[en] 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.
Disciplines :
Biotechnology
Author, co-author :
Minden, Steven ; Institute of Biochemical Engineering, University of Stuttgart, 70569 Stuttgart
Aniolek, Maria; Institute of Biochemical Engineering, University of Stuttgart, 70569 Stuttgart,
Sarkizi Shams Hajian, Christopher ; Institute of Biochemical Engineering, University of Stuttgart, 70569 Stuttgart
Teleki, Attila; Institute of Biochemical Engineering, University of Stuttgart, 70569 Stuttgart,
Zerrer, Tobias; Institute of Biochemical Engineering, University of Stuttgart, 70569 Stuttgart,
Delvigne, Frank ; Université de Liège - ULiège > Département GxABT > Microbial technologies ; Microbial Processes and Interactions (MiPI), TERRA Research and Teaching Centre
van Gulik, Walter; Department of Biotechnology, Delft University of Technology, van der Maasweg 6,
Deshmukh, Amit; Royal DSM, 2613 AX Delft, The Netherlands.
Noorman, Henk; Royal DSM, 2613 AX Delft, The Netherlands. ; Department of Biotechnology, Delft University of Technology, 2628 CD Delft, The
Takors, Ralf; Institute of Biochemical Engineering, University of Stuttgart, 70569 Stuttgart,
Language :
English
Title :
Monitoring Intracellular Metabolite Dynamics in Saccharomyces cerevisiae during Industrially Relevant Famine Stimuli.
Publication date :
18 March 2022
Journal title :
Metabolites
eISSN :
2218-1989
Publisher :
MDPI AG, Basel, Ch
Volume :
12
Issue :
3
Peer reviewed :
Peer Reviewed verified by ORBi
Funding number :
FKZ 031B0629/Federal Ministry of Education and Research/; 722361/ERA CoBioTech/
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