Engineering Novel Allosteric Transcription Factor Recognition: Applications in Bio-catalysis and Synthetic Biology

工程新型变构转录因子识别：在生物催化和合成生物学中的应用

• 批准号: 2110033
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2110033
• 关键词: Engineering; Novel; Allosteric; Transcription; Factor

The aim of this project is to explore the potential of engineering transcription factors (TF) with novel allosteric recognition capabilities, and then to apply these novel TFs in the high-throughput selection of new biocatalysts. TFs can be used for a range of applications for example; screening enzymatic processes for biomass valorisation [1], evolving novel enzymes and strains via Adaptive Laboratory Evolution [2], and detection of environmental pollutants and bio-remediation. This project will seek to engineer the recognition properties of MarR-type TFs to recognise alternative aromatic molecules of both natural and synthetic origin [1], and then apply these novel recognition capabilities to evolve enzymes with new substrate tolerance and catalytic performance characteristics. These novel enzymatic and cellular functionalities will provide potential solutions to a number of socioeconomic drivers and environmental demands such as cultural pressure for global sustainability and provide alternative routes for the production of fine-chemicals products and intermediates.The PhD student based in Manchester Institute of Biotechnology will be co-supervised by Dr. Neil Dixon, and Profs David Leys, and Nick Turner, and will be focused on i) engineering MarR-type transcriptional factors to recognise a non-natural aromatic chemicals of environmental and industrial importance, ii) applying the engineered TFs to evolve novel enzymatic functionality and optimise bio-catalytic capability, iii) integrating these individual enzymes and TFs into biosynthetic pathways for whole-cell biotransformation, and iv) using synthetic biology tools and principles to engineer the developed pathway.The student will be trained in broad aspects of biotechnology, microbial gene expression regulation, biocatalysis, directed evolution, microbial fermentation, molecular biology and bio-analytical methods such GC-MS. This project would suit individuals interested in future careers in biotechnology, biocatalysis and bioprocessing.

该项目的目的是探索具有新型变构识别能力的工程转录因子（TF）的潜力，然后将这些新型转录因子应用于新型生物催化剂的高通量选择。 TF 可用于多种应用，例如：筛选生物量增值的酶过程[1]，通过适应性实验室进化进化新型酶和菌株[2]，以及检测环境污染物和生物修复。该项目将寻求设计 MarR 型 TF 的识别特性，以识别天然和合成来源的替代芳香族分子 [1]，然后应用这些新颖的识别能力来进化具有新底物耐受性和催化性能特征的酶。这些新颖的酶和细胞功能将为许多社会经济驱动因素和环境需求（例如全球可持续发展的文化压力）提供潜在的解决方案，并为精细化学品和中间体的生产提供替代途径。曼彻斯特生物技术研究所的博士生将由 Neil Dixon 博士、David Leys 教授和 Nick Turner 共同指导，并将重点关注 i) 工程化 MarR 型转录因子以识别具有环境和工业重要性的非天然芳香族化学物质，ii) 应用工程化的 TF 来进化新的酶功能并优化生物催化能力，iii) 将这些单独的酶和 TF 整合到生物合成途径中以进行全细胞生物转化，以及 iv) 使用合成生物学工具和原理来工程化开发的 学生将接受生物技术、微生物基因表达调控、生物催化、定向进化、微生物发酵、分子生物学和生物分析方法（如 GC-MS）等广泛方面的培训。该项目适合对生物技术、生物催化和生物加工未来职业感兴趣的个人。