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
AU - Pitkänen, Juha-Pekka
AU - Ruohonen, Laura
AU - Jouhten, Paula
PY - 2016/1
Y1 - 2016/1
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 - Metabolic modelling
KW - Saccharomyces cerevisiae
KW - Xylose
KW - Gene expression
KW - Anaerobic
KW - PENTOSE-PHOSPHATE PATHWAY
KW - FLUX BALANCE ANALYSIS
KW - TRANSCRIPTIONAL REGULATION
KW - ETHANOL-PRODUCTION
KW - PICHIA-STIPITIS
KW - XYLITOL-DEHYDROGENASE
KW - SYSTEMS BIOLOGY
KW - FUNCTIONAL EXPRESSION
KW - ESCHERICHIA-COLI
KW - OXIDATIVE STRESS
U2 - 10.1007/s00253-015-7038-7
DO - 10.1007/s00253-015-7038-7
M3 - Article
SN - 0175-7598
VL - 100
SP - 969
EP - 985
JO - Applied Microbiology and Biotechnology
JF - Applied Microbiology and Biotechnology
IS - 2
ER -