TY  - EJOUR
AU  - Ziegler, Anita L.
AU  - Manchanda, Ashutosh
AU  - Stumm, Marc-Daniel
AU  - Blank, Lars M.
AU  - Mitsos, Alexander
TI  - Simultaneous design of fermentation and microbe
PB  - arXiv
M1  - FZJ-2024-03067
PY  - 2024
AB  - 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.
KW  - Optimization and Control (math.OC) (Other)
KW  - FOS: Mathematics (Other)
LB  - PUB:(DE-HGF)25
DO  - DOI:10.48550/ARXIV.2401.16188
UR  - https://juser.fz-juelich.de/record/1025678
ER  -