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Monitoring Intracellular Metabolite Dynamics in Saccharomyces cerevisiae 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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Autores principales: Minden, Steven, Aniolek, Maria, Sarkizi Shams Hajian, Christopher, Teleki, Attila, Zerrer, Tobias, Delvigne, Frank, van Gulik, Walter, Deshmukh, Amit, Noorman, Henk, Takors, Ralf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953226/
https://www.ncbi.nlm.nih.gov/pubmed/35323706
http://dx.doi.org/10.3390/metabo12030263
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author Minden, Steven
Aniolek, Maria
Sarkizi Shams Hajian, Christopher
Teleki, Attila
Zerrer, Tobias
Delvigne, Frank
van Gulik, Walter
Deshmukh, Amit
Noorman, Henk
Takors, Ralf
author_facet Minden, Steven
Aniolek, Maria
Sarkizi Shams Hajian, Christopher
Teleki, Attila
Zerrer, Tobias
Delvigne, Frank
van Gulik, Walter
Deshmukh, Amit
Noorman, Henk
Takors, Ralf
author_sort Minden, Steven
collection PubMed
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. A priori 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 Saccharomyces cerevisiae 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(−1) 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.
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spelling pubmed-89532262022-03-26 Monitoring Intracellular Metabolite Dynamics in Saccharomyces cerevisiae during Industrially Relevant Famine Stimuli Minden, Steven Aniolek, Maria Sarkizi Shams Hajian, Christopher Teleki, Attila Zerrer, Tobias Delvigne, Frank van Gulik, Walter Deshmukh, Amit Noorman, Henk Takors, Ralf Metabolites Article 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. A priori 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 Saccharomyces cerevisiae 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(−1) 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. MDPI 2022-03-18 /pmc/articles/PMC8953226/ /pubmed/35323706 http://dx.doi.org/10.3390/metabo12030263 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Minden, Steven
Aniolek, Maria
Sarkizi Shams Hajian, Christopher
Teleki, Attila
Zerrer, Tobias
Delvigne, Frank
van Gulik, Walter
Deshmukh, Amit
Noorman, Henk
Takors, Ralf
Monitoring Intracellular Metabolite Dynamics in Saccharomyces cerevisiae during Industrially Relevant Famine Stimuli
title Monitoring Intracellular Metabolite Dynamics in Saccharomyces cerevisiae during Industrially Relevant Famine Stimuli
title_full Monitoring Intracellular Metabolite Dynamics in Saccharomyces cerevisiae during Industrially Relevant Famine Stimuli
title_fullStr Monitoring Intracellular Metabolite Dynamics in Saccharomyces cerevisiae during Industrially Relevant Famine Stimuli
title_full_unstemmed Monitoring Intracellular Metabolite Dynamics in Saccharomyces cerevisiae during Industrially Relevant Famine Stimuli
title_short Monitoring Intracellular Metabolite Dynamics in Saccharomyces cerevisiae during Industrially Relevant Famine Stimuli
title_sort monitoring intracellular metabolite dynamics in saccharomyces cerevisiae during industrially relevant famine stimuli
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953226/
https://www.ncbi.nlm.nih.gov/pubmed/35323706
http://dx.doi.org/10.3390/metabo12030263
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