Current Microbiology

, Volume 75, Issue 8, pp 1068–1076 | Cite as

A Transcriptomic Analysis of Saccharomyces cerevisiae Under the Stress of 2-Phenylethanol

  • Danfeng Jin
  • Bintao Gu
  • Dawei Xiong
  • Guochang Huang
  • Xiaoping Huang
  • Lan Liu
  • Jun Xiao


2-Phenylethanol (2-PE) is a kind of advanced aromatic alcohol with rose fragrance, which is wildly used for the deployment of flavors and fragrances. Microbial transformation is the most feasible method for the production of natural 2-PE. But a bottleneck problem is the toxicity of 2-PE on the cells. The molecular mechanisms of the toxic effect of 2-PE to Saccharomyces cerevisiae are not well studied. In this study, we analyzed the transcriptomes of S. cerevisiae in the media with and without 2-PE, respectively, using Illumina RNA-Seq technology. We identified 580 differentially expressed genes between S. cerevisiae in two different treatments. GO and KEGG enrichment analyses of these genes suggested that most genes encoding mitochondrial proteins, cytoplasmic, and plasma membrane proteins were significantly up-regulated, whereas the enzymes related to amino acid metabolism were down-regulated. These results indicated that 2-PE suppressed the synthesis of plasma membrane proteins, which suppressed the transport of nutrients required for growth. The findings in this study will provide insight into the inhibitory mechanism of 2-PE to yeast and other microbes.



This study was supported by the Science and Technology Project of Jiangxi Academy of Sciences (2017-YZD2-05, 2014-YYB-09, 2014-XTPH1-09).

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  1. 1.
    Albertazzi E, Cardillo R, Servi S, Zucchi G (1994) Biogeneration of 2-phenylethanol and 2-phenylethylacetate important aroma components. Biotechnol Lett 16:491–496CrossRefGoogle Scholar
  2. 2.
    Bauer MF, Hofmann S, Neupert W, Brunner M (2000) Protein translocation into mitochondria: the role of TIM complexes. Trends Cell Biol 10:25–31CrossRefPubMedGoogle Scholar
  3. 3.
    Boer VM, Tai SL, Vuralhan Z, Arifin Y, Walsh MC, Piper MD, de Winde JH, Pronk JT, Daran JM (2007) Transcriptional responses of Saccharomyces cerevisiae to preferred and nonpreferred nitrogen sources in glucose-limited chemostat cultures. FEMS Yeast Res 7:604–620CrossRefPubMedGoogle Scholar
  4. 4.
    Brush GS, Najor NA, Dombkowski AA, Cukovic D, Sawarynski KE (2012) Yeast IME2 functions early in meiosis upstream of cell cycle-regulated SBF and MBF targets. PLoS ONE 7:e31575CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Chung HJ, Lee SL, Chou CC (2000) Production and molar yield of 2-phenylethanol by Pichia fermentans L-5 as affected by some medium components. J Biosci Bioeng 90:142–147CrossRefPubMedGoogle Scholar
  6. 6.
    Desai N, Brown A, Amunts A, Ramakrishnan V (2017) The structure of the yeast mitochondrial ribosome. Science 355:528–531CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Eshkol N, Sendovski M, Bahalul M, Katz-Ezov T, Kashi Y, Fishman A (2009) Production of 2-phenylethanol from L-phenylalanine by a stress tolerant Saccharomyces cerevisiae strain. J Appl Microbiol 106:534–542CrossRefPubMedGoogle Scholar
  8. 8.
    Florea L, Song L, Salzberg SL (2013) Thousands of exon skipping events differentiate among splicing patterns in sixteen human tissues. F1000Research 2:188PubMedPubMedCentralGoogle Scholar
  9. 9.
    Godard P, Urrestarazu A, Vissers S, Kontos K, Bontempi G, van Helden J, Andre B (2007) Effect of 21 different nitrogen sources on global gene expression in the yeast Saccharomyces cerevisiae. Mol Cell Biol 27:3065–3086CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Hazelwood LA, Daran JM, van Maris AJ, Pronk JT, Dickinson JR (2008) The Ehrlich pathway for fusel alcohol production: a century of research on Saccharomyces cerevisiae metabolism. Appl Environ Microbiol 74:2259–2266CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Herrmann JM, Woellhaf MW, Bonnefoy N (2013) Control of protein synthesis in yeast mitochondria: the concept of translational activators. Biochim Biophys Acta 1833:286–294CrossRefPubMedGoogle Scholar
  12. 12.
    Hirschberg J, Simchen G (1977) Commitment to the mitotic cell cycle in yeast in relation to meiosis. Exp Cell Res 105:245–252CrossRefPubMedGoogle Scholar
  13. 13.
    Honigberg SM, Purnapatre K (2003) Signal pathway integration in the switch from the mitotic cell cycle to meiosis in yeast. J Cell Sci 11:2137–2147CrossRefGoogle Scholar
  14. 14.
    Hurtado S, Kim GK, Sontheimer EJ (2014) SPO24 is a transcriptionally dynamic, small ORF-encoding locus required for efficient sporulation in Saccharomyces cerevisiae. PLoS ONE 9:e105058CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Iraqui I, Vissers S, Andre B, Urrestarazu A (1999) Transcriptional induction by aromatic amino acids in Saccharomyces cerevisiae. Mol Cell Biol 19:3360–3371CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Jambhekar A, Amon A (2008) Control of meiosis by respiration. Curr Biol 18:969–975CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kim B, Cho BR, Hahn JS (2014) Metabolic engineering of Saccharomyces cerevisiae for the production of 2-phenylethanol via Ehrlich pathway. Biotechnol Bioeng 111:115–124CrossRefPubMedGoogle Scholar
  18. 18.
    Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL (2013) TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 14:R36CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Kuszak AJ, Jacobs D, Gurnev PA, Shiota T, Louis JM, Lithgow T, Bezrukov SM, Rostovtseva TK, Buchanan SK (2015) Evidence of distinct channel conformations and substrate binding affinities for the mitochondrial outer membrane protein translocase pore Tom40. J Biol Chem 290:26204–26217CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Liu P, Cheng Y, Yang M, Liu Y, Chen K, Long CA, Deng X (2014) Mechanisms of action for 2-phenylethanol isolated from Kloeckera apiculata in control of Penicillium molds of citrus fruits. BMC Microbiol 14:242CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Magasanik B (2003) Ammonia assimilation by Saccharomyces cerevisiae. Eukaryot Cell 2:827–829CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Marini AM, Vissers S, Urrestarazu A, Andre B (1994) Cloning and expression of the MEP1 gene encoding an ammonium transporter in Saccharomyces cerevisiae. EMBO J 13:3456–3463PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Neupert W (1997) Protein import into mitochondria. Annu Rev Biochem 66:863–917CrossRefPubMedGoogle Scholar
  24. 24.
    Piekarska I, Rytka J, Rempola B (2010) Regulation of sporulation in the yeast Saccharomyces cerevisiae. Acta Biochim Pol 57:241–250PubMedGoogle Scholar
  25. 25.
    Pierce M, Benjamin KR, Montano SP, Georgiadis MM, Winter E, Vershon AK (2003) Sum1 and Ndt80 proteins compete for binding to middle sporulation element sequences that control meiotic gene expression. Mol Cell Biol 23:4814–4825CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Popa CV, Dumitru I, Ruta LL, Danet AF, Farcasanu IC (2010) Exogenous oxidative stress induces Ca2+ release in the yeast Saccharomyces cerevisiae. FEBS J 277:4027–4038CrossRefPubMedGoogle Scholar
  27. 27.
    Reichert AS, Neupert W (2002) Contact sites between the outer and inner membrane of mitochondria-role in protein transport. Biochim Biophys Acta 1592:41–49CrossRefPubMedGoogle Scholar
  28. 28.
    Roy M, Reddy PH, Iijima M, Sesaki H (2015) Mitochondrial division and fusion in metabolism. Curr Opin Cell Biol 33:111–118CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Schuller HJ (2003) Transcriptional control of nonfermentative metabolism in the yeast Saccharomyces cerevisiae. Curr Genet 43:139–160PubMedGoogle Scholar
  30. 30.
    Sendovski M, Nir N, Fishman A (2010) Bioproduction of 2-phenylethanol in a biphasic ionic liquid aqueous system. J Agric Food Chem 58:2260–2265CrossRefPubMedGoogle Scholar
  31. 31.
    Serp D, von Stockar U, Marison IW (2003) Enhancement of 2-phenylethanol productivity by Saccharomyces cerevisiae in two-phase fed-batch fermentations using solvent immobilization. Biotechnol Bioeng 82:103–110CrossRefPubMedGoogle Scholar
  32. 32.
    Smith HE, Driscoll SE, Sia RA, Yuan HE, Mitchell AP (1993) Genetic evidence for transcriptional activation by the yeast IME1 gene product. Genetics 133:775–784PubMedPubMedCentralGoogle Scholar
  33. 33.
    Sokol AM, Sztolsztener ME, Wasilewski M, Heinz E, Chacinska A (2014) Mitochondrial protein translocases for survival and wellbeing. FEBS Lett 588:2484–2495CrossRefPubMedGoogle Scholar
  34. 34.
    Stark D, Munch T, Sonnleitner B, Marison IW, von Stockar U (2002) Extractive bioconversion of 2-phenylethanol from L-phenylalanine by Saccharomyces cerevisiae. Biotechnol Prog 18:514–523CrossRefPubMedGoogle Scholar
  35. 35.
    Stark D, Zala D, Münch T, Sonnleitner B, Marison IW, Stockar U (2003) Inhibition aspects of the bioconversion of L-phenylalanine to 2-phenylethanol by Saccharomyces cerevisiae. Enzyme Microb Technol 32:113–212CrossRefGoogle Scholar
  36. 36.
    Van der Rest ME, Kamminga AH, Nakano A, Anraku Y, Poolman B, Konings WN (1995) The plasma membrane of Saccharomyces cerevisiae: structure, function, and biogenesis. Microbiol Rev 59:304–322PubMedPubMedCentralGoogle Scholar
  37. 37.
    Walther K, Schuller HJ (2001) Adr1 and Cat8 synergistically activate the glucose-regulated alcohol dehydrogenase gene ADH2 of the yeast Saccharomyces cerevisiae. Microbiology 147:2037–2044CrossRefPubMedGoogle Scholar
  38. 38.
    Wang Z, Bai X, Guo X, He X (2017) Regulation of crucial enzymes and transcription factors on 2-phenylethanol biosynthesis via Ehrlich pathway in Saccharomyces cerevisiae. J Ind Microbiol Biotechnol 44:129–139CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of MicrobiologyJiangxi Academy of SciencesNanchangPeople’s Republic of China
  2. 2.The First Affiliated Hospital of Nanchang UniversityNanchangPeople’s Republic of China

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