Applied Microbiology and Biotechnology

, Volume 98, Issue 5, pp 2207–2221 | Cite as

Proteomic analysis reveals complex metabolic regulation in Saccharomyces cerevisiae cells against multiple inhibitors stress

  • Ya-Jin Lv
  • Xin Wang
  • Qian Ma
  • Xue Bai
  • Bing-Zhi LiEmail author
  • Weiwen Zhang
  • Ying-Jin Yuan
Genomics, transcriptomics, proteomics


Toxic compounds including acids, furans, and phenols (AFP) were generated from the pretreatment of lignocellulose. We cultivated Saccharomyces cerevisiae cells in a batch mode, besides the cell culture of original yeast strain in AFP-free medium which was referred as C0, three independent subcultures were cultivated under multiple inhibitors AFP and were referred as C1, C2, and C3 in time sequence. Comparing to C0, the cell density was lowered while the ethanol yield was maintained stably in the three yeast cultures under AFP stress, and the lag phase of C1 was extended while the lag phases of C2 and C3 were not extended. In proteomic analysis, 194 and 215 unique proteins were identified as differently expressed proteins at lag phase and exponential phase, respectively. Specifically, the yeast cells co-regulated protein folding and protein synthesis process to prevent the generation of misfolded proteins and to save cellular energy, they increased the activity of glycolysis, redirected metabolic flux towards phosphate pentose pathway and the biosynthesis of ethanol instead of the biosynthesis of glycerol and acetic acid, and they upregulated several oxidoreductases especially at lag phase and induced programmed cell death at exponential phase. When the yeast cells were cultivated under AFP stress, the new metabolism homeostasis in favor of cellular energy and redox homeostasis was generated in C1, then it was inherited and optimized in C2 and C3, enabling the yeast cells in C2 and C3 to enter the exponential phase in a short period after inoculation, which thus significantly shortened the fermentation time.


Saccharomyces cerevisiae Proteomic Bioethanol Inhibitor Tolerance Adaptation 



This work was financially supported by the National Natural Science Foundation of China (project numbers 21020102040 and 21106096) and the National Basic Research Program of MOST of China (“973” Program: 2013CB733601).

Supplementary material

253_2014_5519_MOESM1_ESM.xlsx (612 kb)
ESM 1 XLSX 611 kb


  1. Acar M, Becskei A, van Oudenaarden A (2005) Enhancement of cellular memory by reducing stochastic transitions. Nature 435(7039):228–232PubMedCrossRefGoogle Scholar
  2. Allen SA, Clark W, McCaffery JM, Cai Z, Lanctot A, Slininger PJ, Liu ZL, Gorsich SW (2010) Furfural induces reactive oxygen species accumulation and cellular damage in Saccharomyces cerevisiae. Biotechnol Biofuels 3:2PubMedCentralPubMedCrossRefGoogle Scholar
  3. Almeida JR, Bertilsson M, Gorwa-Grauslund MF, Gorsich S, Lidén G (2009) Metabolic effects of furaldehydes and impacts on biotechnological processes. Appl Microbiol Biotechnol 82(4):625–638PubMedCrossRefGoogle Scholar
  4. Alper H, Moxley J, Nevoigt E, Fink GR, Stephanopoulos G (2006) Engineering yeast transcription machinery for improved ethanol tolerance and production. Science 314(5805):1565–1568PubMedCrossRefGoogle Scholar
  5. Alriksson B, Horváth IS, Jönsson LJ (2010) Overexpression of Saccharomyces cerevisiae transcription factor and multidrug resistance genes conveys enhanced resistance to lignocellulose-derived fermentation inhibitors. Process Biochem 45(2):264–271CrossRefGoogle Scholar
  6. Attfield PV (1997) Stress tolerance: the key to effective strains of industrial baker’s yeast. Nat Biotechnol 15(13):1351–1357PubMedCrossRefGoogle Scholar
  7. Burrill DR, Silver PA (2010) Making cellular memories. Cell 140(1):13–18PubMedCentralPubMedCrossRefGoogle Scholar
  8. Cadière A, Ortiz-Julien A, Camarasa C, Dequin S (2011) Evolutionary engineered Saccharomyces cerevisiae wine yeast strains with increased in vivo flux through the pentose phosphate pathway. Metab Eng 13(3):263–271PubMedCrossRefGoogle Scholar
  9. Chong PK, Gan CS, Pham TK, Wright PC (2006) Isobaric tags for relative and absolute quantitation (iTRAQ) reproducibility: implication of multiple injections. J Proteome Res 5:1232–1240PubMedCrossRefGoogle Scholar
  10. Coleman ST, Fang TK, Rovinsky SA, Turano FJ, Moye-Rowley WS (2001) Expression of a glutamate decarboxylase homologue is required for normal oxidative stress tolerance in Saccharomyces cerevisiae. J Biol Chem 276(1):244–250PubMedCrossRefGoogle Scholar
  11. de Godoy LM, Olsen JV, Cox J, Nielsen ML, Hubner NC, Fröhlich F, Walther TC, Mann M (2008) Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast. Nature 455(7217):1251–1254PubMedCrossRefGoogle Scholar
  12. Delic M, Rebnegger C, Wanka F, Puxbaum V, Haberhauer-Troyer C, Hann S, Köllensperger G, Mattanovich D, Gasser B (2012) Oxidative protein folding and unfolded protein response elicit differing redox regulation in endoplasmic reticulum and cytosol of yeast. Free Radic Biol Med 52(9):2000–2012PubMedCrossRefGoogle Scholar
  13. DeLuna A, Avendano A, Riego L, Gonzalez A (2001) NADP-glutamate dehydrogenase isoenzymes of Saccharomyces cerevisiae. Purification, kinetic properties, and physiological roles. J Biol Chem 276(47):43775–43783PubMedCrossRefGoogle Scholar
  14. Destruelle M, Holzer H, Klionsky DJ (1994) Identification and characterization of a novel yeast gene: the YGP1 gene product is a highly glycosylated secreted protein that is synthesized in response to nutrient limitation. Mol Cell Biol 14(4):2740–2754PubMedCentralPubMedCrossRefGoogle Scholar
  15. Ding MZ, Wang X, Yang Y, Yuan YJ (2011a) Comparative metabolic profiling of parental and inhibitors-tolerant yeasts during lignocellulosic ethanol fermentation. Metabolomics 8(2):232–243CrossRefGoogle Scholar
  16. Ding MZ, Wang X, Yang Y, Yuan YJ (2011b) Metabolomic study of interactive effects of phenol, furfural, and acetic acid on Saccharomyces cerevisiae. OMICS 15(10):647–653PubMedCrossRefGoogle Scholar
  17. Ding MZ, Wang X, Liu W, Cheng JS, Yang Y, Yuan YJ (2012) Proteomic research reveals the stress response and detoxification of yeast to combined inhibitors. PLoS ONE 7(8):e43474PubMedCentralPubMedCrossRefGoogle Scholar
  18. Dinh TN, Nagahisa K, Hirasawa T, Furusawa C, Shimizu H (2008) Adaptation of Saccharomyces cerevisiae cells to high ethanol concentration and changes in fatty acid composition of membrane and cell size. PLoS ONE 3(7):e2623PubMedCentralPubMedCrossRefGoogle Scholar
  19. Ferreira RM, de Andrade LR, Dutra MB, de Souza MF, Flosi Paschoalin VM, Silva JT (2006) Purification and characterization of the chaperone-like Hsp26 from Saccharomyces cerevisiae. Protein Expres Purif 47(2):384–392CrossRefGoogle Scholar
  20. Fischer CR, Klein-Marcuschamer D, Stephanopoulos G (2008) Selection and optimization of microbial hosts for biofuels production. Metab Eng 10(6):295–304PubMedCrossRefGoogle Scholar
  21. Fraser HB, Moses AM, Schadt EE (2010) Evidence for widespread adaptive evolution of gene expression in budding yeast. Proc Natl Acad Sci U S A 107(7):2977–2982PubMedCentralPubMedCrossRefGoogle Scholar
  22. Gan CS, Chong PK, Pham TK, Wright PC (2007) Technical, experimental, and biological variations in isobaric tags for relative and absolute quantitation (iTRAQ). J Proteome Res 6:821–827PubMedCrossRefGoogle Scholar
  23. Garrido EO, Grant CM (2002) Role of thioredoxins in the response of Saccharomyces cerevisiae to oxidative stress induced by hydroperoxides. Mol Microbiol 43:993–1003PubMedCrossRefGoogle Scholar
  24. Gasch AP, Spellman PT, Kao CM, Carmel-Harel O, Eisen MB, Storz G, Botstein D, Brown PO (2000) Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 11(12):4241–4257PubMedCentralPubMedCrossRefGoogle Scholar
  25. Godon C, Lagniel G, Lee J, Buhler JM, Kieffer S, Perroti M, Boucheriei H, Toledano MB, Labarre J (1998) The H2O2 stimulon in Saccharomyces cerevisiae. J Biol Chem 273(35):22480–22489PubMedCrossRefGoogle Scholar
  26. 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(3):339–349PubMedCrossRefGoogle Scholar
  27. Grant CM (2001) Role of the glutathione/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions. Mol Microbiol 39:533–541PubMedCrossRefGoogle Scholar
  28. Grant CM (2008) Metabolic reconfiguration is a regulated response to oxidative stress. J Biol 7(1):1PubMedCentralPubMedCrossRefGoogle Scholar
  29. Guan Q, Haroon S, Bravo DG, Will JL, Gasch AP (2012) Cellular memory of acquired stress resistance in Saccharomyces cerevisiae. Genetics 192:495–505PubMedCrossRefGoogle Scholar
  30. Hampsey M, Singh BN, Ansari A, Lainé JP, Krishnamurthy S (2011) Control of eukaryotic gene expression: gene loops and transcriptional memory. Adv Enzyme Regul 51(1):118–125PubMedCentralPubMedCrossRefGoogle Scholar
  31. Hauser M, Horn P, Tournu H, Hauser NC, Hoheisel JD, Brown AJ, Dickinson JR (2007) A transcriptome analysis of isoamyl alcohol-induced filamentation in yeast reveals a novel role for Gre2p as isovaleraldehyde reductase. FEMS Yeast Res 7(1):84–92PubMedCrossRefGoogle Scholar
  32. Heer D, Heine D, Sauer U (2009) Resistance of Saccharomyces cerevisiae to high concentrations of furfural is based on NADPH-dependent reduction by at least two oxireductases. Appl Environ Microbiol 75(24):7631–7638PubMedCentralPubMedCrossRefGoogle Scholar
  33. Jung JY, Kim TY, Ng CY, Oh MK (2012) Characterization of GCY1 in Saccharomyces cerevisiae by metabolic profiling. J Appl Microbiol 113(6):1468–1478PubMedCrossRefGoogle Scholar
  34. Kang SW, Hegde RS (2008) Lighting up the stressed ER. Cell 135(5):787–789PubMedCentralPubMedCrossRefGoogle Scholar
  35. Kaufman RJ (2004) Regulation of mRNA translation by protein folding in the endoplasmic reticulum. Trends Biochem Sci 29(3):152–158PubMedCrossRefGoogle Scholar
  36. Keating JD, Panganiban C, Mansfield SD (2006) Tolerance and adaptation of ethanologenic yeasts to lignocellulosic inhibitory compounds. Biotechnol Bioeng 93(6):1196–1206PubMedCrossRefGoogle Scholar
  37. Kolkman A, Slijper M, Heck AJ (2005) Development and application of proteomics technologies in Saccharomyces cerevisiae. Trends Biotechnol 23(12):598–604PubMedCrossRefGoogle Scholar
  38. Krüger A, Grüning NM, Wamelink MM, Kerick M, Kirpy A, Parkhomchuk D, Bluemlein K, Schweiger MR, Soldatov A, Lehrach H, Jakobs C, Ralser M (2011) The pentose phosphate pathway is a metabolic redox sensor and regulates transcription during the antioxidant response. Antioxid Redox Signal 15(2):311–324PubMedCrossRefGoogle Scholar
  39. Kundu S, Peterson CL (2010) Dominant role for signal transduction in the transcriptional memory of yeast GAL genes. Mol Cell Biol 30(10):2330–2340PubMedCentralPubMedCrossRefGoogle Scholar
  40. Lempiäinen H, Shore D (2009) Growth control and ribosome biogenesis. Curr Opin Cell Biol 21(6):855–863PubMedCrossRefGoogle Scholar
  41. Li BZ, Yuan YJ (2010) Transcriptome shifts in response to furfural and acetic acid in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 86(6):1915–1924PubMedCrossRefGoogle Scholar
  42. 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(11):3765–3776PubMedCentralPubMedCrossRefGoogle Scholar
  43. Lin FM, Tan Y, Yuan YJ (2009b) Temporal quantitative proteomics of Saccharomyces cerevisiae in response to a nonlethal concentration of furfural. Proteomics 9(24):5471–5483PubMedCrossRefGoogle Scholar
  44. Liu ZH, Qin L, Jin MJ, Pang F, Li BZ, Kang Y, Dale BE, Yuan YJ (2013) Evaluation of storage methods for the conversion of corn stover to sugars based on steam explosion pretreatment. Bioresour Technol 132:5–15PubMedCrossRefGoogle Scholar
  45. Ma Q, Wang J, Lu S, Lv Y, Yuan Y (2012a) Quantitative proteomic profiling reveals photosynthesis responsible for inoculum size dependent variation in Chlorella sorokiniana. Biotechnol Bioeng 110(3):773–784PubMedCrossRefGoogle Scholar
  46. Ma Q, Zhang W, Zhang L, Qiao B, Pan C, Yi H, Wang L, Yuan YJ (2012b) Proteomic analysis of Ketogulonicigenium vulgare under glutathione reveals high demand for thiamin transport and antioxidant protection. PLoS ONE 7(2):e32156PubMedCentralPubMedCrossRefGoogle Scholar
  47. Ma Q, Zhou J, Zhang W, Meng X, Sun J, Yuan YJ (2011) Integrated proteomic and metabolomic analysis of an artificial microbial community for two-step production of vitamin C. PLoS ONE 6(10):e26108PubMedCentralPubMedCrossRefGoogle Scholar
  48. Madeo F, Engelhardt S, Herker E, Lehmann N, Maldener C, Proksch A, Wissing S, Fröhlich KU (2002) Apoptosis in yeast: a new model system with applications in cell biology and medicine. Curr Genet 41(4):208–216PubMedCrossRefGoogle Scholar
  49. Martinez A, Rodriguez ME, Wells ML, York SW, Preston JF, Ingram LO (2001) Detoxification of dilute acid hydrolysates of lignocellulose with lime. Biotechnol Progr 17:287–293CrossRefGoogle Scholar
  50. Matsufuji Y, Fujimura S, Ito T, Nishizawa M, Miyaji T, Nakagawa J, Ohyama T, Tomizuka N, Nakagawa T (2008) Acetaldehyde tolerance in Saccharomyces cerevisiae involves the pentose phosphate pathway and oleic acid biosynthesis. Yeast 25(11):825–833PubMedCrossRefGoogle Scholar
  51. Modig T, Almeida JR, Gorwa-Grauslund MF, Lidén G (2008) Variability of the response of Saccharomyces cerevisiae strains to lignocellulose hydrolysate. Biotechnol Bioeng 100(3):423–429PubMedCrossRefGoogle Scholar
  52. Modig T, Lidén G, Taherzadeh MJ (2002) Inhibition effects of furfural on alcohol dehydrogenase, aldehyde dehydrogenase and pyruvate dehydrogenase. Biochem J 363:769–776PubMedCrossRefGoogle Scholar
  53. Morano KA, Grant CM, Moye-Rowley WS (2012) The response to heat shock and oxidative stress in Saccharomyces cerevisiae. Genetics 190(4):1157–1195PubMedCrossRefGoogle Scholar
  54. Nelson DL, Cox MM (2009) Lehninger principles of biochemistry. Freeman, New YorkCrossRefGoogle Scholar
  55. Nwaka S, Kopp M, Holzer H (1995) Expression and function of the trehalase genes NTH1 and YBR0106 in Saccharomyces cerevisiae. J Biol Chem 270(17):10193–10198PubMedCrossRefGoogle Scholar
  56. Ogata Y, Charlesworth MC, Higgins L, Keegan BM, Vernino S, Muddiman DC (2007) Differential protein expression in male and female human lumbar cerebrospinal fluid using iTRAQ reagents after abundant protein depletion. Proteomics 7(20):3726–3734PubMedCrossRefGoogle Scholar
  57. Odat O, Matta S, Khalil H, Kampranis SC, Pfau R, Tsichlis PN, Makris AM (2007) Old yellow enzymes, highly homologous FMN oxidoreductases with modulating roles in oxidative stress and programmed cell death in yeast. J Biol Chem 282(49):36010–36023PubMedCrossRefGoogle Scholar
  58. Parawira W, Tekere M (2011) Biotechnological strategies to overcome inhibitors in lignocellulose hydrolysates for ethanol production: review. Crit Rev Biotechnol 31(1):20–31PubMedCrossRefGoogle Scholar
  59. Pham TK, Wright PC (2008) The proteomic response of Saccharomyces cerevisiae in very high glucose conditions with amino acid supplementation. J Proteome Res 7:4766–4774PubMedCrossRefGoogle Scholar
  60. Pham TK, Chong PK, Gan CS, Wright PC (2006) Proteomic analysis of Saccharomyces cerevisiae under high gravity conditions. J Proteome Res 5:3411–3419PubMedCrossRefGoogle Scholar
  61. Qin L, Liu ZH, Li BZ, Dale BE, Yuan YJ (2012) Mass balance and transformation of corn stover by pretreatment with different dilute organic acids. Bioresour Technol 112:319–326PubMedCrossRefGoogle Scholar
  62. Qin L, Liu ZH, Jin M, Li BZ, Yuan YJ (2013) High temperature aqueous ammonia pretreatment and post-washing enhance the high solids enzymatic hydrolysis of corn stover. Bioresour Technol 146:504–511PubMedCrossRefGoogle Scholar
  63. Ralser M, Heeren G, Breitenbach M, Lehrach H, Krobitsch S (2006) Triose phosphate isomerase deficiency is caused by altered dimerization-not catalytic inactivity-of the mutant enzymes. PLoS ONE 20(1):e30CrossRefGoogle Scholar
  64. Ralser M, Wamelink MM, Kowald A, Gerisch B, Heeren G, Struys EA, Klipp E, Jakobs C, Breitenbach M, Lehrach H, Krobitsch S (2007) Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress. J Biol 6(4):10PubMedCentralPubMedCrossRefGoogle Scholar
  65. Sárvári Horváth I, Franzén CJ, Taherzadeh MJ, Niklasson C, Lidén G (2003) Effects of furfural on the respiratory metabolism of Saccharomyces cerevisiae in glucose-limited chemostats. Appl Environ Microbiol 69(7):4076–4086PubMedCentralPubMedCrossRefGoogle Scholar
  66. Sales K, Brandt W, Rumbak E, Lindsey G (2000) The LEA-like protein HSP12 in Saccharomyces cerevisiae has a plasma membrane location and protects membranes against desiccation and ethanol-induced stress. Biochim Biophys Acta 1463(2):267–278PubMedCrossRefGoogle Scholar
  67. Salvadó Z, Chiva R, Rodríguez-Vargas S, Rández-Gil F, Mas A, Guillamón JM (2008) Proteomic evolution of a wine yeast during the first hours of fermentation. FEMS Yeast Res 8(7):1137–1146PubMedCrossRefGoogle Scholar
  68. Santangelo GM (2006) Glucose signaling in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 70(1):253–282PubMedCentralPubMedCrossRefGoogle Scholar
  69. Schröder M, Kaufman RJ (2005) ER stress and the unfolded protein response. Mutat Res 569(1–2):29–63PubMedCrossRefGoogle Scholar
  70. Seshi B (2006) An integrated approach to mapping the proteome of the human bone marrow stromal cell. Proteomics 6(19):5169–5182PubMedCrossRefGoogle Scholar
  71. Smits HP, Hauf J, Müller S, Hobley TJ, Zimmermann FK, Hahn-Hägerdal B, Nielsen J, Olsson L (2000) Simultaneous overexpression of enzymes of the lower part of glycolysis can enhance the fermentative capacity of Saccharomyces cerevisiae. Yeast 16(14):1325–1334CrossRefGoogle Scholar
  72. Sokolov S, Knorre D, Smirnova E, Markova O, Pozniakovsky A, Skulachev V, Severin F (2006) Ysp2 mediates death of yeast induced by amiodarone or intracellular acidification. Biochim Biophys Acta 1757(9–10):1366–1370PubMedCrossRefGoogle Scholar
  73. Steffen KK, McCormick MA, Pham KM, MacKay VL, Delaney JR, Murakami CJ, Kaeberlein M, Kennedy BK (2012) Ribosome deficiency protects against ER stress in Saccharomyces cerevisiae. Genetics 191(1):107–118PubMedCrossRefGoogle Scholar
  74. Swan TM, Watson K (1998) Stress tolerance in a yeast sterol auxotroph: role of ergosterol, heat shock proteins and trehalose. FEMS Microbiol Lett 169:191–197PubMedCrossRefGoogle Scholar
  75. Tirosh I, Wong KH, Barkai N, Struhl K (2011) Extensive divergence of yeast stress responses through transitions between induced and constitutive activation. Proc Natl Acad Sci U S A 108(40):16693–16698PubMedCentralPubMedCrossRefGoogle Scholar
  76. Trotter EW, Grant CM (2002) Thioredoxins are required for protection against a reductive stress in the yeast Saccharomyces cerevisiae. Mol Microbiol 46:869–878PubMedCrossRefGoogle Scholar
  77. Verghese J, Abrams J, Wang Y, Morano KA (2012) Biology of the heat shock response and protein chaperones: budding yeast (Saccharomyces cerevisiae) as a model system. Microbiol Mol Biol Rev 76(2):115–158PubMedCentralPubMedCrossRefGoogle Scholar
  78. Vogel C, Silva GM, Marcotte EM (2011) Protein expression regulation under oxidative stress. Mol Cell Proteomics 10(12):M111.009217PubMedCrossRefGoogle Scholar
  79. Walter P, Ron D (2011) The unfolded protein response: from stress pathway to homeostatic regulation. Science 334(6059):1081–1086PubMedCrossRefGoogle Scholar
  80. Wang X, Li BZ, Ding MZ, Zhang WW, Yuan YJ (2013) Metabolomic analysis reveals key metabolites related to the rapid adaptation of Saccharomyces cerevisiae to multiple inhibitors of furfural, acetic acid, and phenol. OMICS 17(3):150–159PubMedCrossRefGoogle Scholar
  81. Wang X, Jin M, Balan V, Jones AD, Xia L, Li BZ, Dale BE, Yuan YJ (2014) Comparative metabolic profiling revealed limitations in xylose-fermenting yeast during co-fermentation of glucose and xylose in the presence of inhibitors. Biotechnol Bioeng 111(1):152–164PubMedCrossRefGoogle Scholar
  82. Winkler J, Tyedmers J, Bukau B, Mogk A (2012) Hsp70 targets Hsp100 chaperones to substrates for protein disaggregation and prion fragmentation. J Cell Biol 198(3):387–404PubMedCrossRefGoogle Scholar
  83. 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 57:99–108PubMedCrossRefGoogle Scholar
  84. Yang J, Ding MZ, Li BZ, Liu ZL, Wang X, Yuan YJ (2012) Integrated phospholipidomics and transcriptomics analysis of Saccharomyces cerevisiae with enhanced tolerance to a mixture of acetic acid, furfural, and phenol. OMICS 16(7–8):374–386PubMedCrossRefGoogle Scholar
  85. Zacharioudakis I, Gligoris T, Tzamarias D (2007) A yeast catabolic enzyme controls transcriptional memory. Curr Biol 17(23):2041–2046PubMedCrossRefGoogle Scholar
  86. Zakrzewska A, van Eikenhorst G, Burggraaff JE, Vis DJ, Hoefsloot H, Delneri D, Oliver SG, Brul S, Smits GJ (2011) Genome-wide analysis of yeast stress survival and tolerance acquisition to analyze the central trade-off between growth rate and cellular robustness. Mol Biol Cell 22(22):4435–4446PubMedCentralPubMedCrossRefGoogle Scholar
  87. Zhao XQ, Bai FW (2009) Mechanisms of yeast stress tolerance and its manipulation for efficient fuel ethanol production. J Biotechnol 144(1):23–30PubMedCrossRefGoogle Scholar
  88. Zhong C, Cao YX, Li BZ, Yuan YJ (2010) Biofuels in China: past, present and future. Biofuel Bioprod Bior 4(3):326–342CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ya-Jin Lv
    • 1
    • 2
    • 3
  • Xin Wang
    • 1
    • 2
    • 3
  • Qian Ma
    • 1
    • 2
    • 3
  • Xue Bai
    • 1
    • 2
    • 3
  • Bing-Zhi Li
    • 1
    • 2
    • 3
    Email author
  • Weiwen Zhang
    • 1
    • 2
    • 3
  • Ying-Jin Yuan
    • 1
    • 2
    • 3
  1. 1.Key Laboratory of Systems Bioengineering, Ministry of EducationTianjin UniversityTianjinPeople’s Republic of China
  2. 2.School of Chemical Engineering and TechnologyTianjin UniversityTianjinPeople’s Republic of China
  3. 3.Collaborative Innovation Center of Chemical Science and Engineering (Tianjin)TianjinPeople’s Republic of China

Personalised recommendations