Enzyme catalysis incorporated into pharmaceutical or chemical manufacturing can be environmentally more friendly and efficient than traditional synthesis with solely organic and inorganic reagents. Chemical conjugation of DNA, protein, or polymer scaffolds to an enzyme is a widely used strategy to enhance enzyme stability and activity. A central challenge in the design of such systems is a fundamental understanding of the effects of scaffold position on the desired enzyme property. In cells, colocalized multistep enzymatic reaction pathways within biological catabolic and metabolic processes occur with high yield and specificity. Therefore, applying similar strategies as what the nature has evolved may lead to enhanced overall rates of final product synthesis. Spatial organization on membranes, surfaces or various confirmed space can be associated with increased efficiency of intermediate substrate transfer. In this presentation, we will talk about using a combined computational and experimental approach to develop and validate a predictive model for biocatalytic activity enhancement. We will discuss a significant advantage in catalytic enhancement by optimizing the scaffold colocalized, which also provides the intermediate a diffusive advantage that enhanced substrate transfer probability. We also show that the substrate concentration can be increased locally by chemical conjugation of DNAs which also contributes to overall rate enhancement. The results highlight the importance of the non-specific intermolecular attractions and effective substrate concentration in catalysis. They shed light on strategies for engineering multienzyme and/or conjugated nanostructures for various applications.

Multiscale simulation-guided enzyme nanostructure design for catalysis enhancement: effective substrate concentration, scaffolds, and spatial organization

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.