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

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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.