Because of the high catalytic activities and substrate specificity, natural enzymes have been widely used in industrial, medical, and biological fields, etc. Although promising, they often suffer from intrinsic shortcomings such as high cost, low operational stability, and difficulties of recycling. To overcome these shortcomings, researchers have been devoted to the exploration of artificial enzyme mimics for a long time. Since the discovery of ferromagnetic nanoparticles with intrinsic horseradish peroxidase-like activity in 2007, a large amount of studies on nanozymes have been constantly emerging in the next decade. Nanozymes are one kind of nanomaterials with enzymatic catalytic properties. Compared with natural enzymes, nanozymes have the advantages such as low cost, high stability and durability, which have been widely used in industrial, medical, and biological fields. A thorough understanding of the possible catalytic mechanisms will contribute to the development of novel and high-efficient nanozymes, and the rational regulations of the activities of nanozymes are of great significance. In this review, we systematically introduce the classification, catalytic mechanism, activity regulation as well as recent research progress of nanozymes in the field of biosensing, environmental protection, and disease treatments, etc. in the past years. We also propose the current challenges of nanozymes as well as their future research focus. We anticipate this review may be of significance for the field to understand the properties of nanozymes and the development of novel nanomaterials with enzyme mimicking activities.

Nanozymes: Classification, Catalytic Mechanisms, Activity Regulation, and Applications

As a new generation of artificial enzymes, nanozymes have the advantages of high catalytic activity, good stability, low cost, and other unique properties of nanomaterials. Due to their wide range of potential applications, they have become an emerging field bridging nanotechnology and biology, attracting researchers in various fields to design and synthesize highly catalytically active nanozymes. However, the thorough understanding of experimental phenomena and the mechanisms beneath practical applications of nanozymes limits their rapid development. Herein, the progress of experimental and computational research of nanozymes on two issues over the past decade is briefly reviewed: (1) experimental development of new nanozymes mimicking different types of enzymes. This covers their structures and applications ranging from biosensing and bioimaging to therapeutics and environmental protection. (2) The catalytic mechanism proposed by experimental and theoretical study. The challenges and future directions of computational research in this field are also discussed.

Recent Advances in Nanozyme Research

Emerging nanocatalytic tumor therapies based on nontoxic but catalytically active inorganic nanoparticles (NPs) for intratumoral production of high-toxic reactive oxygen species have inspired great research interest in the scientific community. Nanozymes exhibiting natural enzyme-mimicking catalytic activities have been extensively explored in biomedicine, mostly in biomolecular detection, yet much fewer researches are available on specific nanocatalytic tumor therapy. This study reports on the construction of an efficient biomimetic dual inorganic nanozyme-based nanoplatform, which triggers cascade catalytic reactions for tumor microenvironment responsive nanocatalytic tumor therapy based on ultrasmall Au and Fe3O4 NPs coloaded dendritic mesoporous silica NPs. Au NPs as the unique glucose oxidase-mimic nanozyme specifically catalyze β-D-glucose oxidation into gluconic acid and H2O2, while the as produced H2O2 is subsequently catalyzed by the peroxidase-mimic Fe3O4 NPs to liberate high-toxic hydroxyl radicals for inducing tumor-cell death by the typical Fenton-based catalytic reaction. Extensive in vitro and in vivo evaluations have demonstrated high nanocatalytic-therapeutic efficacy with a desirable tumor-suppression rate (69.08%) based on these biocompatible composite nanocatalysts. Therefore, this work paves a way for nanocatalytic tumor therapy by rationally designing inorganic nanozymes with multienzymatic activities for achieving high therapeutic efficacy and excellent biosafety simultaneously.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/advs.201801733

Nanocatalytic Tumor Therapy by Biomimetic Dual Inorganic Nanozyme-Catalyzed Cascade Reaction.

Bacterial infection is one of the top ten leading causes of death globally and the worst killer in low-income countries. The overuse of antibiotics leads to ever-increasing antibiotic resistance, posing a severe threat to human health. Recent advances in nanotechnology provide new opportunities to address the challenges in bacterial infection by killing germs without using antibiotics. Antibiotic-free antibacterial strategies enabled by advanced nanomaterials are presented. Nanomaterials are classified on the basis of their mode of action: nanomaterials with intrinsic or light-mediated bactericidal properties and others that serve as vehicles for the delivery of natural antibacterial compounds. Specific attention is given to antibacterial mechanisms and the structure-performance relationship. Practical antibacterial applications employing these antibiotic-free strategies are also introduced. Current challenges in this field and future perspectives are presented to stimulate new technologies and their translation to fight against bacterial infection.

https://espace.library.uq.edu.au/view/UQ:83fdbcc/UQ83fdbcc_OA.pdf

Antibiotic-Free Antibacterial Strategies Enabled by Nanomaterials: Progress and Perspectives.

Highly-efficient and eco-friendly materials and technologies are urgently needed to meet the requirements of nowadays green development. Photocatalysis with using solar energy and enzymatic catalysis with eco-friendly nature are effective alternatives to address the problem. Notably, beneficial use of the synergistic effect of artificial enzyme and advanced photocatalyst has attracted wide attention. This work presents a biomimetic photocatalytic material, two-dimensional (2D) biomimetic hemin-bismuth tungstate (HBWO). Stable HBWO composites formed by immobilization of monomeric hemin on 2D bismuth tungstate layer, exhibit high photocatalytic performance, better than that of pure 2D bismuth tungstate and unsupported hemin. HBWO shows layered structure with the interlayer spacing at ˜0.35 nm. In the photocatalytic process, hemin can not only act as an electron shuttle, also play an important role in oxygen transfer. Additionally, the synthesized HBWO composites exhibit nice binding affinities and high photocatalytic activity in tetracycline degradation. It is anticipated that beneficial use of synergistic effect of artificial enzyme and photocatalyst via HBWO composites can be a promising eco-friendly and efficient solution for addressing the environmental crisis.

Synergistic effect of artificial enzyme and 2D nano-structured Bi2WO6 for eco-friendly and efficient biomimetic photocatalysis

Carbon nanotubes (CNTs) and their derivatives have emerged as a series of efficient biocatalysts to mimic the function of natural enzymes in recent years. However, the unsatisfiable enzymatic efficiency usually limits their practical usage ranging from materials science to biotechnology. Here, for the first time, we present the synthesis of several oxygenated-group-enriched carbon nanotubes (o-CNTs) via a facile but green approach, as well as their usage as high-performance peroxidase mimics for biocatalytic reaction. Exhaustive characterizations of the enzymatic activity of o-CNTs have been provided by exploring the accurate effect of various oxygenated groups on their surface including carbonyl, carboxyl, and hydroxyl groups. Because of the “competitive inhibition” effect among all of these oxygenated groups, the catalytic efficiency of o-CNTs is significantly enhanced by weakening the presence of noncatalytic sites. Furthermore, the admirable enzymatic activity of these o-CNTs has been successfully app...

Unraveling the Enzymatic Activity of Oxygenated Carbon Nanotubes and Their Application in the Treatment of Bacterial Infections

The degradation of recalcitrant polysaccharides such as cellulose and chitin requires the synergistic functionality of processive glycosidase (GH) cocktails. Understanding the fundamental phenomenon of processivity is of biological and economic importance for the conversion of biomass into biofuel. In this work, cellulase family 9 from Clostridium cellulovorans (Cel9G), which is a processive endoglucanase, was used to elucidate the processive binding mechanism with respect to polysaccharides, since it exhibits a multimodular crystallographic structure. Metadynamics and molecular dynamics simulations were performed to explore the dynamics of cellulose chain binding to Cel9G via processive motion. The processive movement of the cellulose chain towards the catalytic domain may exhibit several local minima, which are related to strong CH/π interactions between the sugar rings and the aromatic residues distributed at the active site. For the binding of the G6 and G12 molecules, the energy barriers were determined to be 4.8 and 7.4 kcal mol-1, respectively. Based on the site-directed mutagenesis simulations of Y520A, it was found that the existence of Y520 is critical for processive binding. It is likely that Y520 and H125/Y416 form two anchor points to facilitate processive binding to polysaccharides. More importantly, the straight-line morphology of the substrate could be observed after the formation of the so-called slide mode, which is different from the V-shaped Michaelis complex structure revealed by quantum mechanics/molecular mechanics simulations. This indicates that an additional step, namely, catalytic activation, probably exists between processive binding and the hydrolysis reaction. Finally, a four-step catalytic cycle was proposed for Cel9G. Our work provides novel molecular-level insights into the structure-function relationship for the processive enzyme Cel9G and should aid the development of improved GH cocktails for the efficient cleavage of glycosidic linkages.

Processive binding mechanism of Cel9G from Clostridium cellulovorans: molecular dynamics and free energy landscape investigations.

WO_x/C Heterogeneous Catalyst with Oxygen Vacancies and Deficient Brönsted Acid for Epoxidation of 1-Hexene

Carbohydrate degradation catalyzed by glucoside hydrolases (GHs) is a major mechanism in biomass conversion. GH family 9 endoglucanase (Cel9G) from Clostridium cellulovorans, a typical multimodular enzyme, contains a catalytic domain closely linked to a family 3c carbohydrate-binding module (CBM3c). Unlike the conventional behavior proposed for other carbohydrate-binding modules, CBM3c has a direct impact on catalytic activity. In this work, extensive molecular dynamics (MD) simulations were employed to clarify the functional role of CBM3c. Furthermore, the detailed catalytic mechanism of Cel9G was investigated at the atomistic level using the combined quantum mechanical and molecular mechanical (QM/MM) method. Based on these simulations, owing to the rigidity of the peptide linker, CBM3c may affect the enzymatic activity via direct interactions with alpha helix 4 of GH9, especially with the K123 and H125 residues. In addition, using cellohexaose as a substrate, the QM/MM MD simulations confirmed that this enzyme can cleave the β-1,4-glycosidic linkage via an inverting mechanism. An oxocarbenium ion-like transition state was located with a barrier height of 19.6 kcal mol-1. Furthermore, the G(-1) pyranose unit preferentially adopted a distorted 1S5/4H5 conformer in the enzyme-substrate complex. For the cleavage of the glycosidic bond, we were able to identify a plausible route (1S5/4H5 → [4H5/4E]# → 4C1) from the reactant to the product at the G(-1) site.

Penghui Li

Papers

Unraveling the Enzymatic Activity of Oxygenated Carbon Nanotubes and Their Application in the Treatment of Bacterial Infections

Processive binding mechanism of Cel9G from Clostridium cellulovorans: molecular dynamics and free energy landscape investigations.

WO_x/C Heterogeneous Catalyst with Oxygen Vacancies and Deficient Brönsted Acid for Epoxidation of 1-Hexene

QM/MM investigation of the catalytic mechanism of processive endoglucanase Cel9G from Clostridium cellulovorans.

Insights into the effect of oxygen vacancies on the epoxidation of 1-hexene with hydrogen peroxide over WO3−x/SBA-15