HAGER, Lowell P.

Department of Biochemistry
Ph.D. (1953) University of Illinois

   Research Topics

• Development of Eukaryotic Expression Vectors for Synthesis and Secretion of Protein
• Enzymatic Activation Mechanisms
• Biological Halogenation Mechanisms

   Research Interests  

   Our work is directed toward protein structure-function relationships, with special emphasis on enzyme activation mechanisms. One project involves mechanistic studies on chloroperoxidase and related halogenating enzymes which catalyze iodination, bromination, chlorination, and hydroxylation reactions. We are especially interested in enzymes involved in the biosynthesis of volatile halohydrocarbons such as CH$$₂Br$$₂, CH$$₃Br$$₃, and CH$$₃Cl. We have discovered a new enzyme, methyl chloride transferase, which catalyzes the synthesis of methyl chloride from S-adenosyl methionine and chloride ion. Many halophytic plants are rich sources of the enzyme. We are currently examining the metabolic role of methyl chloride transferase in halophytic plant metabolism. Our working hypothesis is that the transferase serves to regulate internal chloride ion concentrations by producing a volatile chlorine product.

We have cloned the structural gene (including signal sequence) of chloroperoxidase, a secreted halogenating enzyme from the mold Caldariomyces fumago. In addition to catalyzing halogenation reaction chloroperoxidase catalyzes enantioselective Epoxidation, sulfazidation and hydroxylation reactions.  Current effort evolves the isolation of "directed evolution" mutants having improved epoxidation activity.  We believe that chloroperoxidase can be engineered to make it a viable industrial catalyst.

   Recent investigations on the mechanisms of the halogenation reaction catalyzed by chloroperoxidase has revealed that it is related to the P$$₄₅₀ cytochromes, horseradish peroxidase and catalase. Studies involving site-specific mutagenesis of the structural gene for chloroperoxidase are now underway, and we believe that what we learn will tie together a lot of the chemistry in the heme containing proteins.

   Key Words   Recombinant DNA, Introduction of DNA into Plant Cells, Introduction of DNA into Fungal Cells, Gene Expression Systems, Site-Directed Mutagenesis, Membrane Structure and Function, Protein Purification and Characterization, Protein Processing and Secretion, Biocatalytic Conversions, Active Sites and Receptors, Molecular Modeling, Structural Biology, NMR

  Current Research Funding    NIH, 

BTC Members