Kirsten Wolthers
B.Sc. (1996) University of
British Columbia
Ph.D. (2001) Oregon State University
Dr. Kirsten R. Wolthers

Room 342, Fipke Centre for Innovative Research
Departments of Chemistry, Earth & Environmental Sciences

University of British Columbia Okanagan
3333 University Way
Kelowna, British Columbia
CANADA V1V 1V7
Tel : 250 807 8663
Fax: 250 807 8005
Email: kirsten.wolthers@ubc.ca
Research Interests
Enzyme Catalysis on a Dynamic Landscape
Enzymes are dynamic entities - undergoing multi-scale conformational motion that ranges from small bond vibrations, to the movement of active site residues and flexible loops and occasionally large-scale domain motion. The coupling of protein dynamics to catalysis requires precise timing and control, and this is particularly true for enzymes that house highly oxidative free-radical intermediates or highly potent nucleophilic centres. Aberrant side reactions with O2 or with numerous radical scavengers that line the active site can and does lead to enzyme activation.
The research goal of the lab is to understand how enzymes synchronize this "risky" chemistry with multi-scale and multi-frequency dynamic motion. Our model enzyme systems contain cofactors (coenzyme B12, flavins and PLP) whose spectral properties change over the course of the catalytic cycle. As such, we use fast time resolved spectroscopic techniques to characterize their kinetic behavior. These kinetic studies are complemented by structural (X-ray crystallography), pulsed-EPR and computational analysis, giving us a clearer mechanistic picture for catalysis.
Engineering Radical-based Biocatalysts
Radicals are highly reactive molecules that can activate chemically inert substrates and initiate reactions with a high thermodynamic barrier. For this reason they are revered by chemists. But radicals are indiscriminant with a propensity for uncontrolled side reactions, and for this reason they are also considered a curse.
Several enzymes have evolved elegant means be which to harness the energy associated with radicals - directing them towards productive chemistry - eliminating unwanted and uncontrolled side reactions. As a result, these enzymes are able to perform reactions (cleavage of C-C, C-N and C-H bonds on chemically inert substrates) associated with a high energy of activation.
A research goal of the lab is to reengineer these radical-based enzymes to serve as biocatalysts. That is, (predictably) redesign the enzyme to perform the type of chemistry that is applicable to industry and the drug manufacturing. While this is an inherently challenging goal, the engineering of a radical-based enzyme will constitute a step-change in our understanding of enzyme-mediated radical-chemistry, and open new doors in the area of drug design.
Last reviewed 
3/30/2010 12:35:27 PM
