The primary goal of our research program is directed toward an understanding of cell wall biosynthesis on the molecular level. The synthesis, assembly, and amplification of this structure is catalyzed by an integrated series of membrane-associated enzymes that are carefully regulated by the organism. Our research will contribute to an understanding of these enzymes, membrane events in peptidoglycan synthesis, membrane-wall interrelationships, and membrane teichoic acid biosynthesis. In addition, it our goal to apply the results of our studies to the design of antibacterial agents that inhibit the assembly of cross-linked peptidoglycan. Five specific objectives will be undertaken. (1) Membrane events in cell wall biosynthesis including dynamics of the translocation process, heterogeneity of lipid intermediate population, and microenvironments experienced by these intermediates. (2) Membrane-wall interrelationships with emphasis on the factors that govern the lability of the system, on penicillin as a tool in studying the relationship, and on the topography of the DD-carboxypeptidase and lipid intermediate. (3) Purification and mechanistic analysis of phospho-MurNAc-pentapeptide translocase including lipid-translocase interactions. (4) Biosynthesis of membrane teichoic acid: incorporation of D-alanine. (5) Design of analogues of D-alanyl-D-alanine that are potential antibacterial agents. An investigation of these five projects will contribute to our understanding of cell wall assembly and membrane chemistry that relates to this process. Our present objectives will provide insights into the events, regulations, and translocations that occur in the bacterial membrane for elaboration of this extracellular structure, the cell wall.
NIH ExPorter
NIH ExPorter