Publications

• A cell wall recycling shortcut that bypasses peptidoglycan de novo biosynthesis.

  Gisin J., Schneider A., Naegele B., Borisova M., Mayer C.

  We report a salvage pathway in Gram-negative bacteria that bypasses de novo biosynthesis of UDP N-acetylmuramic acid (UDP-MurNAc), the first committed peptidoglycan precursor, and thus provides a rationale for intrinsic fosfomycin resistance. The anomeric sugar kinase AmgK and the MurNAc α-1-phosp ... >> More

  We report a salvage pathway in Gram-negative bacteria that bypasses de novo biosynthesis of UDP N-acetylmuramic acid (UDP-MurNAc), the first committed peptidoglycan precursor, and thus provides a rationale for intrinsic fosfomycin resistance. The anomeric sugar kinase AmgK and the MurNAc α-1-phosphate uridylyl transferase MurU, defining this new cell wall sugar-recycling route in Pseudomonas putida, were characterized and engineered into Escherichia coli, channeling external MurNAc directly to peptidoglycan biosynthesis. << Less

  Nat. Chem. Biol. 9:491-493(2013) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Crystal structure of the N-acetylmuramic acid alpha-1-phosphate (MurNAc-alpha1-P) uridylyltransferase MurU, a minimal sugar nucleotidyltransferase and potential drug target enzyme in Gram-negative pathogens.

  Renner-Schneck M., Hinderberger I., Gisin J., Exner T., Mayer C., Stehle T.

  The N-acetylmuramic acid α-1-phosphate (MurNAc-α1-P) uridylyltransferase MurU catalyzes the synthesis of uridine diphosphate (UDP)-MurNAc, a crucial precursor of the bacterial peptidoglycan cell wall. MurU is part of a recently identified cell wall recycling pathway in Gram-negative bacteria that ... >> More

  The N-acetylmuramic acid α-1-phosphate (MurNAc-α1-P) uridylyltransferase MurU catalyzes the synthesis of uridine diphosphate (UDP)-MurNAc, a crucial precursor of the bacterial peptidoglycan cell wall. MurU is part of a recently identified cell wall recycling pathway in Gram-negative bacteria that bypasses the general de novo biosynthesis of UDP-MurNAc and contributes to high intrinsic resistance to the antibiotic fosfomycin, which targets UDP-MurNAc de novo biosynthesis. To provide insights into substrate binding and specificity, we solved crystal structures of MurU of Pseudomonas putida in native and ligand-bound states at high resolution. With the help of these structures, critical enzyme-substrate interactions were identified that enable tight binding of MurNAc-α1-P to the active site of MurU. The MurU structures define a "minimal domain" required for general nucleotidyltransferase activity. They furthermore provide a structural basis for the chemical design of inhibitors of MurU that could serve as novel drugs in combination therapy against multidrug-resistant Gram-negative pathogens. << Less

  J. Biol. Chem. 290:10804-10813(2015) [PubMed] [EuropePMC]