Influence of oxygen concentration on the metabolism of Penicillium chrysogenum
Abstract 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 produc...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley-VCH
2023-01-01
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| Series: | Engineering in Life Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/elsc.202100139 |
| _version_ | 1797961331931873280 |
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| author | Agnes Janoska Jelle J. Verheijen Wenjung Tang Queenie Lee Baukje Sikkema Walter M. van Gulik |
| author_facet | Agnes Janoska Jelle J. Verheijen Wenjung Tang Queenie Lee Baukje Sikkema Walter M. van Gulik |
| author_sort | Agnes Janoska |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T00:57:01Z |
| format | Article |
| id | doaj.art-d7ccb160d2d54a06b5cb9756b09c5a50 |
| institution | Directory Open Access Journal |
| issn | 1618-0240 1618-2863 |
| language | English |
| last_indexed | 2024-04-11T00:57:01Z |
| publishDate | 2023-01-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Engineering in Life Sciences |
| spelling | doaj.art-d7ccb160d2d54a06b5cb9756b09c5a502023-01-05T02:40:22ZengWiley-VCHEngineering in Life Sciences1618-02401618-28632023-01-01231n/an/a10.1002/elsc.202100139Influence of oxygen concentration on the metabolism of Penicillium chrysogenumAgnes Janoska0Jelle J. Verheijen1Wenjung Tang2Queenie Lee3Baukje Sikkema4Walter M. van Gulik5Department of Biotechnology Delft University of Technology Delft The NetherlandsDepartment of Biotechnology Delft University of Technology Delft The NetherlandsDepartment of Biotechnology Delft University of Technology Delft The NetherlandsDepartment of Biotechnology Delft University of Technology Delft The NetherlandsDepartment of Biotechnology Delft University of Technology Delft The NetherlandsDepartment of Biotechnology Delft University of Technology Delft The NetherlandsAbstract 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.https://doi.org/10.1002/elsc.202100139black box modelmetabolic modelingoxygen limitationpenicillin pathwayscale‐down |
| spellingShingle | Agnes Janoska Jelle J. Verheijen Wenjung Tang Queenie Lee Baukje Sikkema Walter M. van Gulik Influence of oxygen concentration on the metabolism of Penicillium chrysogenum Engineering in Life Sciences black box model metabolic modeling oxygen limitation penicillin pathway scale‐down |
| title | Influence of oxygen concentration on the metabolism of Penicillium chrysogenum |
| title_full | Influence of oxygen concentration on the metabolism of Penicillium chrysogenum |
| title_fullStr | Influence of oxygen concentration on the metabolism of Penicillium chrysogenum |
| title_full_unstemmed | Influence of oxygen concentration on the metabolism of Penicillium chrysogenum |
| title_short | Influence of oxygen concentration on the metabolism of Penicillium chrysogenum |
| title_sort | influence of oxygen concentration on the metabolism of penicillium chrysogenum |
| topic | black box model metabolic modeling oxygen limitation penicillin pathway scale‐down |
| url | https://doi.org/10.1002/elsc.202100139 |
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