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Identification of informative metabolic responses using a minibioreactor: a small step change in the glucose supply rate creates a large metabolic response in Saccharomyces cerevisiae
Author(s) -
Aboka Fredrick O.,
Winden Wouter A.,
Reginald Mashego M.,
Gulik Walter M.,
Berg Marco,
Oudshoorn Arthur,
Heijnen Joseph J.
Publication year - 2012
Publication title -
yeast
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.923
H-Index - 102
eISSN - 1097-0061
pISSN - 0749-503X
DOI - 10.1002/yea.2892
Subject(s) - trehalose , glycogen , biology , saccharomyces cerevisiae , biophysics , glycolysis , biochemistry , bioreactor , carbohydrate metabolism , stimulus (psychology) , carbon dioxide , metabolism , yeast , botany , ecology , psychology , psychotherapist
In this study, a previously developed mini‐bioreactor, the Biocurve, was used to identify an informative stimulus–response experiment. The identified stimulus–response experiment was a modest 50% shift‐up in glucose uptake rate ( q GLC) that unexpectedly resulted in a disproportionate transient metabolic response. The 50% shift‐up in q GLC in the Biocurve resulted in a near tripling of the online measured oxygen uptake ( q O 2 ) and carbon dioxide production ( q CO 2 ) rates, suggesting a considerable mobilization of glycogen and trehalose. The 50% shift‐up in q GLC was subsequently studied in detail in a conventional bioreactor (4 l working volume), which confirmed the results obtained with the Biocurve. Especially relevant is the observation that the 50% increase in glucose uptake rate led to a three‐fold increase in glycolytic flux, due to mobilization of storage materials. This explains the unexpected ethanol and acetate secretion after the shift‐up, in spite of the fact that after the shift‐up the q GLC was far less than the critical value. Moreover, these results show that the correct in vivo fluxes in glucose pulse experiments cannot be obtained from the uptake and secretion rates only. Instead, the storage fluxes must also be accurately quantified. Finally, we speculate on the possible role that the transient increase in dissolved CO 2 immediately after the 50% shift‐up in q GLC could have played a part in triggering glycogen and trehalose mobilization. Copyright © 2012 John Wiley & Sons, Ltd.