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@ARTICLE{Ziegler:1025678,
      author       = {Ziegler, Anita L. and Manchanda, Ashutosh and Stumm,
                      Marc-Daniel and Blank, Lars M. and Mitsos, Alexander},
      title        = {{S}imultaneous design of fermentation and microbe},
      publisher    = {arXiv},
      reportid     = {FZJ-2024-03067},
      year         = {2024},
      abstract     = {Constraint-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.},
      keywords     = {Optimization and Control (math.OC) (Other) / FOS:
                      Mathematics (Other)},
      cin          = {IEK-10},
      cid          = {I:(DE-Juel1)IEK-10-20170217},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)25},
      doi          = {10.48550/ARXIV.2401.16188},
      url          = {https://juser.fz-juelich.de/record/1025678},
}