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001025678 1001_ $$0P:(DE-HGF)0$$aZiegler, Anita L.$$b0
001025678 245__ $$aSimultaneous design of fermentation and microbe
001025678 260__ $$barXiv$$c2024
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001025678 520__ $$aConstraint-based optimization of microbial strains and model-based bioprocess design have been used extensively to enhance yields in biotechnological processes. However, strain and process optimization are usually carried out in sequential steps, causing underperformance of the biotechnological process when scaling up to industrial fermentation conditions. Herein, we propose the optimization formulation SimulKnock that combines the optimization of a fermentation process with metabolic network design in a bilevel optimization program. The upper level maximizes space-time yield and includes mass balances of a continuous fermentation, while the lower level is based on flux balance analysis. SimulKnock predicts optimal gene deletions and finds the optimal trade-off between growth rate and product yield. Results of a case study with a genome-scale metabolic model of E. coli indicate higher space-time yields than a sequential approach using OptKnock for almost all target products considered. By leveraging SimulKnock, we reduce the gap between strain and process optimization.
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001025678 650_7 $$2Other$$aOptimization and Control (math.OC)
001025678 650_7 $$2Other$$aFOS: Mathematics
001025678 7001_ $$0P:(DE-HGF)0$$aManchanda, Ashutosh$$b1
001025678 7001_ $$0P:(DE-HGF)0$$aStumm, Marc-Daniel$$b2
001025678 7001_ $$0P:(DE-HGF)0$$aBlank, Lars M.$$b3
001025678 7001_ $$0P:(DE-Juel1)172025$$aMitsos, Alexander$$b4$$eCorresponding author$$ufzj
001025678 773__ $$a10.48550/ARXIV.2401.16188
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