Simulation of penicillin production in fed-batch cultivations using a morphologically structured model

Area of Science:

• Biotechnology and Biochemical Engineering
• Mathematical Modeling
• Fermentation Science

Background:

• Fed-batch cultivation is a key process for producing valuable compounds like penicillin.
• Accurate modeling is essential for optimizing biomass and product formation.
• Understanding substrate consumption and product inhibition is crucial for process control.

Purpose of the Study:

• To develop a mathematical model for predicting biomass, penicillin formation, and substrate consumption in fed-batch cultivations.
• To incorporate morphological compartments and substrate inhibition into the model.
• To validate the model's predictive capabilities using experimental data.

Main Methods:

• Formulation of a mathematical model with three biomass morphological compartments.
• Consideration of glucose and corn steep liquor as substrates.
• Estimation of model parameters using an evolutionary algorithm.
• Validation against experimental data from standard and repeated fed-batch cultivations.

Main Results:

• The model accurately describes biomass trends, penicillin formation, and substrate consumption.
• Penicillin formation was localized to specific compartments and shown to be glucose-inhibited.
• Model predictions showed good agreement with experimental measurements across different fed-batch conditions.

Conclusions:

• The developed mathematical model provides a reliable tool for describing and predicting fed-batch cultivation performance.
• The model's ability to capture substrate inhibition and morphological effects enhances its applicability.
• This work contributes to the optimization of penicillin production through improved fermentation modeling.