Influence of oxygen concentration on the metabolism of Penicillium chrysogenum

Agnes Janoska*, Jelle J. Verheijen, Wenjung Tang, Queenie Lee, Baukje Sikkema, Walter M. van Gulik

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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In large-scale bioreactors, there is often insufficient mixing and as a consequence, cells experience uneven substrate and oxygen levels that influence product formation. In this study, the influence of dissolved oxygen (DO) gradients on the primary and secondary metabolism of a high producing industrial strain of Penicillium chrysogenum was investigated. Within a wide range of DO concentrations, obtained under chemostat conditions, we observed different responses from P. chrysogenum: (i) no influence on growth or penicillin production (>0.025 mmol L−1); (ii) reduced penicillin production, but no growth limitation (0.013–0.025 mmol L−1); and (iii) growth and penicillin production limitations (<0.013 mmol L−1). In addition, scale down experiments were performed by oscillating the DO concentration in the bioreactor. We found that during DO oscillation, the penicillin production rate decreased below the value observed when a constant DO equal to the average oscillating DO value was used. To understand and predict the influence of oxygen levels on primary metabolism and penicillin production, we developed a black box model that was linked to a detailed kinetic model of the penicillin pathway. The model simulations represented the experimental data during the step experiments; however, during the oscillation experiments the predictions deviated, indicating the involvement of the central metabolism in penicillin production.

Original languageEnglish
Article numbere2100139
Number of pages17
JournalEngineering in Life Sciences
Issue number1
Publication statusPublished - 2022


  • black box model
  • metabolic modeling
  • oxygen limitation
  • penicillin pathway
  • scale-down


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