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A Systematic Petri Net Approach for Multiple-Scale Modeling and Simulation of Biochemical Processes

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Abstract

A method to exploit hybrid Petri nets for modeling and simulating biochemical processes in a systematic way was introduced. Both molecular biology and biochemical engineering aspects are manipulated. With discrete and continuous elements, the hybrid Petri nets can easily handle biochemical factors such as metabolites concentration and kinetic behaviors. It is possible to translate both molecular biological behavior and biochemical processes workflow into hybrid Petri nets in a natural manner. As an example, penicillin production bioprocess is modeled to illustrate the concepts of the methodology. Results of the dynamic of production parameters in the bioprocess were simulated and observed diagrammatically. Current problems and post-genomic perspectives were also discussed.

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Abbreviations

F in :

Combined inlet flow rate of all additions (dm3 h−1)

F out :

Outlet flow rate of evaporated water (dm3 h−1)

G :

Glucose concentration (g dm−3)

G in :

Glucose concentration in the feed (g dm−3)

K d :

Autolysis rate constant (h−1)

K h :

Penicillin hydrolysis rate constant (h−1)

K p :

Product saturation constant (g dm−3)

K s :

Substrate saturation constant (g dm−3)

K x :

Growth saturation constant (g g-DW−1)

N :

Soluble organic nitrogen concentration (g dm−3)

P :

Penicillin concentration (as potassium salt) (g-PenGK dm−3)

S :

Substrate concentration (g dm−3)

t :

Time (h)

V :

Culture broth volume (dm3)

X :

Biomass concentration (g-DW dm−3)

Y x/s :

Substrate to biomass yield (g-DW g−1)

Y p/s :

Substrate to penicillin yield (g-PenGK g−1)

ξ :

Specific substrate consumption rate for maintenance (g g-DW−1 h−1)

ξ max :

Maximum specific substrate consumption rate for maintenance (g g-DW−1 h−1)

μ :

Specific biomass growth rate (h−1)

μ max :

Maximum specific biomass growth rate (h−1)

π :

Specific penicillin production rate (g g-DW−1 h−1)

π max :

Maximum specific penicillin production rate (g g-DW−1 h−1)

σ :

Specific substrate consumption rate (g g-DW−1 h−1)

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Acknowledgements

This work was originally prepared in 2001 and renewed recently. Authors are grateful for the support from the International S&T Cooperation Program of China (2009DFA32030), the BMBF International Cooperation Program, Germany (CHN 08/001), and the Program for New Century Excellent Talents in University of China (NCET-07-0740).

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Authors and Affiliations

  1. Department of Bioinformatics, College of Life Sciences, Zhejiang University, Hangzhou, 310058, China

    Ming Chen & Minjie Hu

  2. Department of Bioinformatics and Medical Informatics, Faculty of Technology, University of Bielefeld, 33615, Bielefeld, Germany

    Ralf Hofestädt

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  1. Ming Chen
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  3. Ralf Hofestädt
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Correspondence to Ming Chen.

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Chen, M., Hu, M. & Hofestädt, R. A Systematic Petri Net Approach for Multiple-Scale Modeling and Simulation of Biochemical Processes. Appl Biochem Biotechnol 164, 338–352 (2011). https://doi.org/10.1007/s12010-010-9138-2

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