Essential Iron

Complex biochemical systems depend on the interplay of many elements. Iron, an essential element for almost all living things, is also insoluble and therefore highly unavailable in aerobic, neutral environments. The microbes which serve as entry-points for iron into biogeochemical cycles, as well as the microbes which inhabit us, must overcome this challenge in order to survive. We are interested in the mechanisms that both pathogens and environmental microbes use to acquire iron from difficult sources.

Targeting pathogens. Inhibiting iron uptake by pathogens is one means of arresting their growth. Our work in this area focuses on describing the structures, mechanisms, and inhibitory properties of enzymes involved in iron uptake by pathogenic bacteria, including a set of enzymes from the widespread hospital pathogen Klebsiella pneumonia, and selected homologs from Aspergillus fumigatus and Mycobacterium tuberculosis.

Environmental applications. The activities of environmental microbes engaged iron cycling, on the other hand, are fundamental to life on earth. At the same time, the same microbes release other unwanted heavy metals into the biosphere, including toxic and radioactive species. Our work in this area focuses on the environmental Pseudomonad, P. mendocina ymp. We are developing molecular biological, genetic, and genomic tools for use with this organism, and applying them toward answering environmentally relevant questions.

Turning toxins into O₂

Biological and inorganic chemistry literally meet in the environment. We are interested in how microbes isolated from challenging environments carry out useful, unusual, and sometimes chemically difficult transformations as they make their living. In particular, many chemical strategies for catalysis and energy-generation have evolved in the absence of Nature's favorite oxidant, dioxygen. Recently, organisms have been isolated that are capable of using chlorooxides - highly toxic, man-made, and very environmentally pervasive oxidants used broadly as rocket propellants, herbicides, and bleaches. These include perchlorate, chlorate, and chlorite - as respiratory substrates. We are isolating and characterizing two enzymes involved in reductively detoxifying these substrates to harmless Cl- and O₂. These enzymes may inspire an elegant natural solution to a man-made problem.

Our day-to-day work involves a particularly rich variety of methods, including protein biochemistry, active site structure-mechanism analysis, comparative genomics, quantitative gene expression analysis, and spectroscopy. We also work closely with collaborators who work in chemistry, microbiology, geochemistry, and crystallography. All of our work supports efforts to improve human and environmental health.