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Flux control-based design of furfural-resistance strains of Saccharomyces cerevisiae for lignocellulosic biorefinery

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Abstract

We have previously developed a dynamic flux balance analysis of Saccharomyces cerevisiae for elucidation of genome-wide flux response to furfural perturbation (Unrean and Franzen, Biotechnol J 10(8):1248–1258, 2015). Herein, the dynamic flux distributions were analyzed by flux control analysis to identify target overexpressed genes for improved yeast robustness against furfural. The flux control coefficient (FCC) identified overexpressing isocitrate dehydrogenase (IDH1), a rate-controlling flux for ethanol fermentation, and dicarboxylate carrier (DIC1), a limiting flux for cell growth, as keys of furfural-resistance phenotype. Consistent with the model prediction, strain characterization showed 1.2- and 2.0-fold improvement in ethanol synthesis and furfural detoxification rates, respectively, by IDH1 overexpressed mutant compared to the control. DIC1 overexpressed mutant grew at 1.3-fold faster and reduced furfural at 1.4-fold faster than the control under the furfural challenge. This study hence demonstrated the FCC-based approach as an effective tool for guiding the design of robust yeast strains.

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Acknowledgements

The research work is financially supported by National Center for Genetic Engineering and Biotechnology, Thailand. The author declares no commercial or financial conflict of interest. The author would like to thank Miss Sutamat Khajeeram for all the helps with HPLC analysis.

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  1. National Center for Genetic Engineering and Biotechnology (BIOTEC), 113 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, Pathumthani, 12120, Thailand

    Pornkamol Unrean

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Correspondence to Pornkamol Unrean.

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Unrean, P. Flux control-based design of furfural-resistance strains of Saccharomyces cerevisiae for lignocellulosic biorefinery. Bioprocess Biosyst Eng 40, 611–623 (2017). https://doi.org/10.1007/s00449-016-1725-3

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  • DOI: https://doi.org/10.1007/s00449-016-1725-3

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