Applied Microbiology and Biotechnology

, Volume 102, Issue 10, pp 4589–4600 | Cite as

HAA1 and PRS3 overexpression boosts yeast tolerance towards acetic acid improving xylose or glucose consumption: unravelling the underlying mechanisms

  • Joana T. Cunha
  • Carlos E. Costa
  • Luís Ferraz
  • Aloia Romaní
  • Björn Johansson
  • Isabel Sá-Correia
  • Lucília Domingues
Applied genetics and molecular biotechnology


Acetic acid tolerance and xylose consumption are desirable traits for yeast strains used in industrial biotechnological processes. In this work, overexpression of a weak acid stress transcriptional activator encoded by the gene HAA1 and a phosphoribosyl pyrophosphate synthetase encoded by PRS3 in a recombinant industrial Saccharomyces cerevisiae strain containing a xylose metabolic pathway was evaluated in the presence of acetic acid in xylose- or glucose-containing media. HAA1 or PRS3 overexpression resulted in superior yeast growth and higher sugar consumption capacities in the presence of 4 g/L acetic acid, and a positive synergistic effect resulted from the simultaneous overexpression of both genes. Overexpressing these genes also improved yeast adaptation to a non-detoxified hardwood hydrolysate with a high acetic acid content. Furthermore, the overexpression of HAA1 and/or PRS3 was found to increase the robustness of yeast cell wall when challenged with acetic acid stress, suggesting the involvement of the modulation of the cell wall integrity pathway. This study clearly shows HAA1 and/or, for the first time, PRS3 overexpression to play an important role in the improvement of industrial yeast tolerance towards acetic acid. The results expand the molecular toolbox and add to the current understanding of the mechanisms involved in higher acetic acid tolerance, paving the way for the further development of more efficient industrial processes.


PRS3 and HAA1 overexpression Acetic acid Xylose consumption Industrial Saccharomyces cerevisiae Cell wall robustness 



This study was supported by the Portuguese Foundation for Science and Technology (FCT) by the strategic funding of UID/BIO/04469/2013 unit, MIT-Portugal Program (PhD grant PD/BD/128247/2016 to Joana T. Cunha), COMPETE 2020 (POCI-01-0145-FEDER-006684), BioTecNorte operation (NORTE-01-0145-FEDER-000004) and MultiBiorefinery project (POCI-01-0145-FEDER-016403). Funding received by Institute for Bioengineering and Biosciences (IBB) from FCT (UID/BIO/04565/2013) and from Programa Operacional Regional de Lisboa 2020 (Project No. 007317) is acknowledged. BJ was supported through the strategic program UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

253_2018_8955_MOESM1_ESM.pdf (325 kb)
ESM 1 (PDF 324 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Centre of Biological Engineering (CEB)University of MinhoBragaPortugal
  2. 2.Center of Molecular and Environmental Biology (CBMA)University of MinhoBragaPortugal
  3. 3.Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior TécnicoUniversidade de LisboaLisbonPortugal

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