Praseodymium doped cerium oxide nanozyme as a functional analog of topoisomerase I

Abstract

Topoisomerases are essential hydrolases that facilitate the topological rearrangement of DNA by cleaving nucleic acid strands. Specifically, topoisomerase I (TOPO I) enhances DNA transcription by introducing single-strand breaks in the DNA double helix, relaxing supercoiled DNA, and catalyzing the subsequent re-ligation of the cleavage sites. However, the intricate catalytic mechanism of TOPO I has posed significant challenges for developing effective enzymatic mimics. Here, we demonstrate that praseodymium-doped cerium oxide nanoparticles (CeO₂:Pr³⁺) exhibit the TOPO I-like catalytic activity, mediating the topological rearrangement of supercoiled DNA. CeO₂:Pr³⁺ nanoparticles act as functional analog of TOPO I enzyme, catalyzing the transition of plasmid DNA from a supercoiled to a nicked open circular configuration compared to undoped CeO₂ nanoparticles. Mechanistic studies revealed that Pr³⁺ doping enhances Ce(III) activity by replacing Ce-bound hydroxide, a weak nucleophile, thereby facilitating phosphodiester bond cleavage. This modification improves substrate turnover rates and higher catalytic efficiency at low substrate concentrations. These findings underscore the potential of Pr³⁺ doping to advance the design of enzyme with similar functional activity for industrial and laboratory applications requiring efficient nucleic acid manipulation.