Ghadermazi, Parsa, authorChan, Siu Hung, advisorWrighton, Kelly, committee memberReisfeld, Brad, committee member2023-06-012023-06-012023https://hdl.handle.net/10217/236580Zip file contains supplementary files 1 and 2.Gas fermentation provides a promising platform to turn low-cost and readily available single-carbon waste gases into commodity chemicals such as 2,3-butanediol. Clostridium autoethanogenum is usually used as a robust and flexible chassis for gas fermentation. Here, we leveraged on constraints-based stoichiometric modeling and kinetic ensemble modeling of the C. autoethanogenum metabolic network to provide a systematic in silico analysis of metabolic engineering interventions for 2,3-butanediol overproduction and low carbon substrate loss in dissipated CO2. Our analysis allowed us to identify and to assess comparatively the expected performances for a wide range of single, double, and triple interventions. Our analysis managed to individuate bottleneck reactions in relevant metabolic pathways when suggesting intervening strategies. Besides recapitulating intuitive and/or previously attempted genetic modifications, our analysis neatly outlined that the interventions - at least partially - impinging on by-products branching from acetyl-CoA and pyruvate (acetate, ethanol, amino acids) offer valuable alternatives to the interventions focusing directly on the specific branch from pyruvate to 2,3-butanediol.born digitalmasters thesesZIPXLSXengCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.metabolic engineeringC. autoethanogenumText