Engineering spatial segregation within bacterial hosts for bio-therapeutic protein production

在细菌宿主内设计空间分离以生产生物治疗蛋白质

基本信息

批准号：
1974411
负责人：
金额：
--
依托单位：
University College London
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1974411
关键词：
Engineering spatial segregation within bacterial

项目摘要

The production of bio-therapeutic proteins of industrial interest in recombinant hosts is becoming an increasingly popular alternative to production in mammalian cell culture which can be slow and expensive. The overall aim of this project is to develop a bacterial system for recombinant protein production by engineering compartmentalisation within the cytoplasm of E. coli which may allow for an environment that promotes production and purification of post-translationally modified proteins. In nature, compartmentalisation is achieved by localising enzymes inside of sophisticated proteinaceous organelles called bacterial microcompartments (BMCs). In the past decade, significant progress has been made to engineer these BMCs, to permit the construction of synthetic microcompartments within the bacterial cell. In this project the potential of these structures to be used for the production and purification of recombinant proteins is explored.The project will expand our understanding of the fundamentals of engineering synthetic compartmentalisation, the benefits and limitations of protein compartmentalisation and inform the rational design of future microcompartment-derived technologies. The project is aligned with the EPSRC centre for Doctoral Training in Bioprocess Engineering Leadership. It provides new synthetic biology approaches to the redesign of cellular chemistry and will impact in the development of cost-effective and sustainable bio-based manufacture.

在重组宿主中生产具有工业意义的生物治疗蛋白正成为一种日益流行的替代哺乳动物细胞培养生产的方法，后者可能缓慢且昂贵。该项目的总体目标是通过在大肠杆菌细胞质内进行工程划分来开发用于重组蛋白生产的细菌系统，这可能会创造一个促进翻译后修饰蛋白的生产和纯化的环境。在自然界中，区室化是通过将酶定位在称为细菌微区室 (BMC) 的复杂蛋白质细胞器内来实现的。在过去的十年中，这些 BMC 的工程化取得了重大进展，以允许在细菌细胞内构建合成微区室。在这个项目中，探索了这些结构用于重组蛋白生产和纯化的潜力。该项目将扩大我们对工程合成区室化基础知识、蛋白质区室化的好处和局限性的理解，并为未来的合理设计提供信息。微室衍生技术。该项目与 EPSRC 生物过程工程领导力博士培训中心保持一致。它为细胞化学的重新设计提供了新的合成生物学方法，并将影响具有成本效益和可持续的生物基制造的发展。