Professor (Department of Biochemistry, Molecular Biology, and Biophysics)
- Chemical Biology, Metallo Enzymes
- Inorganic Chemistry
- Physical Chemistry, Biophysical Studies of Metalloenzymes
Principal Research Interests
We investigate the mechanisms of oxygenases, the enzymes nature uses to catalyze the incorporation of oxygen into biological molecules. Oxygen incorporation reactions are important for a wide variety of reasons, ranging from activation of steroid hormones in humans to the detoxification of compounds in the environment. The oxygenases we study contain a metal which is the key to the chemistry they catalyze. Enzyme mechanisms involve both the chemical reactions occurring at the active site and the regulation of the reaction imposed by the complex protein structure. Consequently, we use many types of biochemical and physical techniques including transient kinetics, site directed mutagenesis, diagnostic substrate reactions, and EPR spectroscopy. This is extended to X-ray crystallography and other spectroscopies through collaborations.
Currently, we are studying two large families of oxygenases. The first is typified by methane monooxygenases, the enzyme primarily responsible for preventing the vast amounts of biologically generated methane from reaching the atmosphere. This enzyme splits O2 and incorporates one atom of oxygen into methane to form methanol, while reducing the second atom to water. Another enzyme we have found from this family is essential for the biosynthesis of many important antibiotics and chemotherapy drugs. The second oxygenase family includes several dioxygenase enzymes that also split O2 but incorporate both atoms into biomolecules. These enzymes are the major means by which the enormous quantities of aromatic compounds that enter the environment annually are reassimilated into the carbon cycle. Recently, we have developed methods to trap reaction cycle intermediates of these enzymes in single crystals for direct structural analysis. Related collaborative projects include studies of the biosynthesis of biofuels, penicillin, fosfomycin, and ethylene (a plant hormone).
- John Lipscomb, University of Minnesota, Department of Chemistry
- Biochemistry, Molecular Biology, and Biophysics (delivery code 1214), 139 Smith Hall, 207 Pleasant St SE
- Minneapolis, MN 55455-0431