Orthogonal Modules Engineered for Synthetic Protein- and Microbial-Networks

专为合成蛋白质和微生物网络设计的正交模块

基本信息

批准号：
EP/N023226/1
负责人：
Mark Howarth
金额：
$ 47.43万
依托单位：
University of Oxford
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FN023226%2F1
关键词：
Orthogonal Modules Engineered Synthetic Protein

项目摘要

Synthetic biology refers to an engineering approach to biology, where biological components can be assembled to function in a controlled and predictable way. Synthetic biology's growing sophistication is likely to generate major changes to society in areas including energy, healthcare and agriculture. Proteins are such powerful tools in synthetic biology because of their diverse structures and activities, including catalysing reactions and sensing changes in the environment. Nowadays engineering of individual proteins is often efficient. Nonetheless proteins usually work together in teams and it is still a major challenge to control how proteins come together into larger assemblies. The problems come from unstable or non-specific links between the different proteins. Our group has established a specific and unbreakable way to connect proteins, from harnessing bacterial protein chemistry. This proposal will adapt this principle, in order to engineer a family of different pairs, where each member of the pair sticks to its partner but does not stick to any other pair. Having such a family of "protein superglues", we will efficiently and stably link multiple proteins to create programmed protein teams. In addition we will harness this linkage technology to connect cells together. Different single-celled organisms often work in partnership in nature and in industrial processes, from fuel production to toxic waste remediation. Engineering these predictable linkages should be a valuable tool underpinning the design of molecular and cellular teams with enhanced cooperation.

合成生物学是指生物学的一种工程方法，其中生物成分可以组装起来以受控和可预测的方式发挥作用。合成生物学的日益成熟可能会在能源、医疗保健和农业等领域给社会带来重大变化。蛋白质因其多样化的结构和活性（包括催化反应和感知环境变化）而成为合成生物学中如此强大的工具。如今，单个蛋白质的工程通常是有效的。尽管如此，蛋白质通常在团队中一起工作，控制蛋白质如何聚集成更大的组件仍然是一个重大挑战。问题来自于不同蛋白质之间不稳定或非特异性的联系。我们的团队通过利用细菌蛋白质化学，建立了一种特定且牢不可破的连接蛋白质的方法。该提案将采用这一原则，以便设计一个由不同配对组成的家庭，其中配对中的每个成员都坚持其伴侣，但不坚持任何其他对。有了这样一个“蛋白质强力胶”家族，我们就能高效、稳定地连接多种蛋白质，形成程序化的蛋白质团队。此外，我们将利用这种连接技术将细胞连接在一起。不同的单细胞生物经常在自然界和工业过程中合作工作，从燃料生产到有毒废物修复。设计这些可预测的联系应该是一个有价值的工具，通过加强合作来支撑分子和细胞团队的设计。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Tunable Extracellular Self-Assembly of Multi-Protein Conjugates from Bacillus subtilis

DOI：
10.1101/087593
发表时间：
2016-11
期刊：
bioRxiv
影响因子：
0
作者：
Charlie Gilbert;M. Howarth;C. Harwood;T. Ellis
通讯作者：
Charlie Gilbert;M. Howarth;C. Harwood;T. Ellis

DogCatcher allows loop-friendly protein-protein ligation.

DOI：
10.1016/j.chembiol.2021.07.005
发表时间：
2022-02-17
期刊：
Cell chemical biology
影响因子：
8.6
作者：
Keeble AH;Yadav VK;Ferla MP;Bauer CC;Chuntharpursat-Bon E;Huang J;Bon RS;Howarth M
通讯作者：
Howarth M

Evolving Accelerated Amidation by SpyTag/SpyCatcher to Analyze Membrane Dynamics.