Author ORCID Identifier

Defense Date


Document Type


Degree Name

Doctor of Philosophy



First Advisor

Dr. Katherine Belecki


As global and political awareness about green and sustainable practices sharpens in the face of dramatic climate change and environmentally detrimental practices, one attractive approach is to harness the catalytic potential of enzymes. Thus influenced, our efforts focused on the development of an innovative chemoenzymatic route to widely prescribed Blockbuster statin drugs, specifically rosuvastatin. In this work, we engineered novel deoxyribose phosphate aldolase (DERA) variants via rationally designed site-directed mutagenesis to accept non-natural, less polar substrate, acrolein, along with acetaldehyde. Several of new mutants displayed elevated tolerance towards aldehydes and showed effective incorporation of acrolein into the unprecedented enzymatically-derived chiral synthon to be deployed in valuable synthetic processes. Olefinic handle introduced by acrolein can be utilized to seamlessly integrate stain heterocyclic core through atom-economic transition-metal (TM) catalysis, olefin cross-metathesis or Heck reaction, compared with wasteful stoichiometric Wittig coupling applied in the current synthetic routes. Fetizon oxidation was employed to obtain lactone product from the enzymatic product, constructing the true side chain of statin. Further with the intention of adaptation into a flow chemistry in future, enzyme immobilization strategy was evaluated. DERA reaction was effectively executed using biocatalyst immobilized on Ni-NTA agarose, for the first time. TM-catalyzed cross-coupling reaction strategies were evaluated for efficient installation of the biocatalytically-prepared chiral side chain onto the heterocyclic core structure. Ultimately, our postulated route in which novel synthons are directly installed to heterocyclic core will represent an effective greener synthetic design which may be extended towards synthesis of other statins, and novel pharmocoactive agents.


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Available for download on Saturday, August 02, 2025