Understanding and exploiting bacterial sugar transporters for increased production of human prebiotics

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The production of prebiotic compounds like human milk oligosaccharides (HMOs) is a valuable and expanding market for industrial biotechnology. Bacterial cells make and break oligosaccharides during many processes and engineered strains of the bacterium Escherichia coli can synthesize human-like HMOs in the cytoplasm. While optimizing the production of these products, it is apparent that product export is a bottleneck in production. The efflux of sugars by bacteria is poorly understood, even in model systems like E. coli, and in this project the student will identify and manipulate efflux proteins that are involved in the export of HMOs. One family of proteins known to be important are the Set efflux systems and the student will seek additional members of this family with improved properties for the process. In parallel, the student will attempt to study the structure & function of the Set proteins in more detail using vesicles, and, if possible, purify and reconstitute proteins, to examine their affinity and turnover rate for HMOs and other di- and oligo-saccharides. The student will gain a broad understanding of the molecular microbiology and biochemistry of transport proteins, in the context of a process with direct relevance to industry, but yet also fundamentally understudied in any bacterial system. While the project is based in labs at York Biology and the student forms part of the White Rose DTP iCASE Bioeconomy cohort, there are also opportunities for the student to work in Copenhagen with the iCASE partner, Glycom, during the project.