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Dale Poulter

John A. Widtsoe and Distinguished Professor of Chemistry and Professor of Biochemistry

B.S. Louisiana State University

Ph.D. University of California, Berkeley

Research

References

poulter@chemistry.utah.edu

Dale Poulter's Lab Page

Dale Poulter's PubMed Literature Search

Research

My research group is interested in problems at the interface between chemistry and biology. We are studying the prenyl transfer enzymes in the isoprenoid biosynthetic pathway to determine the mechanisms of the reactions they catalyze, how the proteins promote catalysis, and phylogenetic relationships among the enzymes.

The isoprenoid biosynthetic pathway is needed by all organisms to produce essential compounds. There are two different ways that nature synthesizes isopentenyl diphosphate (IPP) to dimethylallyl diphosphate (DMAPP),the fundamental five-carbon building blocks needed for isoprenoid biosynthesis. One of these pathways, the mevalonate (MVA) route, was discovered in the late 1950’s and until recently was assumed to be the only pathway to IPP and DMAPP. Recently, a second route, the methylerythrose phosphate (MEP) pathway, was discovered. We have cloned genes for several of the enzymes in the MEP pathway in order to study their mechanisms and to develop inhibitors that block the MEP pathway that have potential applications as new antibacterial agents.

We are also studying several key enzymes in the pathway that catalyze fundamental activation and bond forming reactions, including isomerization DMAPP, the addition of IPP to allylic isoprenoid diphosphates to make longer chains, and the cyclopropanation and rearrangement reactions that convert farnesyl diphosphate (FPP) to squalene during biosynthesis of cholesterol. Other enzymes we study are those catalyzing unusual alkylation reactions that occur during the biosynthesis ergot alkaloids, the posttranslational modification of proteins with isoprenoid chains, and the modification of tRNA. We isolate genes for the enzymes we study, engineer plasmids to overproduce the proteins, and carry out site-directed mutagenesis to help determine the roles of specific amino acids in binding and chemical catalysis. Work on these projects provides training in a combination of chemical (synthesis, isolation-identification, reaction mechanisms), microbiology (mutagenesis, isolation and characterization of genes), molecular biological (cloning, site-directed mutagenesis), and biochemical (enzyme purification, kinetics) techniques.

Much of what we do relies heavily on modern analytical methods, including high field multi-dimensional NMR, mass spectrometry, and separation technology. We also draw on ideas and techniques from chemistry and biology to design our experiments, including developing news procedures for the synthesis of compounds, developing new methods for measuring interactions between an enzyme and its substrates, and using recombinant DNA technology to engineer bacterial strains with new biosynthetic capabilities. It is the interdisciplinary nature of what we do that is both challenging and exciting.

References