Monitoring Intracellular Metabolite Dynamics in Saccharomyces cerevisiae during Industrially Relevant Famine Stimuli

Monitoring Intracellular Metabolite Dynamics in Saccharomyces cerevisiae during Industrially Relevant Famine Stimuli

Minden, Steven (University of Stuttgart)
Aniolek, Maria (University of Stuttgart)
Sarkizi Shams Hajian, Christopher (University of Stuttgart)
Teleki, Attila (University of Stuttgart)
Zerrer, Tobias (University of Stuttgart)
Delvigne, Frank (Université de Liège)
van Gulik, W.M. (TU Delft BT/Industriele Microbiologie)
Deshmukh, Amit (DSM)
Noorman, H.J. (TU Delft BT/Bioprocess Engineering; DSM)
Takors, Ralf (University of Stuttgart)

2022

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.

baker’s yeast
bioprocess engineering
bioreactor
chemostat
metabolomics
Saccharomyces cerevisiae
scale-down
scale-up
stimulus-response experiment
substrate gradient
systems biology

http://resolver.tudelft.nl/uuid:50fc8792-d93a-4a2a-8b0a-2c65b51ed64f

https://doi.org/10.3390/metabo12030263

2218-1989

Metabolites, 12 (3)

Institutional Repository

journal article

© 2022 Steven Minden, Maria Aniolek, Christopher Sarkizi Shams Hajian, Attila Teleki, Tobias Zerrer, Frank Delvigne, W.M. van Gulik, Amit Deshmukh, H.J. Noorman, Ralf Takors