Enhancing enzymatic activity with nanoparticle display – an updated compendium and engineering outlook

Almost all utilization of biocatalysis in the burgeoning field of synthetic biology requires not only enzymes but also that they function with peak efficiency, especially when paired with other enzymes in designer multistep cascades. This has driven concerted efforts into enhancing enzymatic performance by attaching them to macroscale scaffolding materials for display. Although providing for improved long-term stability, this attachment typically comes at the cost of decreased catalytic efficiency. However, an accumulating body of data has confirmed that attaching enzymes to various types of nanoparticle (NP) materials can often dramatically increase their catalytic efficiency. Many of the causative mechanisms that give rise to such enhancement remain mostly unknown but it is clear that the unique structured and interfacial environment that physically surrounds the NP material is a major contributor. In this review, we provide an updated and succinct overview of the current understanding and key factors that contribute to enzymatic enhancement by NP materials including the unique structured NP interfacial environment, NP surface chemistry and size, and the influence of bioconjugation chemistry along with enzyme mechanics. We then provide a detailed listing of examples where enzymes have displayed enhanced activity of some form when they are displayed on a NP as organized by material types such as semiconductor quantum dots, metallic NPs, DNA nanostructures, and other more non-specific and polymeric nanomaterials. This is followed by a description of what has been learned about enhancement from these examples. We conclude by discussing what more is needed for this phenomenon to be exploited and potentially translated in the design and engineering of far more complex molecular systems and downstream applications.