Enzymes play vital roles in cellular functions by catalyzing biochemical reactions in high activity and selectivity, which is largely attributed to the cooperation between the exquisitely distributed functional groups at the active sites. Reconstruction of the enzymatic active sites in the artificial systems, to produce active and robust biocatalysts, has been a significant but challenging subject. Biomolecular self-assembly, typically with de novo designed peptide or DNA as the building blocks, provides an effective avenue to orient and confine reactive groups into a catalytically active configuration to mimic and even rival the catalytic performance of native enzymes. In this Review, we discuss the chemical and structural properties of DNA and peptide selfassemblies, and principles and strategies of designing active sites that show hydrolase-, peroxidase-, oxidase-, or aldolase-like activities. We focus on the relationship between and control over the structures of the artificial active sites and catalytic performances. We also highlight the synergies between the components in the formation of the active sites, as well as the applications of the artificial enzymes. In the end, we provide an outlook on the obstacles, possible solutions, and future directions, in the aspect of structural modeling, improving catalytic performances, and upgrading complexity of the active sites.
Enzymes fold into unique three-dimensional structures to distribute their reactive amino acid residues, but environmental changes can disrupt their essential folding and lead to irreversible activity loss. The de novo synthesis of enzyme-like active sites is challenging due to the difficulty of replicating the spatial arrangement of functional groups. Here, we present a supramolecular mimetic enzyme formed by self-assembling nucleotides with fluorenylmethyloxycarbonyl (Fmoc)-modified amino acids and copper. This catalyst exhibits catalytic functions akin those of copper cluster-dependent oxidases, and catalytic performance surpasses to date-reported artificial complexes. Our experimental and theoretical results reveal the crucial role of periodic arrangement of amino acid components, enabled by fluorenyl stacking, in forming oxidase-mimetic copper clusters. Nucleotides provide coordination atoms that enhance copper activity by facilitating the formation of a copper-peroxide intermediate. The catalyst shows thermophilic behavior, remaining active up to 95 °C in an aqueous environment. These findings may aid the design of advanced biomimetic catalysts and offer insights into primordial redox enzymes.
Enzymes tend to malfunction when they work out of their natural cellular environments. Engineering a favorable microenvironment around enzymes has emerged as an effective strategy to finely tune the enzymatic functions and reshape the biocatalytic activities. Supramolecular self-assembly provides a bottom-up approach for spatial arrangement of functional groups and fabrication of materials with tailorable local properties. In this review, the progress in designing, creating, and tailoring the enzyme microenvironments is discussed, with the bioinspired self-assembling materials as the scaffolds built from molecular building blocks. The relationship between the physicochemical properties and the local environments (pH, substrates, or hydration) of the scaffolds, and the catalytic properties of the scaffolded enzymes are focused upon. The power of the self-assembly to regulate the catalytic systems dynamically is also highlighted. In the end, an outlook on the obstacles, possible solutions, and future directions on the microenvironment engineering of enzymes is provided.
Photodynamic therapy (PDT) is a light triggered therapy by producing reactive oxygen species (ROS), but traditional PDT may suffer from the real‐time illumination that reduces the compliance of treatment and cause phototoxicity. A supramolecular photoactive G‐quartet based material is reported, which is self‐assembled from guanosine (G) and 4‐formylphenylboronic acid/1,8‐diaminooctane, with incorporation of riboflavin as a photocatalyst to the G4 nanowire, for post‐irradiation photodynamic antibacterial therapy. The G4‐materials, which exhibit hydrogel‐like properties, provide a scaffold for loading riboflavin, and the reductant guanosine for the riboflavin for phototriggered production of the therapeutic H2O2. The photocatalytic activity shows great tolerance against room temperature storage and heating/cooling treatments. The riboflavin‐loaded G4 hydrogels, after photo‐irradiation, are capable of killing gram‐positive bacteria (e.g., Staphylococcus aureus), gram‐negative bacteria (e.g., Escherichia coli), and multidrug resistant bacteria (methicillin‐resistant Staphylococcus aureus) with sterilization ratio over 99.999%. The post‐irradiated hydrogels also exhibit great antibacterial activity in the infected wound of the rats, revealing the potential of this novel concept in the light therapy.
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