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Cybernetic modeling based on pathway analysis for Penicillium chrysogenum fed-batch fermentation.

Jun Geng1, Jingqi Yuan

  • 1Department of Automation, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240, Shanghai, People's Republic of China. jungeng@sjtu.edu.cn

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Summary

A new cybernetic model accurately describes Penicillium chrysogenum growth and penicillin production. This macrokinetic model, validated with industrial data, enhances understanding of bioreactor dynamics for improved fermentation processes.

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Area of Science:

  • Biotechnology
  • Biochemical Engineering
  • Systems Biology

Background:

  • Understanding microbial growth and product formation is crucial for optimizing fermentation processes.
  • Penicillium chrysogenum is a key organism for industrial penicillin production.
  • Existing models may not fully capture the complex dynamics of mycelium growth and secondary metabolite synthesis.

Purpose of the Study:

  • To develop a macrokinetic model using cybernetic methodology for mycelium growth and penicillin production.
  • To integrate metabolic flux analysis and cybernetic modeling for Penicillium chrysogenum.
  • To link the model's reaction rates with key bioreactor state variables.

Main Methods:

  • Utilized a cybernetic modeling framework and metabolic flux analysis based on the complete metabolic network of Penicillium chrysogenum.
  • Developed an abstracted cybernetic model to describe substrate consumption, intermediate assimilation, biomass growth, and penicillin formation rates.
  • Integrated the cybernetic model with a bioreactor model to link reaction rates with state variables (mycelium, substrate, product concentrations).
  • Employed the Simplex method for sensitive parameter estimation.
  • Validated the model using data from 20 industrial-scale penicillin cultivation batches.

Main Results:

  • The cybernetic model successfully describes the transient behavior of substrate consumption, biomass growth, and penicillin production.
  • Parameter estimation using the Simplex method identified sensitive model parameters.
  • Model validation with 20 industrial batches demonstrated its predictive capability for penicillin cultivation.

Conclusions:

  • The proposed macrokinetic cybernetic model provides a robust framework for describing Penicillium chrysogenum fermentation.
  • The model enhances the understanding of the interplay between microbial metabolism, growth, and product formation in bioreactors.
  • This approach offers potential for optimizing industrial penicillin production through improved process modeling and control.