Develop Spatially‐ Interactive Multienzyme Complex on Selfassembled DNA Nanostructures

Abstract

Cellular activities are directed by complex, multi‐step synthetic pathways. Many of the enzymes in these pathways are spatially organized to improve both the speed and specificity. This abstracts presents a DNA scaffold‐directed strategy to assemble multienzyme systems with precisely controlled orientations and positions. It has increased our understanding of the enzymology for biological metabolic pathways and also provided the tools and design principles for creating efficient man‐made catalytic complexes.As shown in Figure 1, a two‐enzyme Glucose Oxidase (GOx) ‐ Horseradish Peroxidase (HRP) cascade was assembled on rectangular DNA origami tiles with inter‐enzyme distances ranging from 10 to 65 nm. It was observed that the rate of coupled reactions dramatically increased when the two enzymes were positioned very close together (e.g. 10‐nm in Figure 1B) so that the hydration shells of enzymes overlapped. Further, a protein bridge structure was constructed to facilitate the transfer of intermediates between enzymes (Figure 1C). This opens the door for the design of much more efficient multi‐enzyme systems which should find utility in the development of catalysts for the production of high‐value products in industry and bioenergy, as well as diagnostic applications in biomedicine.