001025678 001__ 1025678 001025678 005__ 20240712112900.0 001025678 0247_ $$2doi$$a10.48550/ARXIV.2401.16188 001025678 0247_ $$2datacite_doi$$a10.34734/FZJ-2024-03067 001025678 037__ $$aFZJ-2024-03067 001025678 1001_ $$0P:(DE-HGF)0$$aZiegler, Anita L.$$b0 001025678 245__ $$aSimultaneous design of fermentation and microbe 001025678 260__ $$barXiv$$c2024 001025678 3367_ $$0PUB:(DE-HGF)25$$2PUB:(DE-HGF)$$aPreprint$$bpreprint$$mpreprint$$s1714576571_3667 001025678 3367_ $$2ORCID$$aWORKING_PAPER 001025678 3367_ $$028$$2EndNote$$aElectronic Article 001025678 3367_ $$2DRIVER$$apreprint 001025678 3367_ $$2BibTeX$$aARTICLE 001025678 3367_ $$2DataCite$$aOutput Types/Working Paper 001025678 520__ $$aConstraint-based optimization of microbial strains and model-based bioprocess design have been used extensively to enhance yields in biotechnological processes. However, strain and process optimization are usually carried out in sequential steps, causing underperformance of the biotechnological process when scaling up to industrial fermentation conditions. Herein, we propose the optimization formulation SimulKnock that combines the optimization of a fermentation process with metabolic network design in a bilevel optimization program. The upper level maximizes space-time yield and includes mass balances of a continuous fermentation, while the lower level is based on flux balance analysis. SimulKnock predicts optimal gene deletions and finds the optimal trade-off between growth rate and product yield. Results of a case study with a genome-scale metabolic model of E. coli indicate higher space-time yields than a sequential approach using OptKnock for almost all target products considered. By leveraging SimulKnock, we reduce the gap between strain and process optimization. 001025678 536__ $$0G:(DE-HGF)POF4-899$$a899 - ohne Topic (POF4-899)$$cPOF4-899$$fPOF IV$$x0 001025678 588__ $$aDataset connected to DataCite 001025678 650_7 $$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 001025678 8564_ $$uhttps://juser.fz-juelich.de/record/1025678/files/2401.16188v1.pdf$$yOpenAccess 001025678 8564_ $$uhttps://juser.fz-juelich.de/record/1025678/files/2401.16188v1.gif?subformat=icon$$xicon$$yOpenAccess 001025678 8564_ $$uhttps://juser.fz-juelich.de/record/1025678/files/2401.16188v1.jpg?subformat=icon-1440$$xicon-1440$$yOpenAccess 001025678 8564_ $$uhttps://juser.fz-juelich.de/record/1025678/files/2401.16188v1.jpg?subformat=icon-180$$xicon-180$$yOpenAccess 001025678 8564_ $$uhttps://juser.fz-juelich.de/record/1025678/files/2401.16188v1.jpg?subformat=icon-640$$xicon-640$$yOpenAccess 001025678 909CO $$ooai:juser.fz-juelich.de:1025678$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire 001025678 9101_ $$0I:(DE-588b)36225-6$$6P:(DE-HGF)0$$aRWTH Aachen$$b0$$kRWTH 001025678 9101_ $$0I:(DE-588b)36225-6$$6P:(DE-HGF)0$$aRWTH Aachen$$b1$$kRWTH 001025678 9101_ $$0I:(DE-588b)36225-6$$6P:(DE-HGF)0$$aRWTH Aachen$$b2$$kRWTH 001025678 9101_ $$0I:(DE-588b)36225-6$$6P:(DE-HGF)0$$aRWTH Aachen$$b3$$kRWTH 001025678 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)172025$$aForschungszentrum Jülich$$b4$$kFZJ 001025678 9101_ $$0I:(DE-588b)36225-6$$6P:(DE-Juel1)172025$$aRWTH Aachen$$b4$$kRWTH 001025678 9131_ $$0G:(DE-HGF)POF4-899$$1G:(DE-HGF)POF4-890$$2G:(DE-HGF)POF4-800$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bProgrammungebundene Forschung$$lohne Programm$$vohne Topic$$x0 001025678 9141_ $$y2024 001025678 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 001025678 920__ $$lyes 001025678 9201_ $$0I:(DE-Juel1)IEK-10-20170217$$kIEK-10$$lModellierung von Energiesystemen$$x0 001025678 9801_ $$aFullTexts 001025678 980__ $$apreprint 001025678 980__ $$aVDB 001025678 980__ $$aUNRESTRICTED 001025678 980__ $$aI:(DE-Juel1)IEK-10-20170217 001025678 981__ $$aI:(DE-Juel1)ICE-1-20170217