Bernhardt, ThomasShih, WilliamDevlin, AbigailWeiss, RonZiesack, Marika2019-05-162018-112018-09-162018http://nrs.harvard.edu/urn-3:HUL.InstRepos:39947209Microbes have been used for production of food and beverages for thousands of years. In the last century we have begun to modify them by means of genetic engineering to produce more complex compounds and we have gained knowledge of how our own microbiome influences our body in health and disease. In my dissertation I contribute together with my colleagues and collaborators to the domestication of microbes for both production of bio-based chemicals and microbiota applications through synthetic biology. In chapter 2 I will discuss our efforts to improve production of fatty acid derived chemicals by protein engineering. We generated chimeric thioesterases with novel functions and gained mechanistic insight into their microbial productivity and chain-length specificity. In chapter 3 I will discuss our work on engineering four gut dwelling bacterial species to cooperate via metabolite cross-feeding. We showed that introducing these positive interactions in synthetic consortia generates bacterial composition that is characterized my evenness and robust towards perturbations in vitro. We further demonstrate that the engineered consortia composition is more even in the animal gut compared to the WT consortia. Lastly, in chapter 4 I will explore the genome of a natural E. coli isolate that is genetically tractable and colonizes the mouse gut well, with the aim to identify characteristics that aid in gut colonization. The field of metabolic engineering branches into two main tasks of improving production of bio-based chemicals and understanding and ultimately modifying the microbiome for health purposes. The work done in this dissertation contributes to both of these branches by applying synthetic biology approaches.application/pdfenBiology, MicrobiologyThesis or Dissertation2019-05-16