Moser, AndréAndréMoserKuchemüller, Kim BeatriceKim BeatriceKuchemüllerDeppe, SaharSaharDeppeHernández Rodríguez, TanjaTanjaHernández RodríguezFrahm, BjörnBjörnFrahmPörtner, RalfRalfPörtnerHass, Volker C.Volker C.HassMöller, JohannesJohannesMöller2021-11-042021-11-042021-01-20Bioprocess and Biosystems Engineering 44 (4): 683-700 (2021-04-01)http://hdl.handle.net/11420/10744Bioprocess development and optimization are still cost- and time-intensive due to the enormous number of experiments involved. In this study, the recently introduced model-assisted Design of Experiments (mDoE) concept (Möller et al. in Bioproc Biosyst Eng 42(5):867, https://doi.org/10.1007/s00449-019-02089-7, 2019) was extended and implemented into a software (“mDoE-toolbox”) to significantly reduce the number of required cultivations. The application of the toolbox is exemplary shown in two case studies with Saccharomyces cerevisiae. In the first case study, a fed-batch process was optimized with respect to the pH value and linearly rising feeding rates of glucose and nitrogen source. Using the mDoE-toolbox, the biomass concentration was increased by 30% compared to previously performed experiments. The second case study was the whole-cell biocatalysis of ethyl acetoacetate (EAA) to (S)-ethyl-3-hydroxybutyrate (E3HB), for which the feeding rates of glucose, nitrogen source, and EAA were optimized. An increase of 80% compared to a previously performed experiment with similar initial conditions was achieved for the E3HB concentration.en1432-079720214683700Springerhttps://creativecommons.org/licenses/by/4.0/BiocatalysisFed-batch strategyModel-assisted design of experimentsMonte Carlo methodsQuality by designBiowissenschaften, BiologieTechnikJournal Article10.15480/882.386410.1007/s00449-020-02478-310.15480/882.386433471162Article