259938 DFT Characterization of the Hydrolysis of β-1,4 Glycosidic Bonds
The glycoside hydrolase reaction is a key step in breaking down polysaccharides. Once it is broken down into simple sugars, monomers can be used in fermentation and other catalytic processing steps . Unfortunately, this is a costly process because of the complex reaction pathway, and requires a catalyst to occur efficiently. Lowering the cost of enzymatic biopolymer decomposition is a longstanding engineering goal, which could greatly improve the economics of these processes.
To gain more insight into the catalytic mechanism, we have used DFT to determine the relevant transition states and intermediates for the complete reaction pathway of the hydrolysis of the β-1,4 glycosidic bond. Structures were optimized at the B3LYP/6-31+G(d,p) level of theory both in vacuum and in a continuum solvation model in water using Gaussian 09 . These calculations were done with a generic six-carbon sugar dimer, and repeated with cellobiose dimer and xylose dimer models. The entire glycoside hydrolase reaction pathway is comprised of two transition states and one metastable intermediate. From the optimized structures, an energy landscape was constructed for each system. A continuum solvation model was applied, and observed to decrease both transition state barriers 4-10 kcal/mol. The overall barrier height is 24.3 kcal/mol for the generic model. The impact of the enzyme environment in creating catalytic properties is examined by comparing these results to the uncatalyzed reaction using water and hydroxide ions.
A kinetic analysis with Campbell’s degree of rate control is used to study the relative importance of the intermediates and two barrier heights. We have also studied the effect of the model amino acid groups in the reaction pathway and developed quantitative structure-property relationships that relate the energetics and structures.
 Dodd and Cann. Enzymatic deconstruction of xylan for biofuel production. GCB Bioenergy (2009) vol. 1 (1) pp. 2-17
 Frisch, M. J., et al. 2009. Gaussian 09, Revision A.1. Gaussian, Inc., Wallingford, CT.