeptide and lipoglycopeptide antibiotics. Chem Rev 105: 425–448.
Kotnik M, Anderluh PS, Prezelj A (2007) Development of novel inhibitors targeting intracellular steps of peptidoglycan biosynthesis. Curr Pharma Design 13: 2283–2309.
Lovering AL, de Castro LH, Lim D, Strynadka NCJ (2007) Structural insight into the transglycosylation step of bacterial cell-wall biosynthesis. Science 315: 1402–1405.
Macheboeuf P, Contreras-Martel C, Job V, Dideberg O, Dessen A (2006) Penicillin binding proteins: key players in bacterial cell cycle and drug resistance processes. FEMS Microbiol Rev 30: 673–691.
Marraffini LA, Dedent AC, Schneewind O (2006) Sortases and the art of anchoring proteins to the envelopes of gram-positive bacteria. Microbiol Mol Biol Rev 70: 192–221.
Mengin-Lecreulx D, Texier L, Rousseau M, van Heijenoort J (1991) The murG gene of Escherichia coli codes for the UDP-N-acetylglucosamine:N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase involved in the membrane steps of peptidoglycan synthesis. J Bacteriol 173: 4625–4636.
Perlstein DL, Zhang Y, Wang T-S, Kahne DE, Walker S (2007) The direction of glycan chain elongation by peptidoglycan glycosyltransferases. J Am Chem Soc 129: 12674–12675.
Price NP, Momany FA (2005) Modeling bacterial UDP-hexNAc:polyprenol-P hexNAc-1-P transferases. Glycobiology 15: 29R–42R.
Ruiz N (2008) Bioinformatics identification of MurJ (MviN) as the peptidoglycan lipid II flippase in Escherichia coli. Proc Natl Acad Sci USA 105: 15553–15557.
Sauvage E, Kerff F, Terrak M, Ayala JA, Charlier P (2008) The penicillin-binding proteins: structure and role in peptidoglycan synthesis. FEMS Microbiol Rev 32: 234–258.
Tiyanont K, Doan T, Lazarus MB, Fang X, Rudner DZ, Walker S (2006) Imaging peptidoglycan biosynthesis in Bacillus subtilis with fluorescent antibiotics. Proc Natl Acad Sci USA 103: 11033–11038.
Ünligil UM, Rini JM (2000) Glycosyltransferase structure and mechanism. Curr Opin Struct Biol 10: 510–517.
van Dam V, Sijbrandi R, Kol M, Swiezewska E, de Kruijffl B, Breukink E (2007) Transmembrane transport of peptidoglycan precursors across model and bacterial membranes. Mol Microbiol 64: 1105–1114.
van Heijenoort J (2001a) Formation of the glycan chains in the synthesis of bacterial peptidoglycan. Glycobiology 11: 25R–36R.
van Heijenoort J (2001b) Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat Prod Rep 18: 503–519.
van Heijenoort J (2007) Lipid intermediates in the biosynthesis of bacterial peptidoglycan. Microbiol Mol Bio Rev 71: 620–635.
Vollmer W, Blanot D, de Pedro MA (2008) Peptidoglycan structure and architecture. FEMS Microbiol Rev 32: 149–167.
Walker S, Chen L, Hu Y, Rew Y, Shin D, Boger DL (2005) Chemistry and biology of ramoplanin: a lipoglycodepsipeptide with potent antibiotic activity. Chem Rev 105: 449–475.
Welzel P (2005) Syntheses around the transglycosylation step in peptidoglycan biosynthesis. Chem Rev 105: 4610–4660.
Yuan Y, Barrett D, Zhang Y, Kahne D, Sliz P, Walker S (2007) Crystal structure of a peptidoglycan glycosyltransferase suggests a model for processive glycan chain synthesis. Proc Natl Acad Sci USA 104: 5348–5353.
Zapun AT, Vernet T, Pinho MG (2008) The different shapes of cocci. FEMS Microbiol Rev 32: 345–360.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer-Verlag Berlin Heidelberg
About this entry
Cite this entry
van Heijenoort, J. (2010). Lipid Intermediates in Bacterial Peptidoglycan Biosynthesis. In: Timmis, K.N. (eds) Handbook of Hydrocarbon and Lipid Microbiology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-77587-4_31
Download citation
DOI: https://doi.org/10.1007/978-3-540-77587-4_31
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-77584-3
Online ISBN: 978-3-540-77587-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences