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Urban PL Schmidt AM Fagerer SR Amantonico A Ibañez A Jefimovs K Heinemann M Zenobi R 《Molecular bioSystems》2011,7(10):2837-2840
Isotopic labelling of cellular metabolites, used in conjunction with high-density micro-arrays for mass spectrometry enables observation of ATP metabolism in single yeast cells. 相似文献
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Vytautas Galvanauskas Oskars Grigs Juris Vanags Konstantins Dubencovs Valerija Stepanova 《Engineering in Life Science》2013,13(2):172-184
A model‐based approach for optimization and cascade control of dissolved oxygen partial pressure (pO2) and maximization of biomass in fed‐batch cultivations is presented. The procedure is based on the off‐line model‐based optimization of the optimal feeding rate profiles and the subsequent automatic pO2 control using a proposed cascade control technique. During the model‐based optimization of the process, feeding rate profiles are optimized with respect to the imposed technological constraints (initial and maximal cultivation volume, cultivation time, feeding rate range, maximal oxygen transfer rate and pO2 level). The cascade pO2 control is implemented using activation of cascades for agitation, oxygen enrichment, and correction of the preoptimized feeding rate profiles. The proposed approach is investigated in two typical fed‐batch processes with Escherichia coli and Saccharomyces cerevisiae. The obtained results show that it was possible to achieve sufficiently high biomass levels with respect to the given technological constraints and to improve controllability of the investigated processes. 相似文献
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Florian Buettner Kyle Jay Harry Wischnewski Thomas Stadelmann Shady Saad Konstantins Jefimovs Madina Mansurova Juan Gerez Claus M. Azzalin Reinhard Dechant Alfredo J. Ibáñez 《Metabolomics : Official journal of the Metabolomic Society》2017,13(5):53
Introduction
The alternative lengthening of telomeres (ALT) mechanism was first observed in the model organism S. cerevisiae. Interestingly, this mechanism is necessary for the viability of some tumor cells. Unfortunately, its molecular underpinnings are not yet completely understood.Objective
Here, we combine carefully designed non-targeted mass spectrometry-based metabolomics experiments with a bioinformatics approach to characterize the ALT positive phenotype observed in yeast at the metabolomics level.Methods
We profiled the metabolome using mass spectrometry in yeast strains that have lost telomerase expression, as well as that in pre-senescence and the rescued states. To dissect unwanted technical variation from biologically relevant variation between these states, we used a two-step normalization strategy, i.e., first, an empirical Bayesian framework; and next, we corrected for second-order technical effects.Results
Our results show that ALT-positive yeast strains present two different types of metabolic responses to the genetically-induced telomerase dysfunction: (i) systemic and (ii) specific. The key-difference between these responses is that the systemic response lasts even after the yeast strains have been genetically rescued, while the specific response does not. Interestingly, these metabolic changes can be associated with generic stress responses (e.g., DNA damage) as well as specific responses like accelerated aging of early telomerase-inactivation.Conclusions
A mass spectrometry-based metabolomics approach reveals two distinct types of metabolomics response to telomerase dysfunction in yeast. By identifying these changes in protein (e.g., ARG7, and ARG1), and metabolite (e.g., dATP, and dDTP) amounts, we complement the available information on ALT at the genome-wide level.
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