Work

Enhancing Enzyme Activity Via Noncovalent Association with DNA-Functionalized Nanoparticles

Year: 2026

Type: article

Abstract: Enhancing enzyme performance without protein engineering remains a central challenge in biocatalysis. Here, we report the unusual discovery that nanoparticles densely functionalized with DNA, commonly known as spherical nucleic acids (SNAs), can bind enzymes without chemical conjugation, affinity tags, or engineered recognition motifs and substantially increase catalytic activity. Using cytochrome c as a model peroxidase, we show that noncovalent binding to SNAs increases the apparent turnover number by up to 15-fold. Mechanistic studies by varying DNA density, length, and nanoparticle core identity reveal that activity enhancement does not arise from free DNA or the nanoparticle core alone but from the three-dimensional, high-density presentation of DNA at the nanoparticle surface. Consequently, similar effects are observed when gold cores are replaced with glucose oxidase or antibody cores. Moreover, activity modulation also depends on DNA sequence, establishing sequence design as a programmable handle for tuning enzyme output. All-atom molecular dynamics simulations, binding studies, and circular dichroism further reveal that base-specific interactions reshape enzyme conformational flexibility and increase active-site accessibility. This effect generalizes beyond cytochrome c to catalase and carbonic anhydrase. Together, these findings establish SNAs as adaptable, sequence-programmable platforms for enhancing and coordinating biocatalysis and expand their functional scope into enzyme regulation.

Source: JACS Au

DOI: 10.1021/jacsau.6c00921