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Engineering biocatalytic nanoreactor

工程生物催化纳米反应器

基本信息

批准号：
1706891
负责人：
Stefan Lutz
金额：
$ 35.46万
依托单位：
Emory University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2020-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1706891&HistoricalAwards=false
关键词：
Engineering biocatalytic nanoreactor

项目摘要

Compartmentalization is a critical component of cellular function, enabling a multitude of biochemical reactions to occur at specific location in the cell at specific times. Reproducing such performance with one or more biological and chemical catalysts in the lab and in industry offers tremendous opportunities for future developments of green and sustainable chemical processes. The proposed project draws inspiration from nature by exploring bacterial "capsules" as containers for the orderly immobilization of catalysts. The capsules are nanometer-scale, hollow spheres with protein shells that assemble spontaneously. Protein engineering strategies will be explored to tailor these nanostructures to the specific reaction sequences of interest. The goals are to improve the selective passage of raw materials through the shell, and to reproducibly "decorate" the interior side of the shell with specific reaction catalysts. In combination, these efforts will produce engineered nano-scale reactor vessels that can be designed to perform a variety of industrially interesting reaction sequences. There will also be STEM career development efforts that will involve students from K-12 through college age. These include Science Days at an elementary school, protein modeling competitions for local high school students, undergraduate research experiences, and protein design and 3D printing activities at the Annual Atlanta Science Festival.The project will explore the impact of catalytic performance of (bio) catalysts upon encapsulation in and controlled surface-immobilization on protein-based encapsulin nanocompartments. Protein engineering strategies ranging from random mutagenesis and incremental truncation to protein design will be employed to remodel nanocompartments for enhanced substrate and product permeability and to create new opportunities for functional diversification via artificial affinity sites on the encapsulin surfaces. Beyond single particles, the assembly of nanocompartments into multi-dimensional nanoreactor assemblies for high-density biocatalyst systems will be explored. Using a combination of biophysical methods, as well as biocatalytic and biosensory systems, the impact of these engineering efforts on the structure of nanocompartments themselves and the function of the associated catalysts will be assessed. By integrating design parameters into this system that offer the potential for high enantioselectivity and reduced separation costs, this technology would have significant implications for therapeutic drug development.

区室化是细胞功能的关键组成部分，使许多生化反应在特定时间在细胞的特定位置发生。在实验室和工业中用一种或多种生物和化学催化剂再现这样的性能为绿色和可持续化学工艺的未来发展提供了巨大的机会。拟议的项目从自然界中汲取灵感，探索细菌“胶囊”作为有序固定催化剂的容器。这些胶囊是纳米级的中空球体，带有自发组装的蛋白质外壳。将探讨蛋白质工程策略，以定制这些纳米结构的特定反应序列的利益。目标是提高原料通过壳的选择性，并用特定的反应催化剂可重复地“装饰”壳的内侧。结合起来，这些努力将产生工程纳米级反应器容器，可以设计用于执行各种工业上感兴趣的反应序列。还将有STEM职业发展工作，将涉及从K-12到大学年龄的学生。其中包括在一所小学的科学日，为当地高中生举办的蛋白质建模比赛，本科生的研究体验，以及在年度亚特兰大科学节上的蛋白质设计和3D打印活动。该项目将探索（生物）催化剂的催化性能对纳米隔室中基于蛋白质的纳米隔室的封装和受控表面固定的影响。从随机诱变和增量截短到蛋白质设计的蛋白质工程策略将用于重塑纳米室，以增强底物和产品的渗透性，并通过人工亲和位点在蛋白质表面上为功能多样化创造新的机会。除了单个粒子，将探索将纳米室组装成用于高密度生物催化剂系统的多维纳米反应器组件。使用生物物理方法的组合，以及生物催化和生物传感系统，这些工程努力对纳米区室本身的结构和相关催化剂的功能的影响将进行评估。通过将设计参数整合到该系统中，提供了高对映体选择性和降低分离成本的潜力，该技术将对治疗药物开发产生重大影响。