Document Type


Degree Name

Master of Science (MSc)




Faculty of Science

First Advisor

Dr. Geoff Horsman

Advisor Role

Associate Professor

Second Advisor

Dr. Joel Weadge

Third Advisor

Dr. Stephen MacNeil


Epoxide hydrolases (EHs) are enzymes that catalyze the ring opening of an epoxide, yielding a vicinal diol. This exciting class of enzymes is often associated with natural product and small molecule biosynthesis. One interesting class of natural products that epoxide hydrolases are involved in the biosynthesis of is the enediynes. Previously, 5 enediyne-associated epoxide hydrolases have been characterized, revealing an inverting-versus-retaining paradigm for enediyne epoxide hydrolases. The work described herein sets the table for future studies involving the probing of the α/β-epoxide hydrolase mechanism for styrene oxide. Kinetic and regioselectivity characterization of the enediyne-associated CynF and SghF has determined that SghF may be a robust starting platform for engineering efforts in the hopes of generating enantiomerically pure diols through biocatalysis. SghF represents the most efficient (Kcat/Km of 190 for (S)-styrene oxide) and enantioselective (E=655, in favour of the (S)-epoxide) enediyne-associated epoxide hydrolase characterized to date. The identification of conserved residues at positions Y138, L187, A188, D189, P190, E191, H192, A194, F229, Q303, L304, and Q370 may represent critical sites for investigation in the hopes of generating a robust catalytic toolkit for the production of enantiomerically pure diols from a wide variety of epoxide hydrolases and substrates. Finally, regioselectivity characterization of CynF and SghF has confirmed that CynF is a retaining epoxide hydrolase, and SghF is an inverting epoxide hydrolase, thereby expanding the inverting versus retaining paradigm for enediyne epoxide hydrolases.

Convocation Year


Convocation Season


Included in

Chemistry Commons