Understanding and Engineering the Nucleation of Enzyme Metal-Organic Frameworks

理解和设计酶金属有机框架的成核

• 批准号: 2102033
• 负责人: Joe Patterson
• 金额: $ 33.92万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2102033&HistoricalAwards=false
• 关键词: Understanding; Engineering; Nucleation; Enzyme; Metal

Enzymes are natural catalysts that can be used by chemical industries to speed up the rate of reactions and reduce the energy requirements of catalytic processes. However, enzymes are not typically stable outside of the physiological environment in which they evolved, significantly limiting their utility for industrial applications. A potential solution to this problem is to immobilize enzymes onto support structures. The ideal support material must be capable of loading high quantities of the active form of the enzyme. The support should also increase the stability and recyclability of the enzyme compared to the free enzyme in solution. Metal-organic frameworks (MOFs) are a promising class of materials for enzyme immobilization. MOFs are porous crystalline materials formed by the self-assembly of metal ions and organic ligands. Enzymes can be immobilized on MOFs by simply mixing the metal, ligand, and enzyme in aqueous solutions at room temperature. The enzymes are then incorporated into the MOF framework during the nucleation and growth processes. Understanding how this process works requires a detailed analysis of the system's nucleation and growth mechanisms. This fundamental mechanistic knowledge will provide robust design rules for the synthesis of enzyme-immobilized MOFs with high loading of the active form of the enzyme. The ability to immobilize practically any enzyme at the MOF surface has the potential to revolutionize the biotechnology industry and benefit society through lower energy chemical processes. The investigator will also develop a mobile K-12 outreach activity that uses low-cost microscopy to observe salt crystal growth. This project aims to determine the nucleation and growth mechanisms of enzyme MOF composite materials. The approach employs cryogenic and liquid-phase electron microscopy. Cryogenic electron microscopy will be used to trap intermediates and analyze their high-resolution structure. Liquid-phase electron microscopy will be used to monitor the kinetics of absorption, nucleation, and growth. The electron microscopy data will be supported by bulk scattering analysis using light and X-rays. The knowledge gained from these mechanistic studies will be used to re-engineer the interfacial chemistry to improve both encapsulation efficiency and enzymatic activity. The project will reveal the formation mechanisms, how the mechanisms can be manipulated by tuning the interfacial chemistry, and the structure-property relationships.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

酶是天然催化剂，化学工业可使用酶来加快反应速率并降低催化过程的能量需求。然而，酶在其进化的生理环境之外通常不稳定，这极大地限制了它们在工业应用中的效用。该问题的一个潜在解决方案是将酶固定在支撑结构上。理想的支撑材料必须能够负载大量活性形式的酶。与溶液中的游离酶相比，载体还应提高酶的稳定性和可回收性。金属有机框架（MOF）是一类很有前景的酶固定化材料。 MOFs是由金属离子和有机配体自组装形成的多孔晶体材料。只需在室温下将金属、配体和酶在水溶液中混合即可将酶固定在 MOF 上。然后，在成核和生长过程中，酶被整合到 MOF 框架中。要了解这个过程的工作原理，需要详细分析系统的成核和生长机制。这一基本机理知识将为合成高负载酶活性形式的酶固定化 MOF 提供稳健的设计规则。将几乎任何酶固定在 MOF 表面的能力有可能彻底改变生物技术行业，并通过较低能耗的化学过程造福社会。研究人员还将开发一种移动 K-12 外展活动，使用低成本显微镜来观察盐晶体的生长。该项目旨在确定酶MOF复合材料的成核和生长机制。该方法采用低温和液相电子显微镜。低温电子显微镜将用于捕获中间体并分析其高分辨率结构。液相电子显微镜将用于监测吸收、成核和生长的动力学。电子显微镜数据将得到使用光和 X 射线的体散射分析的支持。从这些机理研究中获得的知识将用于重新设计界面化学，以提高封装效率和酶活性。该项目将揭示形成机制、如何通过调整界面化学以及结构-性能关系来操纵这些机制。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响进行评估，被认为值得支持审查标准。

项目成果

Role of Molecular Modification and Protein Folding in the Nucleation and Growth of Protein–Metal–Organic Frameworks

分子修饰和蛋白质折叠在蛋白质-金属-有机框架的成核和生长中的作用

• DOI: 10.1021/acs.chemmater.2c01903
• 发表时间: 2022-09-27
• 期刊: Chemistry of Materials
• 影响因子: 8.6
• 作者: Carpenter, Brooke P.;Talosig, A. Rain;Mulvey, Justin T.;Merham, Jovany G.;Esquivel, Jamie;Rose, Ben;Ogata, Alana F.;Fishman, Dmitry A.;Patterson, Joseph P.
• 通讯作者: Patterson, Joseph P.