Applied Microbiology and Biotechnology

, Volume 86, Issue 6, pp 1915–1924 | Cite as

Transcriptome shifts in response to furfural and acetic acid in Saccharomyces cerevisiae

Genomics, Transcriptomics, Proteomics


Furfural and acetic acid are two prevalent inhibitors to microorganisms during cellulosic ethanol production, but molecular mechanisms of tolerance to these inhibitors are still unclear. In this study, genome-wide transcriptional responses to furfural and acetic acid were investigated in Saccharomyces cerevisiae using microarray analysis. We found that 103 and 227 genes were differentially expressed in the response to furfural and acetic acid, respectively. Furfural downregulated genes related to transcriptional control and translational control, while it upregulated stress-responsive genes. Furthermore, furfural also interrupted the transcription of genes involved in metabolism of essential chemicals, such as etrahydrofolate, spermidine, spermine, and riboflavin monophosphate. Acetic acid downregulated genes encoding mitochondrial ribosomal proteins and genes involved in carbohydrate metabolism and regulation and upregulated genes related to amino acid metabolism. The results revealed that furfural and acetic acid had effects on multiple aspects of cellular metabolism on the transcriptional level and that mitochondria might play important roles in response to both furfural and acetic acid. This research has provided insights into molecular response to furfural and acetic acid in S. cerevisiae, and it will be helpful to construct more resistant strains for cellulosic ethanol production.


Furfural Acetic acid Lignocellulose Bioethanol Microarray 



The authors are grateful for the financial support from the National Natural Science Foundation of China (Key Program Grant No. 20736006), the National Basic Research Program of China (“973” Program: 2007CB714301), Key Projects in the National Science and Technology Pillar Program (No.2007BAD42B02), and the International collaboration project of the Ministry of Science and Technology of the People’s Republic of China (2006DFA62400).

Supplementary material

253_2010_2518_MOESM1_ESM.doc (48 kb)
Table S1 Differentially expressed genes in response to furfural and acetic acid (DOC 47 kb)
253_2010_2518_MOESM2_ESM.doc (48 kb)
Table S2 Downregulated genes involved in transcriptional control and RNA processing in response to furfural addition (DOC 48 kb)
253_2010_2518_MOESM3_ESM.doc (38 kb)
Table S3 Downregulated genes involved in regulation of C-compound and carbohydrate metabolism in response to acetic acid (DOC 38 kb)


  1. Almeida B, Ohlmeier S, Almeida AJ, Madeo F, Leão C, Rodrigues F, Ludovico P (2009) Yeast protein expression profile during acetic acid-induced apoptosis indicates causal involvement of the TOR pathway. Proteomics 9:720–732CrossRefGoogle Scholar
  2. Alvarez-Ordóñez A, Fernández A, Bernardo A, López M (2010) Arginine and lysine decarboxylases and the acid tolerance response of Salmonella Typhimurium. Int J Food Microbiol 136:278–282CrossRefGoogle Scholar
  3. Bauer BE, Rossington D, Mollapour M, Mamnun Y, Kuchler K, Piper PW (2003) Weak organic acid stress inhibits aromatic amino acid uptake by yeast, causing a strong influence of amino acid auxotrophies on the phenotypes of membrane transporter mutants. Eur J Biochem 270:3189–3195CrossRefGoogle Scholar
  4. Blakley RL, Benkovic SJ (1984) Chemistry and biochemistry of folates. John Wiley and Sons, New YorkGoogle Scholar
  5. Cheng JS, Zhou X, Ding MZ, Yuan YJ (2009) Proteomic insights into adaptive responses of Saccharomyces cerevisiae to the repeated vacuum fermentation. Appl Microbiol Biotechnol 83:909–923CrossRefGoogle Scholar
  6. Coburn RF (2009) Polyamine effects on cell function: possible central role of plasma membrane PI(4, 5)P2. J Cell Physiol 221:544–551CrossRefGoogle Scholar
  7. Daran-Lapujade P, Jansen ML, Daran JM, van Gulik W, de Winde JH, Pronk JT (2004) Role of transcriptional regulation in controlling fluxes in central carbon metabolism of Saccharomyces cerevisiae. A chemostat culture study. J Biol Chem 279:9125–9138CrossRefGoogle Scholar
  8. Ding MZ, Tian HC, Cheng JS, Yuan YJ (2009) Inoculum size-dependent interactive regulation of metabolism and stress response of Saccharomyces cerevisiae revealed by comparative metabolomics. J Biotechnol 144:279–286CrossRefGoogle Scholar
  9. Fleck CB, Brock M (2009) Re-characterisation of Saccharomyces cerevisiae Ach1p: fungal CoA-transferases are involved in acetic acid detoxification. Fungal Genet Biol 46:473–485CrossRefGoogle Scholar
  10. Gorsich SW, Dien BS, Nichols NN, Slininger PJ, Liu ZL, Skory CD (2006) Tolerance to furfural-induced stress is associated with pentose phosphate pathway genes ZWF1, GND1, RPE1, and TKL1 in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 71:339–349CrossRefGoogle Scholar
  11. Han PP, Yuan YJ (2009) Lipidomic analysis reveals activation of phospholipid signaling in mechanotransduction of Taxus cuspidata cells in response to shear stress. FASEB J 23:623–630CrossRefGoogle Scholar
  12. Li BZ, Cheng JS, Qiao B, Yuan YJ (2010) Genome-wide transcriptional analysis of Saccharomyces cerevisiae during industrial bioethanol fermentation. J Ind Microbiol Biotechnol 37:43–55CrossRefGoogle Scholar
  13. Lin FM, Qiao B, Yuan YJ (2009a) Comparative proteomic analysis of tolerance and adaptation of ethanologenic Saccharomyces cerevisiae to furfural, a lignocellulosic inhibitory compound. Appl Environ Microbiol 75:3765–3776CrossRefGoogle Scholar
  14. Lin FM, Tan Y, Yuan YJ (2009b) Temporal quantitative proteomics of Saccharomyces cerevisiae in response to a nonlethal concentration of furfural. Proteomics 9:5471–5483CrossRefGoogle Scholar
  15. Liu ZL, Moon J (2009) A novel NADPH-dependent aldehyde reductase gene from Saccharomyces cerevisiae NRRL Y-12632 involved in the detoxification of aldehyde inhibitors derived from lignocellulosic biomass conversion. Gene 446:1–10CrossRefGoogle Scholar
  16. Liu ZL, Moon J, Andersh BJ, Slininger PJ, Weber S (2008) Multiple gene-mediated NAD(P)H-dependent aldehyde reduction is a mechanism of in situ detoxification of furfural and 5-hydroxymethylfurfural by Saccharomyces cerevisiae. Appl Microbiol Biotechnol 81:743–753CrossRefGoogle Scholar
  17. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Methods 25:402–408CrossRefGoogle Scholar
  18. McBride HM, Neuspiel M, Wasiak S (2006) Mitochondria: more than just a powerhouse. Curr Biol 16:R551–R560CrossRefGoogle Scholar
  19. Mollapour M, Shepherd A, Piper PW (2008) Novel stress responses facilitate Saccharomyces cerevisiae growth in the presence of the monocarboxylate preservatives. Yeast 25:169–177CrossRefGoogle Scholar
  20. Mols M, van Kranenburg R, Tempelaars MH, van Schaik W, Moezelaar R, Abee T (2010) Comparative analysis of transcriptional and physiological responses of Bacillus cereus to organic and inorganic acid shocks. Int J Food Microbiol 137:13–21CrossRefGoogle Scholar
  21. Narendranath NV, Thomas KC, Ingledew WM (2001) Effects of acetic acid and lactic acid on the growth of Saccharomyces cerevisiae in a minimal medium. J Ind Microbiol Biotechnol 26:171–177CrossRefGoogle Scholar
  22. Nilsson A, Gorwa-Grauslund MF, Hahn-Hägerdal B, Lidén G (2005) Cofactor dependence in furan reduction by Saccharomyces cerevisiae in fermentation of acid-hydrolyzed lignocellulose. Appl Environ Microbiol 71:7866–7871CrossRefGoogle Scholar
  23. Palmqvist E, Hahn-Hagerdal B (2000) Fermentation of lignocellulosic hydrolysates. II: inhibitors and mechanisms of inhibition. Bioresour Technol 74:25–33CrossRefGoogle Scholar
  24. Palmqvist E, Almeida JS, Hahn-Hägerdal B (1999) Influence of furfural on anaerobic glycolytic kinetics of Saccharomyces cerevisiae in batch culture. Biotechnol Bioeng 62:447–454CrossRefGoogle Scholar
  25. Riego L, Avendaño A, DeLuna A, Rodríguez E, González A (2002) GDH1 expression is regulated by GLN3, GCN4, and HAP4 under respiratory growth. Biochem Biophys Res Commun 293:79–85CrossRefGoogle Scholar
  26. Rubin EM (2008) Genomics of cellulosic biofuels. Nature 454:841–845CrossRefGoogle Scholar
  27. Schmitt ME, Brown TA, Trumpower BL (1990) A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae. Nucleic Acids Res 18:3091–3092CrossRefGoogle Scholar
  28. Schüller C, Mamnun YM, Mollapour M, Krapf G, Schuster M, Bauer BE, Piper PW, Kuchler K (2004) Global phenotypic analysis and transcriptional profiling defines the weak acid stress response regulon in Saccharomyces cerevisiae. Mol Biol Cell 15:706–720CrossRefGoogle Scholar
  29. Shamir R, Maron-Katz A, Tanay A, Linhart C, Steinfeld I, Sharan R, Shiloh Y, Elkon R (2005) EXPANDER-an integrative program suite for microarray data analysis. BMC Bioinformatics 6:232CrossRefGoogle Scholar
  30. Taherzadeh MJ, Gustafsson L, Niklasson C, Liden G (1999) Conversion of furfural in aerobic and anaerobic batch fermentation of glucose by Saccharomyces cerevisiae. J Biosci Bioeng 87:169–174CrossRefGoogle Scholar
  31. Thomas KC, Hynes SH, Ingledew WM (2002) Influence of medium buffering capacity on inhibition of Saccharomyces cerevisiae growth by acetic and lactic acids. Appl Environ Microbiol 68:1616–1623CrossRefGoogle Scholar
  32. Ubiyvovk VM, Blazhenko OV, Gigot D, Penninckx M, Sibirny AA (2006) Role of gamma-glutamyltranspeptidase in detoxification of xenobiotics in the yeasts Hansenula polymorpha and Saccharomyces cerevisiae. Cell Biol Int 30:665–671CrossRefGoogle Scholar
  33. Xia JM, Yuan YJ (2009) Comparative lipidomics of four strains of Saccharomyces cerevisiae reveals different responses to furfural, phenol, and acetic acid. J Agric Food Chem 57:99–108CrossRefGoogle Scholar
  34. Zakrzewska A, Boorsma A, Brul S, Hellingwerf KJ, Klis FM (2005) Transcriptional response of Saccharomyces cerevisiae to the plasma membrane-perturbing compound chitosan. Eukaryot Cell 4:703–715CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Key Laboratory of Systems Bioengineering (Tianjin University), Ministry of Education, School of Chemical Engineering and TechnologyTianjin UniversityTianjinPeople’s Republic of China

Personalised recommendations