Computational fluid dynamics simulation of an industrial P. chrysogenum fermentation with a coupled 9-pool metabolic model: Towards rational scale-down and design optimization

Cees Haringa, Wenjun Tang, Guan Wang, Amit T. Deshmukh, Wouter A. van Winden, Ju Chu, Walter M. van Gulik, Joseph J. Heijnen, Robert F. Mudde, Henk J. Noorman

Research output: Contribution to journalArticleScientificpeer-review

38 Citations (Scopus)
205 Downloads (Pure)

Abstract

We assess the effect of substrate heterogeneity on the metabolic response of P. chrysogenum in industrial bioreactors via the coupling of a 9-pool metabolic model with Euler-Lagrange CFD simulations. In this work, we outline how this coupled hydrodynamic-metabolic modeling can be utilized in 5 steps. (1) A model response study with a fixed spatial extra-cellular glucose concentration gradient, which reveals a drop in penicillin production rate qp of 18–50% for the simulated reactor, depending on model setup. (2) CFD-based scale-down design, where we design a 1-vessel scale down simulator based on the organism lifelines. (3) Scale-down verification, numerically comparing the model response in the proposed scale-down simulator with large-scale CFD response. (4) Reactor design optimization, reducing the drop in penicillin production by a change of feed location. (5) Long-term fed-batch simulation, where we verify model predictions against experimental data, and discuss population heterogeneity. Overall, these steps present a coupled hydrodynamic-metabolic approach towards bioreactor evaluation, scale-down and optimization.

Original languageEnglish
Pages (from-to)12-24
Number of pages13
JournalChemical Engineering Science
Volume175
DOIs
Publication statusPublished - 2018

Keywords

  • CFD
  • Euler-Langrange
  • Industrial
  • Metabolic model
  • Scale-down

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