A Systems Biology Approach to Optimisation of (Fed-)Batch and Continuous Fermentation Processes for Recombinant Protein Production

用于优化重组蛋白生产的（补料）分批和连续发酵工艺的系统生物学方法

• 批准号: BB/M028917/1
• 负责人: Gary Black
• 金额: $ 11.24万
• 依托单位: Northumbria University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM028917%2F1
• 关键词: Systems; Biology; Approach; Optimisation; Fed

This project will use a holistic approach that will focus on the complex interactions that give rise to the function and behaviour of a biological system. Specifically, this project will identify a large number of the enzymes and metabolites in the metabolic pathways of Escherichia coli cells, when the bacterium is used as a cell factory to produce large amounts of a recombinant enzyme, i.e. an enzyme produced from a gene that has been introduced into an E. coli cell using Molecular Biology techniques. The holistic approach, known as Systems Biology, will use a combination of two techniques, one to identify the enzymes in the cells, known as proteomics, and the other to identify the metabolites in the cells, known as metabolomics. These techniques require scientific equipment that allow the high resolution (good separation due to the large number of molecules being analysed together) and accurate mass (weight) determination of the enzymes and metabolites (and their components, as the enzymes and metabolites can be broken into fragments for analysis). It is hoped that this holistic approach will allow us to understand the relationships between enzymes and metabolites, external growth factors such as temperature of growth, change of acidity/alkalinity of microbiological growth media as the cells grow, constituents of the microbiological growth media and factors associated with the design of the introduced gene that produces the recombinant enzyme, so that commercial-scale recombinant enzyme production can be improved. Ultimately this would lead to, for example, cheaper more widely available medicines, as many medicines now have to be produced using recombinant enzymes, rather than environmentally unfriendly harsh chemicals.

该项目将采用整体方法，重点关注引起生物系统功能和行为的复杂相互作用。具体而言，本项目将鉴定大肠杆菌细胞代谢途径中的大量酶和代谢物，当细菌用作细胞工厂以生产大量重组酶时，即从已引入大肠杆菌的基因产生的酶。coli细胞中进行细胞培养。这种被称为系统生物学的整体方法将使用两种技术的组合，一种是识别细胞中的酶，称为蛋白质组学，另一种是识别细胞中的代谢物，称为代谢组学。这些技术需要科学设备，以实现酶和代谢物（及其组分，因为酶和代谢物可以分解成碎片进行分析）的高分辨率（由于大量分子一起分析而产生的良好分离）和准确质量（重量）测定。希望这种整体方法将使我们能够理解酶和代谢物之间的关系，外部生长因素如生长温度，随着细胞生长微生物生长培养基的酸碱度变化，微生物生长培养基的成分以及与产生重组酶的引入基因的设计相关的因素，从而可以提高商业规模重组酶生产。最终，这将导致更便宜、更广泛的药物，因为许多药物现在必须使用重组酶而不是对环境有害的刺激性化学品来生产。