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Comparative flux control through the cytoplasmic phase of cell wall biosynthesis

By Daniel James Bearup


The introduction of antibacterial drugs in the middle of the last century heralded a new era in\ud the treatment of infectious disease. However the parallel emergence of antibiotic resistance and\ud decline in new drug discovery threatens these advances. The development of new antibacterials\ud must therefore be a high priority.\ud The biosynthesis of the bacterial cell wall is the target for several clinically important antibacterials.\ud This extracellular structure is essential for bacterial viability due to its role in the\ud prevention of cell lysis under osmotic pressure. Its principal structural component, peptidoglycan,\ud is a polymer of alternating N-acetyl-glucosamine (GlcNAc) and N-acetyl muramic acid\ud (MurNAc) residues crosslinked by peptide bridges anchored by pentapeptide stems attached\ud to the MurNAc moieties. The biosynthesis of peptidoglycan proceeds in three phases. The\ud first, cytoplasmic, phase is catalysed by six enzymes. It forms a uridine diphosphate (UDP)\ud bound MurNAc residue from UDP-GlcNAc and attaches the pentapeptide stem. This phase is\ud a relatively unexploited target for antibacterials, being targeted by a single clinically relevant\ud antibacterial, and is the subject of this thesis.\ud The Streptococcus pneumoniae enzymes were kinetically characterised and in silico models of\ud this pathway were developed for this species and Escherichia coli. These models were used to\ud identify potential drug targets within each species. In addition the potentially clinically relevant\ud interaction between an inhibitor of and feedback loops within this pathway was investigated.\ud The use of direct parameter estimation instead of more traditional approaches to kinetic characterisation\ud of enzymes was found to have significant advantages where it could be successfully\ud applied. This approach required the theoretical analysis of the models used to determine\ud whether unique parameter vectors could be determined. Such an analysis has been completed\ud for a broad range of biologically relevant enzymes. In addition a relatively new approach to\ud such analysis has been developed

Topics: QP
OAI identifier: oai:wrap.warwick.ac.uk:4487

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  1. (1997). A A Medeiros. Evolution and dissemination of beta-lactamases accelerated by generations of beta-lactam antibiotics. doi
  2. (1992). A continuous spectrophotometric assay for inorganic phosphate and for measuring phosphate release kinetics in biological systems. doi
  3. (2003). A MurG assay which utilises a synthetic analogue of lipid I. doi
  4. (2003). A New View of the Mechanisms of UDP-N-Acetylglucosamine Enolpyruvyl Transferase(MurA) and 5-Enolpyruvylshikimate-3-phosphate Synthase(AroA) Derived from X-ray Structures of Their Tetrahedral Reaction Intermediate States. doi
  5. (2003). A Switch for the Transfer of Substrate between Nonribosomal Peptide and Polyketide Modules of the Rifamycin Synthetase Assembly Line. doi
  6. (1992). Active efflux mechanisms for antimicrobial resistance. doi
  7. (1999). AlterationBibliography 255 of a single amino acid residue reverses fosfomycin resistance of recombinant MurA from Mycobacterium tuberculosis.
  8. (1963). An Algorithm for Least-Squares Estimation of Nonlinear Parameters. doi
  9. (2008). An efficient tool to test global identifiability. Some case studies. Control and Automation, doi
  10. (1989). Analysis of progress curves by simulations generated by numerical integration.
  11. (2002). and A Rubio. 4-Substituted D-Glutamic Acid Analogues: The First Potent Inhibitors of Glutamate Racemase(MurI) Enzye with Antibacterial Activity. doi
  12. and A Tomasz. Perturbation of cell wall synthesis suppresses autolysis in Staphylococcus aureus: evidence for coregulation of cell wall synthetic and hydrolytic enzymes. doi
  13. (2006). Antibacterial Natural Products in Medicinal Chemistry-Exodus or Revival? Angew Chem Int Ed Engl, doi
  14. (1973). Approaches to the study of enzyme mechanisms lactate dehydrogenase. doi
  15. (1983). Automatic Selection of Methods for SOlving Stiff and Nonstiff Systems of Ordinary Differential Equations. doi
  16. (2008). Bacteria subsisting on antibiotics. doi
  17. (2007). Bacterial efflux pump inhibitors from natural sources. doi
  18. (2008). Bacterial peptidoglycan (murein) hydrolases. doi
  19. (1996). Bacterial resistance to vancomycin: five genes and one missing hydrogen bond tell the story. doi
  20. (2008). Bioinformatics identification of MurJ (MviN) as the peptidoglycan lipid II flippase in Escherichia coli. doi
  21. (1989). Bug/drug resistance. Sometimes less is more. doi
  22. (2006). Cell signalling dynamics in time and space. Nature reviews. Molecular cell biology, doi
  23. (2002). Cellular impermeability and uptake of biocides and antibiotics in Gram-negative bacteria. doi
  24. (2002). Cellular impermeability and uptake of biocides and antibiotics in Grampositive bacteria and mycobacteria. doi
  25. (1997). Characterisation of NADP+ binding to perdeuterated MurB: backbone atom NMR assignments and chemical shift changes. doi
  26. (2000). Characterization of a beta -N-acetylglucosaminidase of Escherichia coli and elucidation of its role in muropeptide recycling and beta -lactamase induction. doi
  27. (1996). Characterization of a Cys115 to Asp substitution in the Escherichia coli cell wall biosynthetic enzyme UDP-GlcNAc enolpyruvyl transferase (MurA) that confers resistance to inactivation by the antibiotic fosfomycin. doi
  28. (2008). Characterization of nucleotide pools as a function of physiological state in Escherichia coli. doi
  29. (1970). Cleavage of Structural proteins during the Assembly of the Head of Bacteriophage T4. doi
  30. (1992). Cloning and sequencing of Escherichia coli murZ and purification of its product, a UDP-N-acetylglucosamine enolpyruvyl transferase.
  31. (2000). Cloning, overexpression and purification of Pseudomonas aeruginosa murC encoding uridine diphosphate N-acetylmuramate: L-alanine ligase. doi
  32. (1969). Coenzyme content of purified alanine racemase from Pseudomonas. doi
  33. (2000). Comparative X-ray analysis of the un-liganded fosfomycin-target MurA. doi
  34. (2009). Computing representations for radicals of finitely generated differential ideals. Applicable Algebra in Engineering, doi
  35. Contribution of a thickened cell wall and its glutamine nonamidated component to the vancomycin resistance expressed by Staphylococcus aureus Mu50. Antimicrob Agents Chemother, doi
  36. (2006). COPASI - a COmplex PAthway SImulator. doi
  37. (2008). Cytoplasmic steps of peptidoglycan biosynthesis. doi
  38. Cytoplasmic steps of peptidoglycan synthesis in Escherichia coli. doi
  39. (1993). Description and Use of LSODE, the Livermore Solver for Ordinary Differential Equations. Reference Publication 1327, doi
  40. Detection and characterization of a phospholactoyl-enzyme adduct in the reaction catalyzed by UDP-Nacetylglucosamine enolpyruvoyl transferase, doi
  41. (1994). Detection of the covalent intermediate of UDP-N-acetyl glucosamine enolpyruvyl transferase by solution-state and time resolved solid-state NMR spectroscopy. doi
  42. (1989). Determination of murein precursors during the cell cycle of Escherichia coli. doi
  43. (2001). Differential algebra methods for the study of the structural identifiability of rational function state-space models in the biosciences. doi
  44. (1950). Differential Algebra. AMS Colloquium Publications, 1st edition,
  45. (1990). Differential plasmid rescue from transgenic mouse DNAs into Escherichia coli methylation-restriction mutants. doi
  46. (1994). Direct, real-time measurement of rapid inorganic phosphate release using a novel fluorescent probe and its application to actomyosin subfragment 1 ATPase. doi
  47. (2004). Diseases Society of America). Bad bugs, no drugs. As antibiotic discovery stagnates ...a public health crisis brews.,
  48. DNA topoisomerases: structure, function, and mechanism. doi
  49. (2004). Docking studies and model development of tea polyphenol proteasome inhibitors: Applications to Rational Drug Design. Proteins: Structure, Function and Bioinformatics, doi
  50. (2006). Does the cell wall of bacteria remain a viable source of targets for novel antibiotics? Biochemical pharmacology, doi
  51. (2009). EcoCyc: a comprehensive view of Escherichia coli biology. Nucleic Acids Research, 37(Database issue):D464–70, doi
  52. (1985). Effect of growth conditions on peptidoglycan content and cytoplasmic steps of its biosynthesis in Escherichia coli.
  53. (1997). Emergent antibiotic resistance: health risks and economic impact. doi
  54. (1971). Enzyme reactions in polymer media. doi
  55. (1992). Epidemiology of drug resistance: implications for a post-antimicrobial era. doi
  56. (1973). Equilibrium binding of nicotinamide nucleotides to lactate dehydrogenase.
  57. (1997). Etude alg´ ebrique et algorithmique des singularit´ es des ´ equations diff´ entielles implicites.
  58. (1992). Evidence for in vivo incorporation of D-lactate into peptidoglycan precursors of vancomycin-resistant enterococci. doi
  59. (2001). Evidence of a functional requirement for a carbamoylated lysine residue in MurD, MurE and MurF synthetases as established by chemical rescue experiments. doi
  60. (1993). Evidence that the reaction of the UDP-N-acetylglucosamine 1-carboxyvinyltransferase proceeds through the O-phosphothioketal of pyruvic acid bound to Cys115 of the enzyme. doi
  61. (1987). Evolution of an inducible penicillin-target protein in methicillin-resistant Staphylococcus aureus by gene fusion. doi
  62. (1997). Evolution of antibiotic resistance.
  63. (2004). Expression, purification and preliminary X-ray analysis of crystals of Bacillus subtilis glutamate racemase. Acta Crystallogr D Biol Crystallogr, 60(Pt 11):2031–4, doi
  64. (1995). Facsimile (Version 4.0) User Guide. doi
  65. (2008). Folding and membrane insertion of the pore-forming peptide gramicidin occur as a concerted process. doi
  66. (1999). Formation of adenosine 5’-tetraphosphate from the acyl phosphate intermediate: a difference between the MurC and MurD synthetases of Escherichia coli. doi
  67. (1988). Fractal Reaction Kinetics. doi
  68. (2006). Function and Dynamics in the mur Family of Bacterial Cell Wall Ligases. doi
  69. (1972). General mass action kinetics. Archive for Rational Mechanics and Analysis, doi
  70. (2002). Glucosamine-6-phosphate synthase–the multi-facets enzyme. doi
  71. (1986). Glycopeptide antibiotics: a mechanism-based screen employing a bacterial cell wall receptor mimetic. doi
  72. (1998). Growth of the stress-bearing and shape-maintaining murein sacculus of Escherichia coli.
  73. (1999). Health and economic outcomes of antibiotic resistance in Pseudomonas aeruginosa. doi
  74. (1982). Identifiability of deterministic differential models in state space.
  75. Identifiability of uncontrolled nonlinear rational systems. doi
  76. (2001). Identification and characterization of UDP-N-acetylenolpyruvylglucosamine reductase (MurB) from the Gram-positive pathogen Streptococcus pneumoniae. Biochem J, 355(Pt 2):431–5, doi
  77. (2008). Identification of an Inhibitor of the MurC Enzyme, Which Catalyzes and Essential Step in the Peptidoglycan Precursor Synthesis Pathway. Assay Drug Dev, doi
  78. (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.
  79. (1991). Identification of vancomycin resistance protein VanA as a D-alanine:D-alanine ligase of altered substrate specificity. doi
  80. (2009). Inactivation of the glycoside hydrolase NagZ attenuates antipseudomonal beta-lactam resistance in Pseudomonas aeruginosa. doi
  81. (2005). Inhibitors of efflux pumps in Gram-negative bacteria. doi
  82. (1992). Intracellular steps of bacterial cell wall peptidoglycan biosynthesis: enzymology, antibiotics, and antibiotic resistance. Natural product reports, 9(3):199–215, doi
  83. (1997). Invariant amino acids in the Mur peptide synthetases of bacterial peptidoglycan synthesis and their modification by site-directed mutagenesis in the UDP-MurNAc:L-alanine ligase from Escherichia coli. doi
  84. (2008). Involvement of an essential gene, mviN, in murein synthesis in Escherichia coli. doi
  85. (1993). Isolation and structural elucidation of a tetrahedral intermediate in the UDP-N-acetylglucosamine enolpyruvoyl transferase enzymic pathway. doi
  86. (1996). Kinetic and crystallographic studies of Escherichia coli UDP-N-acetylmuramate: L-alanine ligase. Protein Sci, doi
  87. (1997). Kinetic characterization of wild-type and S229A mutant MurB: evidence for the role of Ser 229 as a general acid. doi
  88. (1996). Kinetic mechanism of the Escherichia coli UDPMurNAc-tripeptide D-alanyl-D-alanine-adding enzyme: use of a glutathione S-transferase fusion. doi
  89. (1994). Kinetics, stoichiometry, and identification of the reactive thiolate in the inactivation of UDP-GlcNAc enolpyruvoyl transferase by the antibiotic fosfomycin. doi
  90. (2000). Large-scale prediction of phenotype: concept. doi
  91. (1974). Macroscopic rate constants involved in the formation and interconversion of the two central enzyme-substrate complexes of the lactate dyhrogenase turnover.
  92. (2000). Mathematical modelling of metabolism. doi
  93. Mechanism of bacitracin action: a specific lipid-peptide interaction. doi
  94. (1972). Mechanism of D-cycloserine action: alanine racemase from Escherichia coli W.
  95. (2009). MeropenemClavulanate Is Effective Against Extensively Drug-Resistant Mycobacterium tuberculosis. doi
  96. (1992). Meta-evolutionary programming. doi
  97. (1984). Metabolic resistance to tight-binding inhibitorsBibliography 252 of enzymes involved in the de novo pyrimidine pathway. Simulation of time-dependent effects. doi
  98. (1983). Metabolic resistance: the protection of enzymes against drugs which are tight-binding inhibitors by the accumulation of substrate. doi
  99. (1980). Microbial cell walls and membranes, chapter Structure of peptidoglycan, doi
  100. (2009). Modulation of cell wall structure and antimicrobial susceptibility by a Staphylococcus aureus eukaryote-like serine/threonine kinase and phosphatase. doi
  101. Molecular basis for vancomycin resistance in Enterococcus faecium BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA. doi
  102. (1993). Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes.
  103. (2000). Molecular mechanisms that confer antibacterial drug resistance.
  104. (2008). Multidrug-resistant tuberculosis. doi
  105. (2008). Murein (peptidoglycan) structure, architecture and biosynthesis in Escherichia coli. doi
  106. (2009). Mutational analysis of the substrate specificity of Escherichia coli penicillin binding protein 4. doi
  107. (1999). Negative regulation of the Pseudomonas aeruginosa outer membrane porin OprD selective for imipenem and basic amino acids.
  108. (2006). New antibiotics from bacterial natural products. doi
  109. (2007). Nitroimidazole action in Entamoeba histolytica: a central role for thioredoxin reductase. doi
  110. (1993). Nitroimidazole drugs–action and resistance mechanisms. I. Mechanisms of action. doi
  111. Non-linear effects of macromolecular crowding on enzymatic activity of multi-copper doi
  112. On calculation of rate and dissociation constants from kinetic constants for the ordered bi bi mechanism of liver alcohol dehydrogenase. doi
  113. (1994). On global identifiability for arbitrary model parametrizations. doi
  114. (1970). On Structural Identifiability. doi
  115. (2000). Open” structures of MurD: domain movements and structural similarities with folylpolyglutamate synthetase. doi
  116. (1991). Over-production, purification and properties of the uridine diphosphate N-acetylmuramoyl-L-alanine:D-glutamateligase from Escherichia coli. doi
  117. (1990). Over-production, purification and properties of the uridine-diphosphate-N-acetylmuramoyl-L-alanyl-Dglutamate: meso-2,6-diaminopimelate ligase from Escherichia coli. doi
  118. (1993). Overexpression, purification, and mechanistic study of UDP-N-acetylenolpyruvylglucosamine reductase. doi
  119. (2001). Pag` es. A new mechanism of antibiotic resistance in Enterobacteriaceae induced by a structural modification of the major porin. doi
  120. (1998). Pathway of ATP hydrolysis by monomeric and dimeric kinesin. doi
  121. (1983). Penicillin-Binding Proteins and the Mechanism of Action of Beta-Lactam Antibiotics1. Annu Rev Biochem, doi
  122. (2008). Peptide inhibitors of MurD and MurE, essential enzymes of bacterial cell wall biosynthesis. doi
  123. (2008). Peptidoglycan structure and architecture. doi
  124. (1972). Peptidoglycan types of bacterial cell walls and their taxonomic implications.
  125. (2008). Phage display-derived inhibitor of the essential cell wall biosynthesis enzyme MurF. doi
  126. (1996). Phosphinate Inhibitors of the DGlutamic Acid-Adding Enzyme of Peptidoglycan Biosynthesis. doi
  127. (1969). Porcine heart lactate dehydrogenase: optical rotatory dispersion, thermodynamics, and kinetics of binding reactions.
  128. (1997). Pre-steady-state kinetic analysis of 2-hydroxy-6-ketonona-2,4-diene-1,9-dioic acid 5,6-hydrolase: kinetic evidence for enol/keto tautomerization. doi
  129. (1998). Predicting temporal fluctuations in an intracellular signalling pathway. doi
  130. (1998). Prospects for Antiparasitic Drugs: The case of trypanosoma brucei, the causative agent of African Sleeping Sickness . doi
  131. (2005). Protein Production by auto-induction in high density shaking cultures. doi
  132. (1996). Proton-dependent multidrug efflux systems.
  133. (2004). Purification and characterization of the bacterial MraY translocase catalyzing the first membrane step of peptidoglycan biosynthesis. doi
  134. (1995). Purification and Properties of the Uridine-diphosphate-N-Acetylmuramate: l-alanine ligase from Escherichia coli. doi
  135. (2004). Reaction kinetics in intracellular environments with macromolecular crowding: simulations and rate laws. Progress in biophysics and molecular biology, 85(2-3):235–60, doi
  136. (1985). Release of cell wall peptides into culture medium by exponentially growing Escherichia coli.
  137. (1995). Representation for the radical of a finitely generated differential ideal. doi
  138. (1998). Research and development of antibacterial agents. doi
  139. (2005). Resistance to antibiotics: are we in the post-antibiotic era? doi
  140. Role of the ortholog and paralog amino acid invariants in the active site of the UDP-MurNAc-L-alanine:D-glutamate ligase (MurD). doi
  141. (2006). Selection of peptide inhibitors against the Pseudomonas aeruginosa MurD cell wall enzyme. doi
  142. (1998). Site-directed mutagenesis and chemical modification of the two cysteine residues of theBibliography 256 UDP-N-acetylmuramoyl:L-alanine ligase of Escherichia coli. doi
  143. (2003). Staphylococcal resistance revisited: community-acquired methicillin resistant Staphyloccocus aureus - an emerging problem for the management of skin and soft tissue infections. Curr Opin Infect Dis, doi
  144. (1995). Steady-state kinetic mechanism of Escherichia coli UDP-N-acetylenolpyruvylglucosamine reductase. doi
  145. (2008). Stoichiometric modelling of cell metabolism. doi
  146. (1999). Structural identifiability of controlled state space systems: aquasiautomated methodology for generating identifiable reparameterisation of unidentifiable systems. Symbolic Computation for Control (Ref. doi
  147. (1984). Structural identifiability of linear, bilinear, polynomial and rational systems. doi
  148. (2008). Structural variation in the glycan strands of bacterial peptidoglycan. doi
  149. (2003). Structure and function of the Mur enzymes: development of novel inhibitors. doi
  150. Structure of an enzyme required for aminoglycoside antibiotic resistance reveals homology to eukaryotic protein kinases. doi
  151. (1967). Structure of the cell wall of Staphylococcus aureus, strain Copenhagen. VII. Mode of action of the bacteriolytic peptidase from Myxobacter and the isolation of intact cell wall polysaccharides. doi
  152. (1996). Structure of UDP-N-acetylglucosamine enolpyuvyl transferase, an enzyme essential for the synthesis of bacterial peptidoglycan, complexed with substrate UDP-N-acetylglucosamine and the drug fosfomycin. doi
  153. Studies on transformation of Escherichia coli with plasmids. doi
  154. (2008). Synthesis and biological evaluation of N-acylhydrazones as inhibitors of MurC and MurD ligases. doi
  155. (1978). System Identifiability Based on the Power Series Expansion of the Solution. doi
  156. (2006). Systems biology, metabolic modelling and metabolomics in drug discovery and development. Drug discovery today, doi
  157. The 1.9 A crystal structure of Escherichia coli MurG, a membrane-associated glycosyltransferase involved in peptidoglycan biosynthesis. doi
  158. (1951). The Accelerated and StoppedFlow Methods for the Measurement of the Reaction Kinetics and Spectra of Unstable Compounds in the Visible Region of the Spectrum. Review of Scientific Instruments, doi
  159. (2006). The application of systems biology to drug discovery. doi
  160. (2001). The ATPase reaction cycle of yeast DNA topoisomerase II. Slow rates of ATP resynthesis and P(i) release. doi
  161. (2006). The beta-lactamase threat in Enterobacteriaceae, Pseudomonas and Acinetobacter. Trends in doi
  162. (2008). The biosynthesis of peptidoglycan lipid-linked intermediates. doi
  163. (1999). The C-terminal half of RNase E, which organizes the Escherichia coli degradosome, participates in mRNA degradation but not rRNA processing in vivo. doi
  164. The chain length of the glycans in bacterial cell walls.
  165. (1998). The challenge of antibiotic resistance. doi
  166. (2004). The challenge of emerging and re-emerging infectious diseases. Nature, doi
  167. (1992). The crisis in antibiotic resistance. doi
  168. The global situation of MDR-TB. doi
  169. (1996). The Gram stain after more than a century. Biotechnic and histochemistry, doi
  170. (2003). The impact of antimicrobial resistance on health and economic outcomes. doi
  171. (1996). The kinetic characterization of Escherichia coli MurG using synthetic substrate analogues. doi
  172. (1973). The kinetics of the interconversion of intermediates of the reaction of pig muscle lactate dehydrogenase with oxidised nictoninamide-adenine dinucleotide and lactate.
  173. (2006). The mechanism distinguishability problem in biochemical kinetics: The single-enzyme, single-substrate reaction as a case study. doi
  174. (1974). The mechanism of action of fosfomycin (phosphonomycin). doi
  175. (1980). The mechanism of action of penicillin. Penicillin acylates the active site of Bacillus stearothermophilus D-alanine carboxypeptidase.
  176. (2006). The mechanism of action of ramoplanin and enduracidin. doi
  177. (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. doi
  178. (1993). The murI gene of Escherichia coli is an essential gene that encodes a glutamate racemase activity. doi
  179. (2008). The penicillin-binding proteins: structure and role in peptidoglycan biosynthesis. doi
  180. (1989). The problem of model indistinguishability in pharmacokinetics. doi
  181. (2006). The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis, 42 Suppl 2:S82–9, doi
  182. (2000). The structural basis of ribosome activity in peptide bond synthesis. doi
  183. (2005). The structural identifiability of the susceptible infected recovered model with seasonal forcing. doi
  184. (1996). The structure of the substrate-free form of MurB, an essential enzyme for the synthesis of bacterial cell walls. doi
  185. (2005). The substrate specificity of peptidoglycan biosynthesis enzymes from Streptococcus pneumoniae.
  186. (1972). Topics in pharmacokinetics–IV: Approximation in Process Space and Fitting by Sums of Exponentials. doi
  187. (1999). Topological analysis of the MraY protein catalysing the first membrane step of peptidoglycan synthesis. doi
  188. (1973). Treatment of Enzyme Kinetic Data III. The use of the full time course of a reaction, as examined By computer simulation, in defining enzyme mechanisms.
  189. (2000). Two active forms of UDP-N-acetylglucosamine enolpyruvyl transferase in gram-positive bacteria. doi
  190. (1968). Two aspartokinases from Escherichia coli. Nature of the inhibition and molecular changes accompanying reversible inactivation. doi
  191. Uberdle isolirte Farbung der Schizomyceten in Schnltt-und Trockenpraparaten. Fortschr Med, doi
  192. (2005). UDP-N-acetylmuramic acid (UDP-MurNAc) is a potent inhibitor of MurA (enolpyruvyl-UDP-GlcNAc synthase). doi
  193. (2002). Why are bacteria refractory to antimicrobials?
  194. (1995). Why does Escherichia coli recycle its cell wall peptides? doi
  195. (1988). Why Does the Wronskian Work. doi
  196. (2003). Why is Big Pharma getting out of antibacterial drug discovery? doi

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