Applied Biochemistry and Biotechnology

, Volume 161, Issue 1–8, pp 106–115

Identification of Saccharomyces cerevisiae Genes Involved in the Resistance to Phenolic Fermentation Inhibitors

  • Linda Sundström
  • Simona Larsson
  • Leif J. Jönsson


Saccharomyces cerevisiae was exposed to inhibitory concentrations of the three phenolic phenylpropanoids: coniferyl aldehyde, ferulic acid, and isoeugenol. Deoxyribonucleic acid microarray analysis was employed as one approach to generate a set of candidate genes for deletion mutant analysis to determine the potential contribution of the corresponding gene products to the resistance against toxic concentrations of phenolic fermentation inhibitors. Three S. cerevisiae deletion mutants with increased sensitivity to coniferyl aldehyde were identified: yap1Δ, atr1Δ, and flr1Δ. The rate of reduction of coniferyl aldehyde to coniferyl alcohol decreased sixfold when the gene encoding the transcriptional activator Yap1p was deleted, and threefold when the Yap1p-controlled genes encoding Atr1p and Flr1p were deleted. Growth, glucose consumption, and ethanol formation progressed after a lag phase during which coniferyl aldehyde reduction and coniferyl alcohol formation occurred. The results link ATR1, FLR1, and YAP1 by their ability to confer resistance to coniferyl aldehyde and show that deletion of any of these three genes impairs the ability of S. cerevisiae to withstand coniferyl aldehyde and detoxify it by reduction. Furthermore, the results suggest that overexpression of ATR1, FLR1, and YAP1 is of interest for the construction of novel yeast strains with improved resistance against inhibitors in lignocellulose hydrolysates.


Liquid biofuel Cellulosic ethanol Fermentation inhibitors Saccharomyces cerevisiae Hyperresistance 


  1. 1.
    Borneman, A. R., Chambers, P. J., & Pretorius, I. S. (2007). Trends in Biotechnology, 25, 349–355.CrossRefGoogle Scholar
  2. 2.
    Larsson, S., Quintana-Sáinz, A., Reimann, A., Nilvebrant, N.-O., & Jönsson, L. J. (2000). Applied Biochemistry and Biotechnology, 84–86, 617–632.CrossRefGoogle Scholar
  3. 3.
    Ralph, J., Lundquist, K., Brunow, G., Lu, F., Kim, H., Schatz, P. F., et al. (2004). Phytochemistry Reviews, 3, 29–60.CrossRefGoogle Scholar
  4. 4.
    Ragauskas, A. J., Williams, C. K., Davison, B. H., et al. (2006). Science, 311, 484–489.CrossRefGoogle Scholar
  5. 5.
    Lynd, L. R., Laser, M. S., Bransby, D., Dale, B. E., Davison, B., Hamilton, R., et al. (2008). Nature Biotechnology, 26, 169–172.CrossRefGoogle Scholar
  6. 6.
    Wyman, C. E. (2007). Trends in Biotechnology, 25, 153–157.CrossRefGoogle Scholar
  7. 7.
    Galbe, M., & Zacchi, G. (2007). Advances in Biochemical Engineering, Biotechnology, 108, 41–65.Google Scholar
  8. 8.
    Ando, S., Arai, I., Kiyoto, K., & Hanai, S. (1986). Journal of Fermentation Technology, 64, 567–570.CrossRefGoogle Scholar
  9. 9.
    Jönsson, L. J., Palmqvist, E., Nilvebrant, N.-O., & Hahn-Hägerdal, B. (1998). Applied Microbiology and Biotechnology, 49, 691–697.CrossRefGoogle Scholar
  10. 10.
    Larsson, S., Reimann, A., Nilvebrant, N.-O., & Jönsson, L. J. (1999). Applied Biochemistry and Biotechnology, 77–79, 91–103.CrossRefGoogle Scholar
  11. 11.
    Martín, C., Galbe, M., Wahlbom, C. F., Hahn-Hägerdal, B., & Jönsson, L. J. (2002). Enzyme and Microbial Technology, 31, 274–282.CrossRefGoogle Scholar
  12. 12.
    Larsson, S., Cassland, P., & Jönsson, L. J. (2001). Applied and Environmental Microbiology, 67, 1163–1170.CrossRefGoogle Scholar
  13. 13.
    Larsson, S., Nilvebrant, N.-O., & Jönsson, L. J. (2001). Applied Microbiology and Biotechnology, 57, 167–174.Google Scholar
  14. 14.
    Sherman, F. (1991). Methods in Enzymology, 194, 3–21.CrossRefGoogle Scholar
  15. 15.
    Verduyn, C., Postma, E., Scheffers, W. A., & van Dijken, J. P. (1992). Yeast, 8, 501–517.CrossRefGoogle Scholar
  16. 16.
    Schmitt, M. E., Brown, T. A., & Trumpower, B. L. (1990). Nucleic Acids Research, 18, 3091–3092.CrossRefGoogle Scholar
  17. 17.
    Larsson, S., Palmqvist, E., Hahn-Hägerdal, B., Tengborg, C., Stenberg, K., Zacchi, G., et al. (1999). Enzyme and Microbial Technology, 24, 151–159.CrossRefGoogle Scholar
  18. 18.
    Lee, J., Godon, C., Lagniel, G., Spector, D., Garin, J., Labarre, J., et al. (1999). Journal of Biological Chemistry, 274, 16040–16046.CrossRefGoogle Scholar
  19. 19.
    Rodrigues-Pousada, C. A., Nevitt, T., Menezes, R., Azevedo, D., Pereira, J., & Amaral, C. (2004). FEBS Letters, 567, 80–85.CrossRefGoogle Scholar
  20. 20.
    DeRisi, J. L., Iyer, V. R., & Brown, P. O. (1997). Science, 278, 680–686.CrossRefGoogle Scholar
  21. 21.
    André, B. (1995). Yeast, 11, 1575–1611.CrossRefGoogle Scholar
  22. 22.
    Coleman, S. T., Tseng, E., & Moye-Rowley, W. S. (1997). Journal of Biological Chemistry, 272, 23224–23230.CrossRefGoogle Scholar
  23. 23.
    Nguyen, D.-T., Alarco, A.-M., & Raymond, M. (2001). Journal of Biological Chemistry, 276, 1138–1145.CrossRefGoogle Scholar
  24. 24.
    Sá-Correira, I., dos Santos, S. C., Teixeira, M. C., Cabrito, T. R., & Mira, N. P. (2009). Trends in Microbiology, 17, 22–31.CrossRefGoogle Scholar
  25. 25.
    Viau, C., Pungartnik, C., Schmitt, M. C., Basso, T. S., Henriques, J. A., & Brendel, M. (2006). BioMetals, 19, 705–714.CrossRefGoogle Scholar
  26. 26.
    Tenreiro, S., Fernandes, A. R., & Sá-Correia, I. (2001). Biochemical and Biophysical Research Communications, 280, 216–222.CrossRefGoogle Scholar
  27. 27.
    Brôco, N., Tenreiro, S., Viegas, C. A., & Sá-Correia, I. (1999). Yeast, 15, 1595–1608.CrossRefGoogle Scholar
  28. 28.
    Teixeira, M. C., Dias, P. J., Simões, T., & Sá-Correira, I. (2008). Biochemical and Biophysical Research Communications, 367, 249–255.CrossRefGoogle Scholar
  29. 29.
    Le Crom, S., Devaux, F., Marc, P., Zhang, X., Moye-Rowley, W. S., & Jacq, C. (2002). Molecular and Cellular Biology, 22, 2642–2649.CrossRefGoogle Scholar
  30. 30.
    Jungwirth, H., Wendler, F., Platzer, B., Bergler, H., & Högenauer, G. (2000). European Journal of Biochemistry, 267, 4809–4816.CrossRefGoogle Scholar
  31. 31.
    Kanazawa, S., Driscoll, M., & Struhl, K. (1988). Molecular and Cellular Biology, 8, 664–673.Google Scholar
  32. 32.
    Oskouian, B., & Saba, J. D. (1999). Molecular and General Genetics, 261, 346–353.CrossRefGoogle Scholar
  33. 33.
    Mewes, H. W., Frishman, D., Gruber, C., Geier, B., Haase, D., Kaps, A., et al. (2000). Nucleic Acids Research, 28, 37–40.CrossRefGoogle Scholar

Copyright information

© Humana Press 2009

Authors and Affiliations

  • Linda Sundström
    • 1
    • 2
  • Simona Larsson
    • 3
  • Leif J. Jönsson
    • 4
  1. 1.Applied MicrobiologyLund UniversityLundSweden
  2. 2.AstraZeneca R&D MölndalMölndalSweden
  3. 3.Faculty of Civil EngineeringRiga Technical UniversityRigaLatvia
  4. 4.Department of ChemistryUmeå UniversityUmeåSweden

Personalised recommendations