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C. Dale Poulter BIOORGANIC CHEMISTRY John A. Widtsoe Distinguished Professor and Chair B.S., Louisiana State University, 1964 Ph.D., University of California, Berkeley, 1967 NIH Postdoctoral Fellow, University of California, Los Angeles, 1967 Phone: 801-581-6685 Office: 2274 HEB-N Email: poulter@chem.utah.edu Research Group Publications

Activities & Awards

• James Flack Norris Award, American Chemical Society
• Repligen Award, Biological Division, American Chemical Society
• Ernest Guenther Award, American Chemical Society
• Arthur C. Cope Scholar Award, American Chemical Society
• Alfred P. Sloan Fellow
• National Institute of Health Research Career Development Award
• Rosenblatt Prize, University of Utah
• David P. Gardner Fellow
• Distinguished Research Award, University of Utah
• Utah Award, American Chemical Society
• The Governor's Medal for Science and Technology
• Editor-in-Chief, Journal of Organic Chemistry
• Executive Committee, Biological Division of the American Chemical Society
• Fellow, American Academy of Arts and Sciences

Research Interests

My research group is interested in problems at the interface between organic chemistry and biochemistry. We study reactions catalyzed by enzymes in the isoprene biosynthetic pathway with special emphasis on establishing the mechanisms of the enzyme-catalyzed transformations and how the enzymes promote the reactions.

We also study structure-function relationships in peptides and proteins to determine how the particular topology of a complex biological molecule is related to its function as a catalyst or a ligand for receptor binding.

The isoprene biosynthetic pathway is needed by all organisms to produce essential compounds. We are studying several key enzymes in the pathway that catalyze fundamental reactions, including the isomerization of isopentenyl diphosphate (IPP) to dimethylallyl diphosphate (DMAPP), the condensation of IPP with a variety of allylic diphosphates to yield new allylic isoprenylogues containing five additional carbons, the unusual rearrangement of presqualence diphosphate (PSPP) to squalene during biosynthesis of cholesterol, and the posttranslational modifications of proteins by isoprenoid units that are important in cell signalling events. We are also studying unusual isoprenoid alkylations that occur during biosynthesis of ergot alkaloids, post-translational modifications of proteins, and in transfer RNAs.

We are isolating genes for the enzymes we study, construct plasmids for overexpression of the enzymes, and carrying out side-directed mutagenesis on critical amino acids to elucidate their role in catalysis. All of the reactions presented above are interesting biological alkylations in that they do not rely on commonly observed carbonyl group chemistry for construction of carbon-carbon and carbon--heteroatom bonds.Work in this area provides training in a combination of biochemical (purification of enzymes, kinetics, precursor-product studies) and chemical (synthesis, isolation-identification, reaction mechanisms) techniques.

Much of what we do relies heavily on modern analytical methods such as high pressure liquid chromatography, high field multinuclear magnetic resonance spectroscopy, and gas chromatography-mass spectrometry. We draw on ideas and techniques from organic chemistry and biochemistry to design our experiments, including developing new procedures for synthesis of compounds, developing new methods for measuring interactions between an enzyme and its substrates, and using recombinant DNA technology to obtain biological molecules that are normally difficult to isolate. It is the interdisciplinary nature of our work that we find both challenging and exciting.

Selected Publications

• Testa, C.A.; Lherbet, C.; Pojer, F.; Noel, J.P; Poulter, C.D. "Cloning and Expression of IspDF from Mesorhizobium loti.  Characterization of a Bifunctional Protein that Catalyzes Non- Consecutive Steps in the Methylerythritol Phosphate Pathway" Biochem. Biophys. Acta 2006, 1764, 85-96.
• Cornish, R.M.; Roth, J.R.; Poulter, C.D. "Lethal mutations in the isoprenoid pathway of Salmonella enterica" J. Bacteriol. 2006, 188, 1444-1450.
• Lherbet, C.; Pojer, F.; Richard, S.B.; Noel, J.P.; Poulter, C.D. "Absence of Substrate Channeling between Active Sites in the Agrobacterium tumefaciens IspDF and IspE Enzymes of the Methyl Erythritol Phosphate Pathway" Biochemistry 2006, 45, 3548-3553.
• Thulasiram, H.V.; Phan, R.M.; Rivera, S.B.; Poulter, C.D. "Synthesis of Deuterium Labeled Derivatives of Dimethylallyl Diphosphate" J. Org. Chem. 2006, 71, 1739-1741.
• Gauchet, C.; Labadie, G.R.; Poulter, C.D. "Regio- and Chemoselective Covalent Immobilization of Proteins through Unnatural Amino Acids" J. Am. Chem. Soc. 2006, 128, 9274-9275.
• Lee, S.; Poulter, C.D. "Escherichia coli Type I Isopentenyl Diphosphate Isomerase:  Structural and Catalytic Roles for Divalent Metals" J. Am. Chem. Soc. 2006, 128, 11545-11550.
• Lherbet, C.; Pojer, F.; Richard, S.B.; Noel, J.P.; Poulter, C.D. “Absence of Substrate Channeling between Active Sites in the Agrobacterium tumefaciens IspDF and IspE Enzymes of the Methyl Erythritol Phosphate Pathway” Biochemistry 2006, 45, 3548-3553.
• Gauchet, C.; Labadie, G.R.; Poulter, C.D. “Regio- and Chemoselective Covalent Immobilization of Proteins through Unnatural Amino Acids” J. Am. Chem. Soc. 2006, 128, 9274-9275.
• Lee, S.; Poulter, C.D. “Escherichia coli Type I Isopentenyl Diphosphate Isomerase:  Structural and Catalytic Roles for Divalent Metals” J. Am. Chem. Soc. 2006, 128, 11545-11550.
• Thulasiram, H.V.; Poulter, C.D. “Farnesyl Diphosphate Synthase: The Art of Compromise between Substrate Selectivity and Stereoselectivity” J. Am. Chem. Soc. 2006, 128, 15819-15823.
• Rothman, S.C.; Helm, T.R.; Poulter, C.D. “Kinetic and Spectroscopic Characterization of Type II Isopentenyl Diphosphate Isomerase from Thermus thermophilus:  Evidence for Formation of Substrate-induced Flavin Species” Biochemistry 2007, 46, 5437-5445.
• Thulasiram, H.V.; Erickson, H.K.; Poulter, C.D. “Chimeras of Two Isoprenoid Synthases Catalyze all Four Coupling Reactions in Isoprenoid Biosynthesis” Science 2007, 316, 73-76.
• Johnston, J.B.; Walker, J.R.; Rothman, S.C.; Poulter, C.D. “Type-2 Isopentenyl Diphosphate Isomerase.  Mechanistic Studies with Cyclopropyl and Epoxy Analogs” J. Am. Chem. Soc. 2007, 129, 7740-7741.