Model-based process design for surfactin production with Bacillus subtilis

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Pubblicato in:AMB Express vol. 15, no. 1 (Dec 2025), p. 179
Autore principale: Hiller, Eric
Altri autori: Off, Manuel, Dittmann, Holger, Perino, Elvio Henrique Benatto, Lilge, Lars, Hausmann, Rudolf
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Springer Nature B.V.
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100 1 |a Hiller, Eric  |u University of Hohenheim, Department of Bioprocess Engineering, Institute of Food Science and Biotechnology, Stuttgart, Germany (GRID:grid.9464.f) (ISNI:0000 0001 2290 1502) 
245 1 |a Model-based process design for surfactin production with <i>Bacillus subtilis</i> 
260 |b Springer Nature B.V.  |c Dec 2025 
513 |a Journal Article 
520 3 |a Bacillus subtilis is one of the most important production organisms in industrial biotechnology. However, there is still limited knowledge about the kinetics of fed-batch processes in bioreactors, as well as a lack of biological performance indicators, such as production yields, particularly regarding their variation over time. Understanding these kinetics and changes is crucial for optimizing the productivity in fed-batch processes. Fed-batch bioreactor cultures of Bacillus subtilis BMV9 in high cell density processes for surfactin production have been characterized with a kinetic model composed of first-order ordinary differential equations, describing the time course of biomass, substrate, surfactin and acetate. This model contributes to understanding critical restrictions and the knowledge gained was used to design and implement a model-based process. The model integrates biomass growth based on Monod kinetics, substrate consumption, surfactin synthesis and formation of the by-product acetate. After the model was parameterized for B. subtilis BMV9 using 12 different fed-batch bioreactor experiments, the kinetic model was able to accurately describe biomass accumulation, substrate consumption, product formation rates and, to some extent, the overflow metabolism involving acetate. Based on this, the kinetic model was used for a process design, in which the batch was omitted, which led to a product titre of 46.33&#xa0;g/L and a space–time-yield of 2.11&#xa0;g/(L*h) was achieved. The kinetic model developed in this study enables the description of the time course of biomass growth, substrate consumption and product formation and thus significantly improves process understanding. The computation of process parameters, which are not analytically accessible at any time, could be realized. A sensitivity analysis identified the maximum specific growth rate, substrate-related maintenance and the maximum acetate formation rate as key parameters influencing model outputs. 
651 4 |a Germany 
653 |a Monod kinetics 
653 |a Surfactants 
653 |a Surfactin 
653 |a Cell density 
653 |a Sensitivity analysis 
653 |a Biomass 
653 |a Biotechnology 
653 |a Fed batch 
653 |a Batch culture 
653 |a Metabolism 
653 |a Peptides 
653 |a Consumption 
653 |a Batch processing 
653 |a Batch processes 
653 |a Bioreactors 
653 |a Glucose 
653 |a Kinetics 
653 |a Acetic acid 
653 |a Differential equations 
653 |a Enhanced oil recovery 
653 |a Metabolites 
653 |a Ordinary differential equations 
653 |a Process parameters 
653 |a Crude oil 
653 |a Bacillus subtilis 
700 1 |a Off, Manuel  |u University of Hohenheim, Department of Bioprocess Engineering, Institute of Food Science and Biotechnology, Stuttgart, Germany (GRID:grid.9464.f) (ISNI:0000 0001 2290 1502) 
700 1 |a Dittmann, Holger  |u University of Hohenheim, Department of Bioprocess Engineering, Institute of Food Science and Biotechnology, Stuttgart, Germany (GRID:grid.9464.f) (ISNI:0000 0001 2290 1502) 
700 1 |a Perino, Elvio Henrique Benatto  |u University of Hohenheim, Department of Bioprocess Engineering, Institute of Food Science and Biotechnology, Stuttgart, Germany (GRID:grid.9464.f) (ISNI:0000 0001 2290 1502) 
700 1 |a Lilge, Lars  |u University of Hohenheim, Department of Bioprocess Engineering, Institute of Food Science and Biotechnology, Stuttgart, Germany (GRID:grid.9464.f) (ISNI:0000 0001 2290 1502) 
700 1 |a Hausmann, Rudolf  |u University of Hohenheim, Department of Bioprocess Engineering, Institute of Food Science and Biotechnology, Stuttgart, Germany (GRID:grid.9464.f) (ISNI:0000 0001 2290 1502) 
773 0 |t AMB Express  |g vol. 15, no. 1 (Dec 2025), p. 179 
786 0 |d ProQuest  |t Engineering Database 
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