Controlled Self-Assembly of the Catalytic Core of Hydrolases Using DNA Scaffolds

Precisely organizing functional molecules of the catalytic cores in natural enzymes to promote catalytic performance is a challenging goal in respect to artificial enzyme construction. In this work, we report a DNA-scaffolded mimicry of the catalytic cores of hydrolases, which showed a controllable and hierarchical acceleration of the hydrolysis of fluorescein diacetate (FDA). The results revealed that the efficiency of hydrolysis was greatly increased by the DNA-scaffold-induced proximity of catalytic amino acid residues (histidine and arginine) with up to 4-fold improvement relative to the free amino acids. In addition, DNA-scaffolded one-dimensional and two-dimensional assemblies of multiple catalytic cores could further accelerate the hydrolysis. This work demonstrated that the DNA-guided assembly could be used as a promising platform to build enzyme mimics in a programmable and hierarchical way.

Automated summary

In this work, a DNA-scaffolded mimicry of the catalytic cores of hydrolases is reported, showing controllable and hierarchical acceleration of the hydrolysis of fluorescein diacetate (FDA). The study demonstrates that the efficiency of hydrolysis is greatly increased by the proximity of catalytic amino acid residues induced by the DNA scaffold, with up to 4-fold improvement compared to free amino acids. Additionally, one-dimensional and two-dimensional assemblies of multiple catalytic cores further enhance the hydrolysis. This work highlights the potential of DNA-guided assembly as a promising platform for constructing enzyme mimics in a programmable and hierarchical manner.