Nguyen, Bach2024-01-052024-01-052023-10https://hdl.handle.net/11299/259621University of Minnesota Ph.D. dissertation. October 2023. Major: Chemical Physics. Advisor: Jiali Gao. 1 computer file (PDF); xiii, 162 pages.Decarboxylation reactions and its reversal – carboxylation – are wide-spread in chemistry and biology, which play a key role in the metabolic cycle of carbon-based lifeforms. In nature, the bulk of biologically produced CO2 are the product of fermentation and respiration including the decarboxylation of organic acids. This thesis is dedicated to the understanding of enzymatic decarboxylation mechanisms through the use of dual level quantum mechanics/molecular mechanics calculations.In chapter 2, the barrier to decarboxylation in the aqueous phase was explored to reveal that the barrier for CO2 capture corresponding to the reverse decarboxylation reaction is fully induced by solvent effects, especially in aqueous solution. In chapter 3, we determined that the decarboxylation mechanism of 5caU, highlighting the mechanistic differences with 6caU decarboxylation. In chapter 4, we investigated the decarboxylation mechanism of 5caU in IDCase, highlighting the different contributing factors towards the rate improvements. Finally, in chapter 5, we investigated the mechanism of prFMN-catalyzed decarboxylation of FDCA, including the elucidation of the protonation state of prFMN as well as created a basis towards the reverse engineering of UbiD.enThesis or Dissertation