Metal Ions in biology allow for an expanded chemical repertoire with the local protein environment and metal coordination sphere acting synergistically to impart unusual capabilities. It is therefore not surprising that the reactions catalyzed by metalloenzymes are chemically challenging and essential for life. This proposal focuses the complex metalloenzymes involved in anaerobic CO2 fixation. With greenhouse gases and climate change receiving renewed attention due to Superstorm Sandy and the recent droughts in the Midwest, we seek to understand the chemistry by which microbes convert the greenhouse gas CO2 into a metabolic carbon source. Our approach involves a variety of biophysical methods, which will allow us to visualize the hand-off of one-carbon units between enzymes in this pathway, as well as to probe the structural basis for enzymatic generation of low-potential electrons, which drive the chemistry of the pathway. By combining X-ray crystallography, small-angle X-ray scattering, analytical ultracentrifugation, isothermal titration calorimetry, and electron microscopy, we will explore the mechanism of action of the complex metalloenzymes in anaerobic CO2 fixation.

Public Health Relevance

Our structure/function studies of the enzymes of the Wood-Ljungdahl pathway of anaerobic carbon dioxide fixation provide insight into how microbes can convert a greenhouse gas into a metabolic carbon source. Our findings have applications in the synthesis of biomimetic catalysts for environmental remediation, in the engineering of biosynthetic pathways for the conversion of carbon dioxide into biofuels, and in the design of antiparasitic medicines. With climate change emerging as a major health concern, these studies are timely.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Macromolecular Structure and Function E Study Section (MSFE)
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Smith, Ward
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Massachusetts Institute of Technology
Schools of Arts and Sciences
United States
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Kung, Yan; Ando, Nozomi; Doukov, Tzanko I et al. (2012) Visualizing molecular juggling within a B12-dependent methyltransferase complex. Nature 484:265-9
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