Evert C. Duin

Assistant Professor

University of Amsterdam, Ph.D., 1996

University of Georgia, Postdoctoral, 1996-1998

Max Planck Institute for Terrestrial Microbiology, Humboldt fellow/MPI fellow, 1999-2002

email: duinedu@auburn.edu

web: www.auburn.edu/~duinedu/

Biochemistry: mechanistic enzymology, metalloenzymes, EPR/ESR

Biodefense

Isoprenoids are a group of essential biomolecules present in all organisms, some examples of which are cholesterol, steroid hormones, and ubiquinones. Recently it was discovered that two pathways exists that are used to synthesize isoprenoids, the mevalonate pathway and the DOXP pathway. In humans and animals isoprenoids are derived from the mevalonate pathway. The DOXP pathway is the sole pathway in Eubacteria. Important multi-drug resistant pathogens belong to this group, including Pseudomonas species, the main cause of infection in hospitals, and bacteria that cause tuberculosis, plague, cholera and anthrax. Plasmodium species that cause malaria also use this pathway. The goal of the proposed research is to fully characterize the proteins involved in the DOXP pathway and develop inhibitors specific for these proteins as potential anti-infective agents. We recently discovered the final two proteins in the DOXP pathway, GcpE and LytB, both of which contain a highly oxygen-sensitive [4Fe-4S] cluster in their active sites. The goal is to develop inhibitors of which the design is supported by data obtained on the 3D structures of the proteins as well as a complete understanding of their reaction mechanisms.

Methane

The production of the greenhouse gas methane by methanogenic archaea and the anaerobic activation of methane have long been considered to be separate processes. Recently, however, it was discovered that both processes are catalyzed by the same enzyme: methyl-coenzyme M reductase (MCR). The active site of MCR contains the nickel tetrahydrocorphinoid, cofactor 430 (F430). The long-term goals of our research are to understand the actual mechanism of methane production and the regulation of MCR activity by the cell. A successful outcome will provide important insight into how to slow down livestock methane production and production in rice fields. Both processes contribute to global warming due to the fact that methane is a potent greenhouse gas. Since MCR is also involved in methane activation, understanding the reaction mechanism will provide important information for the design of novel nickel-based catalysts that can perform this function. A process that is very important for the petrochemical industry.

 Selected Publications:

Duin, E.C. Role of coenzyme F430 in methanogenesis. In: Tetrapyrroles: their birth, life and death, (Eds. Warren, M.J., Smith, A.), Landes Bioscience, Georgetown, 2006, in press.

Harmer, J., Finazzo, C., Piskorski, R., Bauer, C., Jaun, B., Duin, E.C., Goenrich, M., Thauer, R.K., van Doorslaer, S., Schweiger, A. Spin density and coenzyme M coordination geometry of the ox1 form of methyl-coenzyme M reductase: A pulse EPR study. J. Am. Chem. Soc., 2005, 127, 17744-17755.

Duin, E.C., Signor, L., Piskorski, R., Mahlert, F., Clay, M.D., Goenrich, M., Thauer, R.K., Jaun, B., Johnson, M.K. Spectroscopic investigation of the nickel-containing porphinoid cofactor F430. Comparison of the free cofactor in the +1, +2 and +3 oxidation states with the cofactor bound to methyl coenzyme M reductase in the silent, red and ox forms. J. Biol. Inorg. Chem., 2004, 9, 563-576.

Altincicek, B., Duin, E.C., Reichenberg, A., Hedderich, R., Kollas, A.-K., Hintz, M., Wagner, S., Wiesner, J., Beck, E., Jomaa, H. LytB protein catalyzes the terminal step of the 2-C-methyl-D-erythritol-4-phosphate pathway of isoprenoid biosynthesis. FEBS Lett., 2002, 532, 437-440.

Kollas, A.-K, Duin, E.C., Eberl, M., Altincicek, B., Hintz, M., Reichenberg, A., Henschker, D., Henne, A., Steinbrecher, I., Ostrovsky, D.N., Hedderich, R., Beck, E., Jomaa, H., Wiesner, J. Functional characterization of GcpE, an essential enzyme of the non-mevalonate pathway of isoprenoid biosynthesis. FEBS Lett., 2002, 532, 432-436.