James G. Ferry Stanley Person Professor and Director, Center for Microbial Structural Biology 205 S. Frear Laboratory, University Park, PA 16802 Phone: (814) 863-5721 Fax: (814) 863-6217 E-mail: jgf3@psu.edu B.S. University of Georgia Ph.D. University of Illinois Ferry Lab Web Site

Enzymology and Functional Genomics

All life is classified into one of three "domains." Procaryotes in the Archaea domain evolved separately from bacteria (Bacteria domain) and are more closely related to eucaryotes (Eucarya domain). We study the enzymology and molecular genetics of anaerobic microbes from the Archaea domain to learn about the mechanism and molecular evolution of enzymes and other fundamental cellular processes common to all three domains. For example, two enzymes under investigation (acetate kinase and phosphotransacetylase) are key to obtaining energy for several pathogenic anaerobes. Studies on the mechanisms of these enzymes are designed to identify inhibitors with the potential to become new classes of antibiotics. Our studies have also led to the discovery of several new enzymes with structures and reaction mechanisms novel to all of biology. Our research on ancient enzymes from the Archaea is contributing to an understanding of the origin and evolution of life and directly impacts the emerging field of Astrobiology. The research approaches are divided into two areas. The first involves biochemical studies of enzyme mechanisms. For example, spectroscopic methods such as electron paramagnetic resonance are used to characterize redox-active metal centers. The second area of research concerns functional genomics. We have obtained the sequence of the entire genome of Methanosarcina thermophila (a methane-producing anaerobe from the Archaea domain) in collaboration with private industry. Our analysis of the genome is leading to the discovery of still more novel enzymes for which investigations into structure/function await. Microarray (DNA chip) technology is being used to investigate mechanisms of transcriptional regulation in the Archaea and the discovery of other fundamental cellular processes essential to all forms of life.

Anaerobes--microbes living without oxygen--comprise nearly one-fourth of all living protoplasm on earth and are found in a variety of habitats. They are found in animals and plants that are healthy or diseased, such as:

• human, animal, and plant infections
• the rumen of cattle
• the intestines of humans and other monogastric animals

Anaerobes in the environment convert biomass to methane in a process that is critical to the global carbon cycle. The anaerobic decomposition of biomass to methane and carbon dioxide occurs in vast and diverse anaerobic habitats such as:

• deep-sea hydrothermal vents
• marine and freshwater sediments
• rice paddies and other agricultural environments

The process of methanogenesis impacts the environment and human health in other important ways:

• biologically produced methane is a major component of greenhouse gases
• the process is used commercially to dispose of domestic and industrial wastes
• many anaerobes are able to detoxify hazardous pesticides, and
• methane from renewable biomass is a clean-burning alternative energy source.

Novel gamma class of carbonic anhydrase from the archaea.

Representative Publications:

• Tripp, B. C., C. B. Bell III, F. Cruz, C. Krebs, and J. G. Ferry. 2004. A role for iron in an ancient carbonicanhydrase. Journal of Biological Chemistry 279:6683-6687.
• Gorrell, A., S. H. Lawrence, and J. G. Ferry 2005. Structural and kinetic analyses of arginine residues in the active-site of the acetate kinase from Methanosarcina thermophila Journal of Biological Chemistry. 280:10731-10742.
• Moran, J. J., C. H. House, K. H. Freeman, and J. G. Ferry. 2005. Trace methane oxidation studied in several Euryarchaeota under diverse conditions. Archaea. 1:303-309.
• Andrade, S. L. A, F. Cruz, C. L. Drennan, V. Ramakrishnan, D. C. Rees, J. G. Ferry, and O. Einsle. 2005. Structures of the iron-sulfur flavoproteins from Methanosarcina thermophila and Archaeoglobus fulgidus. Journal of Bacteriology. 187:3848-3854.
• Li, Q., L. Li, T. Rejtar, B. L. Karger, and J. G. Ferry. 2005. The proteome of Methanosarcina acetivorans. Part I, an expanded view of the biology of the cell. Journal of Proteome Research. 4:112-128.
• Li, Q., L. Li, T. Rejtar, D. J. Lessner, B. L. Karger, and J. G. Ferry. 2006. Electron transport in the pathway of acetate conversion to methane in the marine archaeon Methanosarcina acetivorans. Journal of Bacteriology. 188:702-710.

Search the MEDLINE database at PubMed for articles by J.G.Ferry