A 9-pool metabolic structured kinetic model describing days to seconds dynamics of growth and product formation by Penicillium chrysogenum

Wenjun Tang, Amit T. Deshmukh, Cees Haringa, Guan Wang, Walter van Gulik, Wouter van Winden, Matthias Reuss, Joseph J. Heijnen, Jianye Xia, Ju Chu*, Henk J. Noorman

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

24 Citations (Scopus)

Abstract

A powerful approach for the optimization of industrial bioprocesses is to perform detailed simulations integrating large-scale computational fluid dynamics (CFD) and cellular reaction dynamics (CRD). However, complex metabolic kinetic models containing a large number of equations pose formidable challenges in CFD-CRD coupling and computation time afterward. This necessitates to formulate a relatively simple but yet representative model structure. Such a kinetic model should be able to reproduce metabolic responses for short-term (mixing time scale of tens of seconds) and long-term (fed-batch cultivation of hours/days) dynamics in industrial bioprocesses. In this paper, we used Penicillium chrysogenum as a model system and developed a metabolically structured kinetic model for growth and production. By lumping the most important intracellular metabolites in 5 pools and 4 intracellular enzyme pools, linked by 10 reactions, we succeeded in maintaining the model structure relatively simple, while providing informative insight into the state of the organism. The performance of this 9-pool model was validated with a periodic glucose feast–famine cycle experiment at the minute time scale. Comparison of this model and a reported black box model for this strain shows the necessity of employing a structured model under feast–famine conditions. This proposed model provides deeper insight into the in vivo kinetics and, most importantly, can be straightforwardly integrated into a computational fluid dynamic framework for simulating complete fermentation performance and cell population dynamics in large scale and small scale fermentors. Biotechnol. Bioeng. 2017;114: 1733–1743.

Original languageEnglish
Pages (from-to)1733-1743
Number of pages11
JournalBiotechnology and Bioengineering
Volume114
Issue number8
DOIs
Publication statusPublished - 1 Aug 2017

Keywords

  • black box model
  • feast–famine
  • kinetics
  • Penicillium chrysogenum
  • structured model

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