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

本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TF应用于新型生物催化剂的高通量选择。tf可用于一系列应用，例如；筛选生物质增值的酶促过程[1]，通过适应性实验室进化[2]进化新的酶和菌株[2]，以及环境污染物检测和生物修复。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[1]的替代芳香分子，然后应用这些新的识别能力来进化具有新的底物耐受性和催化性能特征的酶。这些新的酶和细胞功能将为许多社会经济驱动因素和环境需求（如全球可持续性的文化压力）提供潜在的解决方案，并为精细化工产品和中间体的生产提供替代途径。这位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教授共同指导，并将专注于i)工程marr型转录因子，以识别对环境和工业具有重要意义的非天然芳香化学物质，ii)应用工程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整合到全细胞生物转化的生物合成途径中，iv)使用合成生物学工具和原理来设计已开发的途径。学生将在生物技术、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）等广泛方面接受培训。本项目适合对未来生物技术、生物催化和生物加工领域感兴趣的个人。

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.