Dynamic metabolomics differentiates between carbon and energy starvation in recombinant Saccharomyces cerevisiae fermenting xylose
(2012) In Biotechnology for Biofuels 5:34.- Abstract
- Background: The concerted effects of changes in gene expression due to changes in the environment are
ultimately reflected in the metabolome. Dynamics of metabolite concentrations under a certain condition can
therefore give a description of the cellular state with a high degree of functional information. We used this
potential to evaluate the metabolic status of two recombinant strains of Saccharomyces cerevisiae during
anaerobic batch fermentation of a glucose/xylose mixture. Two isogenic strains were studied, differing only in
the pathways used for xylose assimilation: the oxidoreductive pathway with xylose reductase (XR) and xylitol
dehydrogenase (XDH) or the isomerization pathway... (More) - Background: The concerted effects of changes in gene expression due to changes in the environment are
ultimately reflected in the metabolome. Dynamics of metabolite concentrations under a certain condition can
therefore give a description of the cellular state with a high degree of functional information. We used this
potential to evaluate the metabolic status of two recombinant strains of Saccharomyces cerevisiae during
anaerobic batch fermentation of a glucose/xylose mixture. Two isogenic strains were studied, differing only in
the pathways used for xylose assimilation: the oxidoreductive pathway with xylose reductase (XR) and xylitol
dehydrogenase (XDH) or the isomerization pathway with xylose isomerase (XI). The isogenic relationship
between the two strains ascertains that the observed responses are a result of the particular xylose pathway
and not due to unknown changes in regulatory systems. An increased understanding of the physiological
state of these strains is important for further development of efficient pentose-utilizing strains for bioethanol
production.
Results: Using LC-MS/MS we determined the dynamics in the concentrations of intracellular metabolites in
central carbon metabolism, nine amino acids, the purine nucleotides and redox cofactors. The general
response to the transition from glucose to xylose was increased concentrations of amino acids and TCA-cycle
intermediates, and decreased concentrations of sugar phosphates and redox cofactors. The two strains
investigated had significantly different uptake rates of xylose which led to an enhanced response in the
XI-strain. Despite the difference in xylose uptake rate, the adenylate energy charge remained high and stable
around 0.8 in both strains. In contrast to the adenylate pool, large changes were observed in the guanylate
pool.
Conclusions: The low uptake of xylose by the XI-strain led to several distinguished responses: depletion of
key metabolites in glycolysis and NADPH, a reduced GTP/GDP ratio and accumulation of PEP and aromatic
amino acids. These changes are strong indicators of carbon starvation. The XR/XDH-strain displayed few such
traits. The coexistence of these traits and a stable adenylate charge indicates that xylose supplies energy to
the cells but does not suppress a response similar to carbon starvation. Particular signals may play a role in
the latter, of which the GTP/GMP ratio could be a candidate as it decreased significantly in both strains. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3127018
- author
- Bergdahl, Basti LU ; Heer, Dominik ; Sauer, Uwe ; Hahn-Hägerdal, Bärbel LU and van Niel, Ed LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Bioethanol, Starvation, Metabolic status, Xylose fermentation, Yeast metabolism, Metabolomics
- in
- Biotechnology for Biofuels
- volume
- 5:34
- publisher
- BioMed Central (BMC)
- external identifiers
-
- wos:000309402800001
- scopus:84860907188
- pmid:22587303
- ISSN
- 1754-6834
- DOI
- 10.1186/1754-6834-5-34
- language
- English
- LU publication?
- yes
- id
- 7381c05d-2849-4a01-b99e-ea6781dfc16b (old id 3127018)
- date added to LUP
- 2016-04-01 13:05:57
- date last changed
- 2022-03-29 05:34:15
@article{7381c05d-2849-4a01-b99e-ea6781dfc16b,
abstract = {{Background: The concerted effects of changes in gene expression due to changes in the environment are<br/><br>
ultimately reflected in the metabolome. Dynamics of metabolite concentrations under a certain condition can<br/><br>
therefore give a description of the cellular state with a high degree of functional information. We used this<br/><br>
potential to evaluate the metabolic status of two recombinant strains of Saccharomyces cerevisiae during<br/><br>
anaerobic batch fermentation of a glucose/xylose mixture. Two isogenic strains were studied, differing only in<br/><br>
the pathways used for xylose assimilation: the oxidoreductive pathway with xylose reductase (XR) and xylitol<br/><br>
dehydrogenase (XDH) or the isomerization pathway with xylose isomerase (XI). The isogenic relationship<br/><br>
between the two strains ascertains that the observed responses are a result of the particular xylose pathway<br/><br>
and not due to unknown changes in regulatory systems. An increased understanding of the physiological<br/><br>
state of these strains is important for further development of efficient pentose-utilizing strains for bioethanol<br/><br>
production.<br/><br>
Results: Using LC-MS/MS we determined the dynamics in the concentrations of intracellular metabolites in<br/><br>
central carbon metabolism, nine amino acids, the purine nucleotides and redox cofactors. The general<br/><br>
response to the transition from glucose to xylose was increased concentrations of amino acids and TCA-cycle<br/><br>
intermediates, and decreased concentrations of sugar phosphates and redox cofactors. The two strains<br/><br>
investigated had significantly different uptake rates of xylose which led to an enhanced response in the<br/><br>
XI-strain. Despite the difference in xylose uptake rate, the adenylate energy charge remained high and stable<br/><br>
around 0.8 in both strains. In contrast to the adenylate pool, large changes were observed in the guanylate<br/><br>
pool.<br/><br>
Conclusions: The low uptake of xylose by the XI-strain led to several distinguished responses: depletion of<br/><br>
key metabolites in glycolysis and NADPH, a reduced GTP/GDP ratio and accumulation of PEP and aromatic<br/><br>
amino acids. These changes are strong indicators of carbon starvation. The XR/XDH-strain displayed few such<br/><br>
traits. The coexistence of these traits and a stable adenylate charge indicates that xylose supplies energy to<br/><br>
the cells but does not suppress a response similar to carbon starvation. Particular signals may play a role in<br/><br>
the latter, of which the GTP/GMP ratio could be a candidate as it decreased significantly in both strains.}},
author = {{Bergdahl, Basti and Heer, Dominik and Sauer, Uwe and Hahn-Hägerdal, Bärbel and van Niel, Ed}},
issn = {{1754-6834}},
keywords = {{Bioethanol; Starvation; Metabolic status; Xylose fermentation; Yeast metabolism; Metabolomics}},
language = {{eng}},
publisher = {{BioMed Central (BMC)}},
series = {{Biotechnology for Biofuels}},
title = {{Dynamic metabolomics differentiates between carbon and energy starvation in recombinant Saccharomyces cerevisiae fermenting xylose}},
url = {{http://dx.doi.org/10.1186/1754-6834-5-34}},
doi = {{10.1186/1754-6834-5-34}},
volume = {{5:34}},
year = {{2012}},
}