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Lipid Intermediates in Bacterial Peptidoglycan Biosynthesis

  • Hélène Barreteau
  • Didier Blanot
  • Dominique Mengin-Lecreulx
  • Thierry TouzéEmail author
Reference work entry
Part of the Handbook of Hydrocarbon and Lipid Microbiology book series (HHLM)

Abstract

Peptidoglycan constitutes one of the major “Achilles heels” of bacteria because it is an essential component for cell integrity, and its metabolism is the target for a great number of antibacterials of different natures, e.g., antibiotics such as β-lactams and vancomycin, host immune system antimicrobial peptides, and bacteriocins. Peptidoglycan synthesis requires the translocation, across the plasma membrane, of the polymer building block, a disaccharide-pentapeptide. This event is performed via the attachment of the subunit to a lipid carrier, undecaprenyl-phosphate. Lipid intermediates called lipids I and II are generated through the sequential transfer of N-acetylmuramoyl-pentapeptide and N-acetylglucosamine moieties from nucleotide precursors to the lipid carrier by MraY and MurG transglycosylases, respectively. The last membrane intermediate, lipid II (undecaprenyl-pyrophosphate-N-acetylmuramoyl(-pentapeptide)-N-acetylglucosamine), can be further enzymatically modified through the addition of functional groups, amino acids, or peptides, before being flipped towards the outer leaflet of the plasma membrane where the final transfer of the peptidoglycan subunits to the growing polymer is catalyzed by penicillin-binding proteins. The integral membrane proteins FtsW, MurJ, and AmJ are thought to play a major role in the translocation process; however, the exact mechanism and the role of these molecular determinants is yet to be established. The lipid carrier is generated via a pathway involving two steps, first a polymerization reaction of isopentenyl-pyrophosphate catalyzed by the essential cytosoluble UppS enzyme, yielding undecaprenyl-pyrophosphate, followed by a dephosphorylation step ensured by a yet unknown enzyme. At each final transfer of a subunit to the elongating peptidoglycan, the lipid carrier is released in the pyrophosphate form, which is recycled to guarantee the high rate of polymer synthesis. Several integral membrane undecaprenyl-pyrophosphate phosphatases, from two distinct protein families and having their active site facing the extracytoplasmic side, have been identified, BacA and PAP2 enzymes. These enzymes can readily dephosphorylate the released lipid carrier precursor. Thereafter, the lipid is flipped back to the inner side of the membrane, by a yet unknown mechanism, in order to be reused as a glycan acceptor for a new round of peptidoglycan polymerization.

References

  1. Al-Dabbagh B, Henry X, El Ghachi M, Auger G, Blanot D, Parquet C, Mengin-Lecreulx D, Bouhss A (2008) Active site mapping of MraY, a member of the polyprenyl-phosphate N-acetylhexosamine 1-phosphate transferase superfamily, catalyzing the first membrane step of peptidoglycan biosynthesis. Biochemistry 47:8919–8928PubMedCrossRefGoogle Scholar
  2. Al-Dabbagh B, Olatunji S, Crouvoisier M, El Ghachi M, Blanot D, Mengin-Lecreulx D, Bouhss A (2016) Catalytic mechanism of MraY and WecA, two paralogues of the polyprenyl-phosphate N-acetylhexosamine 1-phosphate transferase superfamily. Biochimie 127:249–257PubMedCrossRefGoogle Scholar
  3. Barreteau H, Kovač A, Boniface A, Sova M, Gobec S, Blanot D (2008) Cytoplasmic steps of peptidoglycan biosynthesis. FEMS Microbiol Rev 32:168–207PubMedCrossRefGoogle Scholar
  4. Barreteau H, Bouhss A, Fourgeaud M, Mainardi JL, Touzé T, Gérard F, Blanot D, Arthur M, Mengin-Lecreulx D (2009) Human- and plant-pathogenic Pseudomonas species produce bacteriocins exhibiting colicin M-like hydrolase activity towards peptidoglycan precursors. J Bacteriol 191:3657–3664PubMedPubMedCentralCrossRefGoogle Scholar
  5. Bellais S, Arthur M, Dubost L, Hugonnet JE, Gutmann L, van Heijenoort J, Legrand R, Brouard JP, Rice L, Mainardi JL (2006) Aslfm, the d-aspartate ligase responsible for the addition of d-aspartic acid onto the peptidoglycan precursor of Enterococcus faecium. J Biol Chem 281:11586–11594PubMedCrossRefPubMedCentralGoogle Scholar
  6. den Blaauwen T, de Pedro MA, Nguyen-Distèche M, Ayala JA (2008) Morphogenesis of rod-shaped sacculi. FEMS Microbiol Rev 32:321–344CrossRefGoogle Scholar
  7. 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 34:576–585PubMedCrossRefPubMedCentralGoogle Scholar
  8. 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 279:29974–29980PubMedCrossRefGoogle Scholar
  9. Bouhss A, Trunkfield AE, Bugg TD, Mengin-Lecreulx D (2008) The biosynthesis of peptidoglycan lipid-linked intermediates. FEMS Microbiol Rev 32:208–233PubMedCrossRefGoogle Scholar
  10. Boyle DS, Khattar MM, Addinall SG, Lutkenhaus J, Donachie WD (1997) ftsW is an essential cell-division gene in Escherichia coli. Mol Microbiol 24:1263–1273PubMedCrossRefGoogle Scholar
  11. Bradshaw WJ, Davies AH, Chambers CJ, Roberts AK, Shone CC, Acharya KR (2015) Molecular features of the sortase enzyme family. FEBS J 282:2097–2114PubMedCrossRefGoogle Scholar
  12. Braun V, Rehn K (1969) Chemical characterization, spatial distribution and function of a lipoprotein (murein-lipoprotein) of the Escherichia coli cell wall. The specific effect of trypsin on the membrane structure. Eur J Biochem 10:426–438PubMedCrossRefGoogle Scholar
  13. Breukink E, de Kruijff B (2006) Lipid II as a target for antibiotics. Nat Rev Drug Discov 5:321–332PubMedCrossRefGoogle Scholar
  14. Brötz H, Bierbaum G, Leopold K, Reynolds PE, Sahl HG (1998) The lantibiotic mersacidin inhibits peptidoglycan synthesis by targeting lipid II. Antimicrob Agents Chemother 42:154–160PubMedPubMedCentralCrossRefGoogle Scholar
  15. Brown K, Vial SC, Dedi N, Westcott J, Scally S, Bugg TD, Charlton PA, Cheetham GM (2013) Crystal structure of the Pseudomonas aeruginosa MurG:UDP-GlcNAc substrate complex. Protein Pept Lett 20:1002–1008PubMedCrossRefGoogle Scholar
  16. Bugg TD, Braddick D, Dowson CG, Roper DI (2011) Bacterial cell wall assembly: still an attractive antibacterial target. Trends Biotechnol 29:167–173PubMedCrossRefGoogle Scholar
  17. Bugg TD, Rodolis MT, Mihalyi A, Jamshidi S (2016) Inhibition of phospho-MurNAc-pentapeptide translocase (MraY) by nucleoside natural product antibiotics, bacteriophage ΦX174 lysis protein E, and cationic antibacterial peptides. Bioorg Med Chem 24:6340–6347CrossRefGoogle Scholar
  18. Bupp K, van Heijenoort J (1993) The final step of peptidoglycan subunit assembly in Escherichia coli occurs in the cytoplasm. J Bacteriol 175:1841–1843PubMedPubMedCentralCrossRefGoogle Scholar
  19. Cascales E, Buchanan SK, Duché D, Kleanthous C, Lloubès R, Postle K, Riley M, Slatin S, Cavard D (2007) Colicin biology. Microbiol Mol Biol Rev 71:158–229PubMedPubMedCentralCrossRefGoogle Scholar
  20. Chang HY, Chou CC, Hsu MF, Wang AH (2014) Proposed carrier lipid-binding site of undecaprenyl pyrophosphate phosphatase from Escherichia coli. J Biol Chem 289:18719–18735PubMedPubMedCentralCrossRefGoogle Scholar
  21. Chen L, Men H, Ha S, Ye XY, Brunner L, Hu Y, Walker S (2002) Intrinsic lipid preferences and kinetic mechanism of Escherichia coli MurG. Biochemistry 41:6824–6833PubMedCrossRefGoogle Scholar
  22. Chung BC, Zhao J, Gillespie RA, Kwon DY, Guan Z, Hong J, Zhou P, Lee SY (2013) Crystal structure of MraY, an essential membrane enzyme for bacterial cell wall synthesis. Science 341:1012–1016PubMedPubMedCentralCrossRefGoogle Scholar
  23. Chung BC, Mashalidis EH, Tanino T, Kim M, Matsuda A, Hong J, Ichikawa S, Lee SY (2016) Structural insights into inhibition of lipid I production in bacterial cell wall synthesis. Nature 533:557–560PubMedPubMedCentralCrossRefGoogle Scholar
  24. Crouvoisier M, Mengin-Lecreulx D, van Heijenoort J (1999) UDP-N-acetylglucosamine:N-acetylmuramoyl-(pentapeptide) pyrophosphoryl undecaprenol N-acetylglucosamine transferase from Escherichia coli: overproduction, solubilization, and purification. FEBS Lett 449:289–292PubMedCrossRefGoogle Scholar
  25. Crouvoisier M, Auger G, Blanot D, Mengin-Lecreulx D (2007) Role of the amino acid invariants in the active site of MurG as evaluated by site-directed mutagenesis. Biochimie 89:1498–1508PubMedCrossRefGoogle Scholar
  26. Dillon DA, Wu WI, Riedel B, Wissing JB, Dowhan W, Carman GM (1996) The Escherichia coli pgpB gene encodes for a diacylglycerol pyrophosphate phosphatase activity. J Biol Chem 271:30548–30553PubMedCrossRefGoogle Scholar
  27. Dini C (2005) MraY inhibitors as novel antibacterial agents. Curr Top Med Chem 5:1221–1236PubMedCrossRefGoogle Scholar
  28. Dramsi S, Magnet S, Davison S, Arthur M (2008) Covalent attachment of proteins to peptidoglycan. FEMS Microbiol Rev 32:307–320PubMedCrossRefGoogle Scholar
  29. El Ghachi M, Bouhss A, Blanot D, Mengin-Lecreulx D (2004) The bacA gene of Escherichia coli encodes an undecaprenyl pyrophosphate phosphatase activity. J Biol Chem 279:30106–30113PubMedCrossRefGoogle Scholar
  30. El Ghachi M, Derbise A, Bouhss A, Mengin-Lecreulx D (2005) Identification of multiple genes encoding membrane proteins with undecaprenyl pyrophosphate phosphatase (UppP) activity in Escherichia coli. J Biol Chem 280:18689–18695PubMedCrossRefGoogle Scholar
  31. El Ghachi M, Bouhss A, Barreteau H, Touzé T, Auger G, Blanot D, Mengin-Lecreulx D (2006) Colicin M exerts its bacteriolytic effect via enzymatic degradation of undecaprenyl phosphate-linked peptidoglycan precursors. J Biol Chem 281:22761–22772PubMedCrossRefGoogle Scholar
  32. Fan J, Jiang D, Zhao Y, Liu J, Zhang XC (2014) Crystal structure of lipid phosphatase Escherichia coli phosphatidylglycerophosphate phosphatase B. Proc Natl Acad Sci U S A 111:7636–7640PubMedPubMedCentralCrossRefGoogle Scholar
  33. Fay A, Dworkin J (2009) Bacillus subtilis homologs of MviN (MurJ), the putative Escherichia coli lipid II flippase, are not essential for growth. J Bacteriol 191:6020–6028PubMedPubMedCentralCrossRefGoogle Scholar
  34. Figueiredo TA, Sobral RG, Ludovice AM, Almeida JM, Bui NK, Vollmer W, de Lencastre H, Tomasz A (2012) Identification of genetic determinants and enzymes involved with the amidation of glutamic acid residues in the peptidoglycan of Staphylococcus aureus. PLoS Pathog 8:e1002508PubMedPubMedCentralCrossRefGoogle Scholar
  35. Fraipont C, Alexeeva S, Wolf B, van der Ploeg R, Schloesser M, den Blaauwen T, Nguyen-Distèche M (2011) The integral membrane FtsW protein and peptidoglycan synthase PBP3 form a subcomplex in Escherichia coli. Microbiology 157:251–259PubMedCrossRefGoogle Scholar
  36. Fujihashi M, Zhang YW, Higuchi Y, Li XY, Koyama T, Miki K (2001) Crystal structure of cis-prenyl chain elongating enzyme, undecaprenyl diphosphate synthase. Proc Natl Acad Sci U S A 98:4337–4342PubMedPubMedCentralCrossRefGoogle Scholar
  37. Grinter R, Milner J, Walker D (2012) Ferredoxin containing bacteriocins suggest a novel mechanism of iron uptake in Pectobacterium spp. PLoS ONE 7:e33033PubMedPubMedCentralCrossRefGoogle Scholar
  38. Guo RT, Ko TP, Chen AP, Kuo CJ, Wang AH, Liang PH (2005) Crystal structures of undecaprenyl pyrophosphate synthase in complex with magnesium, isopentenyl pyrophosphate, and farnesyl thiopyrophosphate: roles of the metal ion and conserved residues in catalysis. J Biol Chem 280:20762–20774PubMedCrossRefGoogle Scholar
  39. Ha S, Chang E, Lo MC, Men H, Park P, Ge M, Walker S (1999) The kinetic characterization of Escherichia coli MurG using synthetic substrate analogues. J Am Chem Soc 121:8415–8426CrossRefGoogle Scholar
  40. 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 9:1045–1052PubMedPubMedCentralCrossRefGoogle Scholar
  41. Hamburger JB, Hoertz AJ, Lee A, Senturia RJ, McCafferty DG, Loll PJ (2009) A crystal structure of a dimer of the antibiotic ramoplanin illustrates membrane positioning and a potential lipid II docking interface. Proc Natl Acad Sci U S A 106:13759–13764PubMedPubMedCentralCrossRefGoogle Scholar
  42. van Heijenoort J (2010) Lipid intermediates in bacterial peptidoglycan biosynthesis. In: Timmis KN (ed) Handbook of hydrocarbon and lipid microbiology, 1st edn. Springer, Berlin/Heidelberg, pp 435–444CrossRefGoogle Scholar
  43. Henrich E, Ma Y, Engels I, Münch D, Otten C, Schneider T, Henrichfreise B, Sahl HG, Dötsch V, Bernhard F (2016) Lipid requirements for the enzymatic activity of MraY translocases and in vitro reconstitution of the lipid II synthesis pathway. J Biol Chem 291:2535–2546PubMedCrossRefGoogle Scholar
  44. Herrera CM, Hankins JV, Trent MS (2010) Activation of PmrA inhibits LpxT-dependent phosphorylation of lipid A promoting resistance to antimicrobial peptides. Mol Microbiol 76:1444–1460PubMedPubMedCentralCrossRefGoogle Scholar
  45. Hsu ST, Breukink E, Bierbaum G, Sahl HG, de Kruijff B, Kaptein R, van Nuland NA, Bonvin AM (2003) NMR study of mersacidin and lipid II interaction in dodecylphosphocholine micelles: conformational changes are a key to antimicrobial activity. J Biol Chem 278:13110–13117PubMedCrossRefGoogle Scholar
  46. Hu Y, Chen L, Ha S, Gross B, Falcone B, Walker D, Mokhtarzadeh M, Walker S (2003) Crystal structure of the MurG:UDP-GlcNAc complex reveals common structural principles of a superfamily of glycosyltransferases. Proc Natl Acad Sci USA 100:845–849PubMedCrossRefGoogle Scholar
  47. Hu Y, Helm JS, Chen L, Ginsberg C, Gross B, Kraybill B, Tiyanont K, Fang X, Wu T, Walker S (2004) Identification of selective inhibitors for the glycosyltransferase MurG via high-throughput screening. Chem Biol 11:703–711PubMedCrossRefPubMedCentralGoogle Scholar
  48. Hvorup RN, Winnen B, Chang AB, Jiang Y, Zhou XF, Saier MH Jr (2003) The multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) exporter superfamily. Eur J Biochem 270:799–813PubMedCrossRefGoogle Scholar
  49. Inoue A, Murata Y, Takahashi H, Tsuji N, Fujisaki S, Kato J (2008) Involvement of an essential gene, mviN, in murein synthesis in Escherichia coli. J Bacteriol 190:7298–7301PubMedPubMedCentralCrossRefGoogle Scholar
  50. Ishikawa K, Mihara Y, Gondoh K, Suzuki E, Asano Y (2000) X-ray structures of a novel acid phosphatase from Escherichia blattae and its complex with the transition-state analog molybdate. EMBO J 19:2412–2423PubMedPubMedCentralCrossRefGoogle Scholar
  51. Islam ST, Lam JS (2013) Wzx flippase-mediated membrane translocation of sugar polymer precursors in bacteria. Environ Microbiol 15:1001–1015PubMedCrossRefGoogle Scholar
  52. Jukič M, Rožman K, Gobec S (2016) Recent advances in the development of undecaprenyl pyrophosphate synthase inhibitors as potential antibacterials. Curr Med Chem 23:464–482PubMedCrossRefGoogle Scholar
  53. Kato A, Chen HD, Latifi T, Groisman EA (2012) Reciprocal control between a bacterium’s regulatory system and the modification status of its lipopolysaccharide. Mol Cell 47:897–908PubMedPubMedCentralCrossRefGoogle Scholar
  54. Kleijn LH, Oppedijk SF, ‘t Hart P, van Harten RM, Martin-Visscher LA, Kemmink J, Breukink E, Martin NI (2016) Total synthesis of laspartomycin C and characterization of its antibacterial mechanism of action. J Med Chem 59:3569–3574PubMedCrossRefGoogle Scholar
  55. Ko TP, Chen YK, Robinson H, Tsai PC, Gao YG, Chen AP, Wang AH, Liang PH (2001) Mechanism of product chain length determination and the role of a flexible loop in Escherichia coli undecaprenyl-pyrophosphate synthase catalysis. J Biol Chem 276:47474–47482PubMedCrossRefGoogle Scholar
  56. Levefaudes M, Patin D, de Sousa-d’Auria C, Chami M, Blanot D, Hervé M, Arthur M, Houssin C, Mengin-Lecreulx D (2015) Diaminopimelic acid amidation in Corynebacteriales: new insights into the role of LtsA in peptidoglycan modification. J Biol Chem 290:13079–13094PubMedPubMedCentralCrossRefGoogle Scholar
  57. Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Mueller A, Schaberle TF, Hughes DE, Epstein S, Jones M, Lazarides L, Steadman VA, Cohen DR, Felix CR, Fetterman KA, Millett WP, Nitti AG, Zullo AM, Chen C, Lewis K (2015) A new antibiotic kills pathogens without detectable resistance. Nature 517:455–459PubMedCrossRefGoogle Scholar
  58. Liu Y, Rodrigues JP, Bonvin AM, Zaal EA, Berkers CR, Heger M, Gawarecka K, Swiezewska E, Breukink E, Egmond MR (2016) New insight into the catalytic mechanism of bacterial MraY from enzyme kinetics and docking studies. J Biol Chem 291:15057–15068PubMedCrossRefGoogle Scholar
  59. Lovering AL, Safadi SS, Strynadka NC (2012) Structural perspective of peptidoglycan biosynthesis and assembly. Annu Rev Biochem 81:451–478PubMedCrossRefGoogle Scholar
  60. Magnet S, Arbeloa A, Mainardi JL, Hugonnet JE, Fourgeaud M, Dubost L, Marie A, Delfosse V, Mayer C, Rice LB, Arthur M (2007) Specificity of l,d-transpeptidases from Gram-positive bacteria producing different peptidoglycan chemotypes. J Biol Chem 282:13151–13159PubMedCrossRefGoogle Scholar
  61. Mainardi JL, Villet R, Bugg TD, Mayer C, Arthur M (2008) Evolution of peptidoglycan biosynthesis under the selective pressure of antibiotics in Gram-positive bacteria. FEMS Microbiol Rev 32:386–408PubMedCrossRefGoogle Scholar
  62. Manat G, Roure S, Auger R, Bouhss A, Barreteau H, Mengin-Lecreulx D, Touzé T (2014) Deciphering the metabolism of undecaprenyl-phosphate: the bacterial cell-wall unit carrier at the membrane frontier. Microb Drug Resist 20:199–214PubMedPubMedCentralCrossRefGoogle Scholar
  63. Manat G, El Ghachi M, Auger R, Baouche K, Olatunji S, Kerff F, Touzé T, Mengin-Lecreulx D, Bouhss A (2015) Membrane topology and biochemical characterization of the Escherichia coli BacA undecaprenyl-pyrophosphate phosphatase. PLoS ONE 10:e0142870PubMedPubMedCentralCrossRefGoogle Scholar
  64. Mann PA, Müller A, Xiao L, Pereira PM, Yang C, Ho Lee S, Wang H, Trzeciak J, Schneeweis J, Dos Santos MM, Murgolo N, She X, Gill C, Balibar CJ, Labroli M, Su J, Flattery A, Sherborne B, Maier R, Tan CM, Black T, Onder K, Kargman S, Monsma FJ Jr, Pinho MG, Schneider T, Roemer T (2013) Murgocil is a highly bioactive staphylococcal-specific inhibitor of the peptidoglycan glycosyltransferase enzyme MurG. ACS Chem Biol 8:2442–2451PubMedCrossRefGoogle Scholar
  65. Meeske AJ, Sham LT, Kimsey H, Koo BM, Gross CA, Bernhardt TG, Rudner DZ (2015) MurJ and a novel lipid II flippase are required for cell wall biogenesis in Bacillus subtilis. Proc Natl Acad Sci USA 112:6437–6442PubMedCrossRefGoogle Scholar
  66. Mohammadi T, van Dam V, Sijbrandi R, Vernet T, Zapun A, Bouhss A, Diepeveen-de Bruin M, Nguyen-Distèche M, de Kruijff B, Breukink E (2011) Identification of FtsW as a transporter of lipid-linked cell wall precursors across the membrane. EMBO J 30:1425–1432PubMedPubMedCentralCrossRefGoogle Scholar
  67. Münch D, Roemer T, Lee SH, Engeser M, Sahl HG, Schneider T (2012) Identification and in vitro analysis of the GatD/MurT enzyme-complex catalyzing lipid II amidation in Staphylococcus aureus. PLoS Pathog 8:e1002509PubMedPubMedCentralCrossRefGoogle Scholar
  68. Perkins HR (1969) Specificity of combination between mucopeptide precursors and vancomycin or ristocetin. Biochem J 111:195–205PubMedPubMedCentralCrossRefGoogle Scholar
  69. Price NP, Momany FA (2005) Modeling bacterial UDP-HexNAc: polyprenol-P HexNAc-1-P transferases. Glycobiology 15:29R–42RPubMedCrossRefGoogle Scholar
  70. Ruiz N (2008) Bioinformatics identification of MurJ (MviN) as the peptidoglycan lipid II flippase in Escherichia coli. Proc Natl Acad Sci USA 105:15553–15557PubMedCrossRefPubMedCentralGoogle Scholar
  71. Ruiz N (2016) Filling holes in peptidoglycan biogenesis of Escherichia coli. Curr Opin Microbiol 34:1–6PubMedPubMedCentralCrossRefGoogle Scholar
  72. Sauvage E, Kerff F, Terrak M, Ayala JA, Charlier P (2008) The penicillin-binding proteins: structure and role in peptidoglycan biosynthesis. FEMS Microbiol Rev 32:234–258PubMedCrossRefGoogle Scholar
  73. Schneider T, Senn MM, Berger-Bächi B, Tossi A, Sahl HG, Wiedemann I (2004) In vitro assembly of a complete, pentaglycine interpeptide bridge containing cell wall precursor (lipid II-Gly5) of Staphylococcus aureus. Mol Microbiol 53:675–685PubMedCrossRefGoogle Scholar
  74. Schneider T, Gries K, Josten M, Wiedemann I, Pelzer S, Labischinski H, Sahl HG (2009) The lipopeptide antibiotic friulimicin B inhibits cell wall biosynthesis through complex formation with bactoprenol phosphate. Antimicrob Agents Chemother 53:1610–1618PubMedPubMedCentralCrossRefGoogle Scholar
  75. Sham LT, Butler EK, Lebar MD, Kahne D, Bernhardt TG, Ruiz N (2014) Bacterial cell wall. MurJ is the flippase of lipid-linked precursors for peptidoglycan biogenesis. Science 345:220–222PubMedPubMedCentralCrossRefGoogle Scholar
  76. Siewert G, Strominger JL (1967) Bacitracin: an inhibitor of the dephosphorylation of lipid pyrophosphate, an intermediate in the biosynthesis of the peptidoglycan of bacterial cell walls. Proc Natl Acad Sci USA 57:767–773PubMedCrossRefGoogle Scholar
  77. Sigal YJ, McDermott MI, Morris AJ (2005) Integral membrane lipid phosphatases/phosphotransferases: common structure and diverse functions. Biochem J 387:281–293PubMedPubMedCentralCrossRefGoogle Scholar
  78. Stone KJ, Strominger JL (1971) Mechanism of action of bacitracin: complexation with metal ion and C55-isoprenyl pyrophosphate. Proc Natl Acad Sci USA 68:3223–3227PubMedCrossRefGoogle Scholar
  79. Tanino T, Al-Dabbagh B, Mengin-Lecreulx D, Bouhss A, Oyama H, Ichikawa S, Matsuda A (2011) Mechanistic analysis of muraymycin analogues: a guide to the design of MraY inhibitors. J Med Chem 54:8421–8439PubMedCrossRefGoogle Scholar
  80. Tatar LD, Marolda CL, Polischuk AN, van Leeuwen D, Valvano MA (2007) An Escherichia coli undecaprenyl-pyrophosphate phosphatase implicated in undecaprenyl phosphate recycling. Microbiology 153:2518–2529PubMedCrossRefGoogle Scholar
  81. Teng KH, Liang PH (2012) Undecaprenyl diphosphate synthase, a cis-prenyltransferase synthesizing lipid carrier for bacterial cell wall biosynthesis. Mol Membr Biol 29:267–273PubMedCrossRefGoogle Scholar
  82. Teo AC, Roper DI (2015) Core steps of membrane-bound peptidoglycan biosynthesis: recent advances, insight and opportunities. Antibiotics (Basel) 4:495–520CrossRefGoogle Scholar
  83. Touzé T, Blanot D, Mengin-Lecreulx D (2008a) Substrate specificity and membrane topology of Escherichia coli PgpB, an undecaprenyl pyrophosphate phosphatase. J Biol Chem 283:16573–16583PubMedCrossRefGoogle Scholar
  84. Touzé T, Tran AX, Hankins JV, Mengin-Lecreulx D, Trent MS (2008b) Periplasmic phosphorylation of lipid A is linked to the synthesis of undecaprenyl phosphate. Mol Microbiol 67:264–277CrossRefGoogle Scholar
  85. Trunkfield AE, Gurcha SS, Besra GS, Bugg TD (2010) Inhibition of Escherichia coli glycosyltransferase MurG and Mycobacterium tuberculosis Gal transferase by uridine-linked transition state mimics. Bioorg Med Chem 18:2651–2663PubMedPubMedCentralCrossRefGoogle Scholar
  86. Ünligil UM, Rini JM (2000) Glycosyltransferase structure and mechanism. Curr Opin Struct Biol 10:510–517PubMedCrossRefGoogle Scholar
  87. Vollmer W, Blanot D, de Pedro MA (2008) Peptidoglycan structure and architecture. FEMS Microbiol Rev 32:149–167PubMedCrossRefGoogle Scholar
  88. Willey JM, van der Donk WA (2007) Lantibiotics: peptides of diverse structure and function. Annu Rev Microbiol 61:477–501PubMedCrossRefGoogle Scholar
  89. Zheng Y, Struck DK, Young R (2009) Purification and functional characterization of ΦX174 lysis protein E. Biochemistry 48:4999–5006PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Hélène Barreteau
    • 1
  • Didier Blanot
    • 1
  • Dominique Mengin-Lecreulx
    • 1
  • Thierry Touzé
    • 1
    Email author
  1. 1.Group Bacterial Cell Envelopes and Antibiotics, Institute for Integrative Biology of the Cell (I2BC)CEA, CNRS, Univ Paris Sud, Université Paris-SaclayGif-sur-YvetteFrance

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