Daniel E. Kahne
Board Member: 2003 - 2006
For many years our research group has been interested in the molecular mechanisms of various antibiotics and the fundamental cellular processes they inhibit. We have primarily focused on drugs that target bacterial cell wall biosynthesis, including the beta-lactams, vancomycin, and moenomycin. We use these molecules to study the protein machines that synthesize and degrade the bacterial cell wall. Mechanistic studies of these classes of enzymes provide insight into the factors that determine bacterial cell shape, growth, and division. Recently, we have also become interested in understanding how the structure of cellular membranes is established and maintained. This is a stereochemical problem since biological membranes are asymmetric and require proper spatial organization of their constituent lipids and proteins in order to function correctly. We use E. coli as our model system and have identified two protein complexes that are involved in assembling lipids and proteins in the outer membrane of Gram-negative bacteria. Our challenge now is to determine how these machines function at a detailed chemical level and to explore their potential as antibacterial targets. A combination of sophisticated organic synthesis, bacterial genetics, biochemistry, and structural biology are required in these efforts.