A General Process-Based Model for Describing the Metabolic Shift in Microbial Cell Cultures.

Area of Science:

• Biotechnology
• Microbial Physiology
• Systems Biology

Background:

• The metabolic shift between respiration and fermentation in microbes impacts biotechnological applications and high-cell-density cultures.
• Existing models often focus on yeast, necessitating broader applicability for prokaryotes.

Purpose of the Study:

• To develop a general process-based model for prokaryotic species like Escherichia coli and Bacillus subtilis.
• To simulate the metabolic shift regulated by glycolytic intermediates and consider bacterial-specific fermentation by-products and toxic compound inhibition.

Main Methods:

• Utilized a System Dynamics approach, extending a yeast model to prokaryotes.
• Incorporated glycolytic intermediates as a central catabolic hub regulating metabolic pathways.
• Modeled mixed fermentation, secondary by-products, and self-produced toxic compound inhibition.

Main Results:

• Simulations accurately reproduced experimental data for various strains of E. coli and B. subtilis.
• The model successfully described microbial dynamics in both batch and fed-batch reactors.
• Validated the model's ability to represent cell growth and fermentation by-product accumulation.

Conclusions:

• A reductionist System Dynamics approach can create simplified macro-kinetic models for microbial systems.
• The proposed model robustly represents cell growth and by-product dynamics in key biotechnological prokaryotes.
• This generalized model aids in optimizing microbial cell factories for industrial applications.