Monitoring Intracellular Metabolite Dynamics in <i>Saccharomyces cerevisiae</i> during Industrially Relevant Famine Stimuli
Carbon limitation is a common feeding strategy in bioprocesses to enable an efficient microbiological conversion of a substrate to a product. However, industrial settings inherently promote mixing insufficiencies, creating zones of famine conditions. Cells frequently traveling through such regions r...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/3/263 |
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| author | Steven Minden Maria Aniolek Christopher Sarkizi Shams Hajian Attila Teleki Tobias Zerrer Frank Delvigne Walter van Gulik Amit Deshmukh Henk Noorman Ralf Takors |
| author_facet | Steven Minden Maria Aniolek Christopher Sarkizi Shams Hajian Attila Teleki Tobias Zerrer Frank Delvigne Walter van Gulik Amit Deshmukh Henk Noorman Ralf Takors |
| author_sort | Steven Minden |
| collection | DOAJ |
| description | Carbon limitation is a common feeding strategy in bioprocesses to enable an efficient microbiological conversion of a substrate to a product. However, industrial settings inherently promote mixing insufficiencies, creating zones of famine conditions. Cells frequently traveling through such regions repeatedly experience substrate shortages and respond individually but often with a deteriorated production performance. <i>A priori</i> knowledge of the expected strain performance would enable targeted strain, process, and bioreactor engineering for minimizing performance loss. Today, computational fluid dynamics (CFD) coupled to data-driven kinetic models are a promising route for the in silico investigation of the impact of the dynamic environment in the large-scale bioreactor on microbial performance. However, profound wet-lab datasets are needed to cover relevant perturbations on realistic time scales. As a pioneering study, we quantified intracellular metabolome dynamics of <i>Saccharomyces cerevisiae</i> following an industrially relevant famine perturbation. Stimulus-response experiments were operated as chemostats with an intermittent feed and high-frequency sampling. Our results reveal that even mild glucose gradients in the range of 100 μmol·L<sup>−1</sup> impose significant perturbations in adapted and non-adapted yeast cells, altering energy and redox homeostasis. Apparently, yeast sacrifices catabolic reduction charges for the sake of anabolic persistence under acute carbon starvation conditions. After repeated exposure to famine conditions, adapted cells show 2.7% increased maintenance demands. |
| first_indexed | 2024-03-09T13:20:32Z |
| format | Article |
| id | doaj.art-865cd1a89e874141b37616a6efcb65f8 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T13:20:32Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-865cd1a89e874141b37616a6efcb65f82023-11-30T21:30:08ZengMDPI AGMetabolites2218-19892022-03-0112326310.3390/metabo12030263Monitoring Intracellular Metabolite Dynamics in <i>Saccharomyces cerevisiae</i> during Industrially Relevant Famine StimuliSteven Minden0Maria Aniolek1Christopher Sarkizi Shams Hajian2Attila Teleki3Tobias Zerrer4Frank Delvigne5Walter van Gulik6Amit Deshmukh7Henk Noorman8Ralf Takors9Institute of Biochemical Engineering, University of Stuttgart, 70569 Stuttgart, GermanyInstitute of Biochemical Engineering, University of Stuttgart, 70569 Stuttgart, GermanyInstitute of Biochemical Engineering, University of Stuttgart, 70569 Stuttgart, GermanyInstitute of Biochemical Engineering, University of Stuttgart, 70569 Stuttgart, GermanyInstitute of Biochemical Engineering, University of Stuttgart, 70569 Stuttgart, GermanyMicrobial Processes and Interactions (MiPI), TERRA Research and Teaching Centre, Gembloux Agro Bio Tech, University of Liege, 5030 Gembloux, BelgiumDepartment of Biotechnology, Delft University of Technology, van der Maasweg 6, 2629 HZ Delft, The NetherlandsRoyal DSM, 2613 AX Delft, The NetherlandsRoyal DSM, 2613 AX Delft, The NetherlandsInstitute of Biochemical Engineering, University of Stuttgart, 70569 Stuttgart, GermanyCarbon limitation is a common feeding strategy in bioprocesses to enable an efficient microbiological conversion of a substrate to a product. However, industrial settings inherently promote mixing insufficiencies, creating zones of famine conditions. Cells frequently traveling through such regions repeatedly experience substrate shortages and respond individually but often with a deteriorated production performance. <i>A priori</i> knowledge of the expected strain performance would enable targeted strain, process, and bioreactor engineering for minimizing performance loss. Today, computational fluid dynamics (CFD) coupled to data-driven kinetic models are a promising route for the in silico investigation of the impact of the dynamic environment in the large-scale bioreactor on microbial performance. However, profound wet-lab datasets are needed to cover relevant perturbations on realistic time scales. As a pioneering study, we quantified intracellular metabolome dynamics of <i>Saccharomyces cerevisiae</i> following an industrially relevant famine perturbation. Stimulus-response experiments were operated as chemostats with an intermittent feed and high-frequency sampling. Our results reveal that even mild glucose gradients in the range of 100 μmol·L<sup>−1</sup> impose significant perturbations in adapted and non-adapted yeast cells, altering energy and redox homeostasis. Apparently, yeast sacrifices catabolic reduction charges for the sake of anabolic persistence under acute carbon starvation conditions. After repeated exposure to famine conditions, adapted cells show 2.7% increased maintenance demands.https://www.mdpi.com/2218-1989/12/3/263scale-upscale-downmetabolomicsbioreactorsystems biologybaker’s yeast |
| spellingShingle | Steven Minden Maria Aniolek Christopher Sarkizi Shams Hajian Attila Teleki Tobias Zerrer Frank Delvigne Walter van Gulik Amit Deshmukh Henk Noorman Ralf Takors Monitoring Intracellular Metabolite Dynamics in <i>Saccharomyces cerevisiae</i> during Industrially Relevant Famine Stimuli Metabolites scale-up scale-down metabolomics bioreactor systems biology baker’s yeast |
| title | Monitoring Intracellular Metabolite Dynamics in <i>Saccharomyces cerevisiae</i> during Industrially Relevant Famine Stimuli |
| title_full | Monitoring Intracellular Metabolite Dynamics in <i>Saccharomyces cerevisiae</i> during Industrially Relevant Famine Stimuli |
| title_fullStr | Monitoring Intracellular Metabolite Dynamics in <i>Saccharomyces cerevisiae</i> during Industrially Relevant Famine Stimuli |
| title_full_unstemmed | Monitoring Intracellular Metabolite Dynamics in <i>Saccharomyces cerevisiae</i> during Industrially Relevant Famine Stimuli |
| title_short | Monitoring Intracellular Metabolite Dynamics in <i>Saccharomyces cerevisiae</i> during Industrially Relevant Famine Stimuli |
| title_sort | monitoring intracellular metabolite dynamics in i saccharomyces cerevisiae i during industrially relevant famine stimuli |
| topic | scale-up scale-down metabolomics bioreactor systems biology baker’s yeast |
| url | https://www.mdpi.com/2218-1989/12/3/263 |
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