Eduardus (Evert) Duin
Associate Professor
Biochemistry


(334) 844-6072
Email: duinedu@auburn.edu

Research Group



Biochemistry: mechanistic enzymology, metalloenzymes, EPR/ESR

Isoprene Synthesis and 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/MEP pathway. In humans and animals isoprenoids are derived from the mevalonate pathway. The DOXP/MEP pathway is the sole pathway in Eubacteria and apicomplexan parasites. Important multi-drug resistant and other pathogens belong to this group, causing for example malaria, tuberculosis, plague, cholera and anthrax. The goal of the proposed research is to fully characterize the proteins involved in the DOXP/MEP pathway and develop inhibitors specific for these proteins as potential anti-infective agents. We recently discovered the final two proteins in the DOXP/MEP pathway, GcpE/IspG and LytB/IspH, both of which contain a highly oxygen-sensitive [4Fe-4S] cluster in their active sites. The goal is to obtain a complete understanding of the reaction mechanism which will enable the development of inhibitors as possible drug candidates.

Methyl Coenzyme M Reductase

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.





Isoprene Synthesis:

  • Xu, W., Lees, N.S., Adedeji, D., Wiesner, J., Jomaa, H., Hoffman, B.M., Duin, E.C. (2010) Paramagnetic Intermediates of (E)-4-Hydroxy-3-methylbut-2-enyl Diphosphate Synthase (GcpE/IspG) under Steady-State and Pre-Steady-State Conditions. J. Am. Chem. Soc., 132, 14509-14520
  • Oldfield, E., Rekittke, I., Wiesner, J., Röhrich, R., Demmer, U., Warkentin, E., Xu, W., Troschke, K., Hintz, M., No, J.H., Duin, E., Jomaa, H., Ermler, U. (2008) Structure of (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase, the terminal enzyme of the non-mevalonate pathway. J. Am. Chem. Soc., 130, 17206 - 17207
  • Adedeji, D., Hernandez, H., Wiesner, J., Köhler, U., Jomaa, H., Duin, E.C. (2007) Possible direct involvement of the active-site [4Fe-4S] cluster of the GcpE enzyme from Thermus thermophilus in the conversion of MEcPP. FEBS Lett., 581, 279-283
  • Altincicek, B., Duin, E.C., Reichenberg, A., Hedderich, R., Kollas, A.-K., Hintz, M., Wagner, S., Wiesner, J., Beck, E., Jomaa, H. (2002) LytB protein catalyzes the terminal step of the 2-C-methyl-D-erythritol-4-phosphate pathway of isoprenoid biosynthesis. FEBS Lett., 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. (2002) Functional characterization of GcpE, an essential enzyme of the non-mevalonate pathway of isoprenoid biosynthesis. FEBS Lett., 532, 432-436

Methyl Coenzyme M Reductase:

  • Harmer, J., Finazzo, C., Piskorski, R., Ebner, S., Duin, E.C., Goenrich, M, Thauer, R.K., Reiher, M., Schweiger, A., Hinderberger, D., Jaun, B. (2008) A Nickel Hydride Complex in the Active Site of Methyl-Coenzyme M Reductase: Implications for the Catalytic Cycle, J. Am. Chem. Soc., 130, 10907-10920
  • Duin, E.C., McKee, M.L. (2008) A New Mechanism for Methane Production from Methyl-Coenzyme M Reductase As Derived from Density Functional Calculations. J. Phys. Chem. B, 112, 2466-2482
  • Yang, N., Reiher, M., Wang, M., Harmer, J., Duin, E.C. (2007) Formation of a nickel-methyl species in methyl-coenzyme M reductase, an enzyme catalyzing methane formation. J. Am. Chem. Soc., 129, 11028-11029



Last updated: 08/02/2011