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
Number of pages17
JournalEngineering in Life Sciences
Publication statusPublished - 2022


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


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