Xylose-induced dynamic effects on metabolism and gene expression in engineered Saccharomyces cerevisiae in anaerobic glucose-xylose cultures

Susanne Alff-Tuomala, Laura Salusjärvi, Dorothee Barth, Merja Oja, Merja E. Penttilä, Juha Pekka Pitkänen, Laura Ruohonen, Paula Jouhten

Research output: Contribution to journalArticleScientificpeer-review

19 Citations (Scopus)

Abstract

Xylose is present with glucose in lignocellulosic streams available for valorisation to biochemicals. Saccharomyces cerevisiae has excellent characteristics as a host for the bioconversion, except that it strongly prefers glucose to xylose, and the co-consumption remains a challenge. Further, since xylose is not a natural substrate of S. cerevisiae, the regulatory response it induces in an engineered strain cannot be expected to have evolved for its utilisation. Xylose-induced effects on metabolism and gene expression during anaerobic growth of an engineered strain of S. cerevisiae on medium containing both glucose and xylose medium were quantified. The gene expression of S. cerevisiae with an XR-XDH pathway for xylose utilisation was analysed throughout the cultivation: at early cultivation times when mainly glucose was metabolised, at times when xylose was co-consumed in the presence of low glucose concentrations, and when glucose had been depleted and only xylose was being consumed. Cultivations on glucose as a sole carbon source were used as a control. Genome-scale dynamic flux balance analysis models were simulated to analyse the metabolic dynamics of S. cerevisiae. The simulations quantitatively estimated xylose-dependent flux dynamics and challenged the utilisation of the metabolic network. A relative increase in xylose utilisation was predicted to induce the bi-directionality of glycolytic flux and a redox challenge even at low glucose concentrations. Remarkably, xylose was observed to specifically delay the glucose-dependent repression of particular genes in mixed glucose-xylose cultures compared to glucose cultures. The delay occurred at a cultivation time when the metabolic flux activities were similar in the both cultures.
Original languageEnglish
Pages (from-to)969-985
JournalApplied Microbiology and Biotechnology
Volume100
Issue number2
DOIs
Publication statusPublished - 2016
MoE publication typeA1 Journal article-refereed

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Xylose
Saccharomyces cerevisiae
Gene Expression
Glucose
xylose-glucose
Metabolic Networks and Pathways
Oxidation-Reduction
Carbon
Genome
Growth

Keywords

  • gene expression
  • metabolic modelling
  • saccharomyces cerevisiae
  • xylose

Cite this

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title = "Xylose-induced dynamic effects on metabolism and gene expression in engineered Saccharomyces cerevisiae in anaerobic glucose-xylose cultures",
abstract = "Xylose is present with glucose in lignocellulosic streams available for valorisation to biochemicals. Saccharomyces cerevisiae has excellent characteristics as a host for the bioconversion, except that it strongly prefers glucose to xylose, and the co-consumption remains a challenge. Further, since xylose is not a natural substrate of S. cerevisiae, the regulatory response it induces in an engineered strain cannot be expected to have evolved for its utilisation. Xylose-induced effects on metabolism and gene expression during anaerobic growth of an engineered strain of S. cerevisiae on medium containing both glucose and xylose medium were quantified. The gene expression of S. cerevisiae with an XR-XDH pathway for xylose utilisation was analysed throughout the cultivation: at early cultivation times when mainly glucose was metabolised, at times when xylose was co-consumed in the presence of low glucose concentrations, and when glucose had been depleted and only xylose was being consumed. Cultivations on glucose as a sole carbon source were used as a control. Genome-scale dynamic flux balance analysis models were simulated to analyse the metabolic dynamics of S. cerevisiae. The simulations quantitatively estimated xylose-dependent flux dynamics and challenged the utilisation of the metabolic network. A relative increase in xylose utilisation was predicted to induce the bi-directionality of glycolytic flux and a redox challenge even at low glucose concentrations. Remarkably, xylose was observed to specifically delay the glucose-dependent repression of particular genes in mixed glucose-xylose cultures compared to glucose cultures. The delay occurred at a cultivation time when the metabolic flux activities were similar in the both cultures.",
keywords = "gene expression, metabolic modelling, saccharomyces cerevisiae, xylose",
author = "Susanne Alff-Tuomala and Laura Salusj{\"a}rvi and Dorothee Barth and Merja Oja and Penttil{\"a}, {Merja E.} and Pitk{\"a}nen, {Juha Pekka} and Laura Ruohonen and Paula Jouhten",
year = "2016",
doi = "10.1007/s00253-015-7038-7",
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Xylose-induced dynamic effects on metabolism and gene expression in engineered Saccharomyces cerevisiae in anaerobic glucose-xylose cultures. / Alff-Tuomala, Susanne; Salusjärvi, Laura; Barth, Dorothee; Oja, Merja; Penttilä, Merja E.; Pitkänen, Juha Pekka; Ruohonen, Laura; Jouhten, Paula.

In: Applied Microbiology and Biotechnology, Vol. 100, No. 2, 2016, p. 969-985.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Xylose-induced dynamic effects on metabolism and gene expression in engineered Saccharomyces cerevisiae in anaerobic glucose-xylose cultures

AU - Alff-Tuomala, Susanne

AU - Salusjärvi, Laura

AU - Barth, Dorothee

AU - Oja, Merja

AU - Penttilä, Merja E.

AU - Pitkänen, Juha Pekka

AU - Ruohonen, Laura

AU - Jouhten, Paula

PY - 2016

Y1 - 2016

N2 - Xylose is present with glucose in lignocellulosic streams available for valorisation to biochemicals. Saccharomyces cerevisiae has excellent characteristics as a host for the bioconversion, except that it strongly prefers glucose to xylose, and the co-consumption remains a challenge. Further, since xylose is not a natural substrate of S. cerevisiae, the regulatory response it induces in an engineered strain cannot be expected to have evolved for its utilisation. Xylose-induced effects on metabolism and gene expression during anaerobic growth of an engineered strain of S. cerevisiae on medium containing both glucose and xylose medium were quantified. The gene expression of S. cerevisiae with an XR-XDH pathway for xylose utilisation was analysed throughout the cultivation: at early cultivation times when mainly glucose was metabolised, at times when xylose was co-consumed in the presence of low glucose concentrations, and when glucose had been depleted and only xylose was being consumed. Cultivations on glucose as a sole carbon source were used as a control. Genome-scale dynamic flux balance analysis models were simulated to analyse the metabolic dynamics of S. cerevisiae. The simulations quantitatively estimated xylose-dependent flux dynamics and challenged the utilisation of the metabolic network. A relative increase in xylose utilisation was predicted to induce the bi-directionality of glycolytic flux and a redox challenge even at low glucose concentrations. Remarkably, xylose was observed to specifically delay the glucose-dependent repression of particular genes in mixed glucose-xylose cultures compared to glucose cultures. The delay occurred at a cultivation time when the metabolic flux activities were similar in the both cultures.

AB - Xylose is present with glucose in lignocellulosic streams available for valorisation to biochemicals. Saccharomyces cerevisiae has excellent characteristics as a host for the bioconversion, except that it strongly prefers glucose to xylose, and the co-consumption remains a challenge. Further, since xylose is not a natural substrate of S. cerevisiae, the regulatory response it induces in an engineered strain cannot be expected to have evolved for its utilisation. Xylose-induced effects on metabolism and gene expression during anaerobic growth of an engineered strain of S. cerevisiae on medium containing both glucose and xylose medium were quantified. The gene expression of S. cerevisiae with an XR-XDH pathway for xylose utilisation was analysed throughout the cultivation: at early cultivation times when mainly glucose was metabolised, at times when xylose was co-consumed in the presence of low glucose concentrations, and when glucose had been depleted and only xylose was being consumed. Cultivations on glucose as a sole carbon source were used as a control. Genome-scale dynamic flux balance analysis models were simulated to analyse the metabolic dynamics of S. cerevisiae. The simulations quantitatively estimated xylose-dependent flux dynamics and challenged the utilisation of the metabolic network. A relative increase in xylose utilisation was predicted to induce the bi-directionality of glycolytic flux and a redox challenge even at low glucose concentrations. Remarkably, xylose was observed to specifically delay the glucose-dependent repression of particular genes in mixed glucose-xylose cultures compared to glucose cultures. The delay occurred at a cultivation time when the metabolic flux activities were similar in the both cultures.

KW - gene expression

KW - metabolic modelling

KW - saccharomyces cerevisiae

KW - xylose

U2 - 10.1007/s00253-015-7038-7

DO - 10.1007/s00253-015-7038-7

M3 - Article

VL - 100

SP - 969

EP - 985

JO - Applied Microbiology and Biotechnology

JF - Applied Microbiology and Biotechnology

SN - 0175-7598

IS - 2

ER -