用于工程酶仿生材料的多分子组件自组装

IF 14 Q1 CHEMISTRY, MULTIDISCIPLINARY
Shichao Xu, Yuanxi Liu, Baoli Zhang, Shan Li, Xiangyu Ye and Zhen-Gang Wang*, 
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引用次数: 0

摘要

天然酶具有复杂的三维结构,能以超乎寻常的精度和速度促进各种生化反应。酶的催化能力源于其活性位点的独特结构,在活性位点上,功能基团与辅助因子(有机或离子)协作或辅助,特异性地结合底物并催化转化。受酶的结构-功能关系启发,超分子自组装这种自下而上的纳米制造方法已被用于制造仿酶催化剂。然而,准确复制酶的活性位点是一项艰巨的挑战,这主要是因为模仿天然蛋白质折叠的复杂性错综复杂。许多天然生物系统,如色氨酸合成酶或核糖体,都依赖于多个亚基的结合,每个亚基都保持其结构的完整性,从而实现高效和多功能的功能。在这些系统中观察到的分层自组装原理启发我们设计和自组装互补分子构件,形成单独的折叠或聚集结构,从而精确控制活性基团的分布,创建类似酶的活性位点。在不破坏折叠结构的情况下定制其中任何一种成分,都可以灵活地设计催化特性。本研究将利用我们实验室的研究进展,主要侧重于利用多种分子成分的自组装,构建具有内置金属依赖性或无金属活性位点的仿酶催化剂。为了在合成材料中制造依赖金属的酶位点(如血红素口袋或铜位点),我们创建了一个超分子支架来稳定血红素或形成铜簇,然后引入第二种成分来增强底物吸附或金属反应性。由此产生的酶模拟物具有显著的协同催化活性,并在高温、高离子强度和循环酸化/中和处理等苛刻条件下具有极高的稳定性。它们可以被设计成对特定手性或尺寸的底物具有可定制的选择性,并可在外部刺激下在 ON/OFF 状态之间切换。这些模拟物在相关生物大分子的传感、生物质降解以及帮助了解原生酶的催化机理方面表现出了卓越的性能。为了实现无金属催化,我们在催化元件中引入了 "驱动 "元件,以引导模仿水解酶、光脱羧酶或光氧化物酶活性的组装体的形成,并将其应用于肽修饰或抗菌治疗。此外,组氨酸等有组织成分可以催化依赖血红素的酶所实现的反应,为新型生物催化机理提供了启示。最后,我们讨论了与结构建模、提高催化性能和增加活性位点复杂性有关的关键挑战。最后,我们讨论了与结构建模、提高催化性能和增加活性位点复杂性有关的关键挑战,并提出了实现高价值实际应用的未来展望。我们的共同努力勾勒出了开发稳健的仿酶催化剂的策略,这些通用方法可扩展到其他旨在仿酶催化的超分子系统。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Self-Assembly of Multimolecular Components for Engineering Enzyme-Mimetic Materials

Self-Assembly of Multimolecular Components for Engineering Enzyme-Mimetic Materials

Natural enzymes, with their intricate three-dimensional structures, facilitate a wide array of biochemical reactions with exceptional precision and speed. The catalytic capabilities of enzymes arise from the distinctive structures of their active sites, where functional groups collaborate or aid cofactors (organic or ionic) in binding substrates with specificity and catalyzing transformations. Inspired by the structure–function relationship of enzymes, supramolecular self-assembly, a bottom-up approach in nanofabrication, has been employed to create enzyme-mimetic catalysts. However, accurately replicating enzymatic active sites poses a formidable challenge, primarily because of the intricacies in mimicking the complexity of natural protein folding.

Many natural biological systems, such as tryptophan synthase or ribosomes, rely on the association of multiple component subunits, each maintaining its structural integrity, to enable efficient and versatile functionalities. The hierarchical self-assembly principles observed in these systems have inspired us to design and self-assemble complementary molecular building blocks that form individual folding or aggregating structures, allowing for precise control over the distribution of reactive groups to create enzyme-like active sites. The customization of either component without disrupting folding structures enables the flexible engineering of catalytic properties. This Account will primarily focus on employing the self-assembly of multiple molecular components, drawing from research progress in our lab, to construct enzyme-mimetic catalysts with built-in metal-dependent or metal-free active sites. The structure–function relationship of these catalysts will be highlighted.

To fabricate metal-dependent enzymatic sites, such as heme pockets or copper sites, within the synthetic materials, we create a supramolecular scaffold for stabilizing hemin or forming a copper cluster, followed by the introduction of a second component to enhance substrate adsorption or metal reactivity. The resulting enzyme mimics exhibit remarkable synergistic catalytic activities and possess great stability against the harsh conditions, such as high temperatures, high ionic strength, and cyclic acidification/neutralization treatment. They can be engineered to possess tailorable selectivity toward specific chirality or sizes of substrates and can be externally stimulated to switch between ON/OFF states. These mimics have shown great performances in the sensing of biomolecules of interest, biomass degradation, and aiding in the understanding of the catalytic mechanism of native enzymes. To achieve metal-free catalysis, we introduce a “driving” component to the catalytic component to guide the formation of the assemblies mimicking the activity of hydrolases, photodecarboxylase, or photo-oxidase, with applications in peptide modifications or antibacterial therapy. Moreover, organized components like histidine can catalyze the reactions achieved by heme-dependent enzymes, providing insights into novel biocatalytic mechanisms. Additionally, we discuss the self-assembly of DNAzyme units with DNA nanostructured templates, which provide suitable microenvironments to facilitate the fabrication of the polymer nanopattern with well-defined shapes.

In the end, we discuss the key challenges related to structural modeling, enhancing catalytic performance, and increasing the complexity of active sites. We also propose future perspectives for achieving high-value practical applications. Our collective efforts outline strategies for developing robust enzyme-mimetic catalysts, and these general methods may extend to other supramolecular systems aiming to mimic enzymatic catalysis.

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CiteScore
17.70
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