Applied Microbiology and Biotechnology

, Volume 93, Issue 3, pp 1207–1219 | Cite as

The effect of scale on gene expression: commercial versus laboratory wine fermentations

  • Debra Rossouw
  • Neil Jolly
  • Dan Jacobson
  • Florian F. BauerEmail author
Original Paper


Molecular and cellular processes that are responsible for industrially relevant phenotypes of fermenting microorganisms are a central focus of biotechnological research. Such research intends to generate insights and solutions for fermentation-based industries with regards to issues such as improving product yield or the quality of the final fermentation product. For logistical reasons, and to ensure data reproducibility, such research is mostly carried out in defined or synthetic media and in small-scale fermentation vessels. Two questions are frequently raised regarding the applicability of this approach to solve problems experienced in industrial fermentations: (1) Is synthetic medium a sufficiently accurate approximation of the generally more complex natural (and frequently highly variable) substrates that are employed in most fermentation-based industries, and (2) can results obtained in small-scale laboratory fermentations be extrapolated to large-scale industrial environments? Here, we address the second question through a comparative transcriptomic approach by assessing the response of an industrial wine yeast strain fermenting a natural grape juice in small-scale laboratory and large-scale industrial conditions. In yeast, transcriptome analysis is arguably the best available tool to holistically assess the physiological state of a population and its response to changing environmental conditions. The data suggest that scale does indeed impact on some environmental parameters such as oxygen availability. However, the data show that small-scale fermentations nevertheless accurately reflect general molecular processes and adaptations during large-scale fermentation and that extrapolation of laboratory datasets to real industrial processes can be justified.


Transcriptomics Scale Commercial wine fermentation 



Funding for the research presented in this paper was provided by the NRF (National Research Foundation, South Africa) and Winetech. We would also like to thank Jo McBride and the Cape Town Centre for Proteomic and Genomic Research for the microarray analysis and the staff and students at the IWBT for their support and assistance in numerous areas. Large-scale fermentations were carried out at the Nietvoorbij Research Cellars in collaboration with the ARC (Agricultural Research Council).

Supplementary material

253_2011_3564_MOESM1_ESM.docx (68 kb)
ESMdocx (DOCX 67 kb)


  1. Abbott DA, Knijnenburg TA, de Poorter LM, Reinders MJ, Pronk JT, van Maris AJ (2007) Generic and specific transcriptional responses to different weak organic acids in anaerobic chemostat cultures of Saccharomyces cerevisiae. FEMS Yeast Res 7:819–833CrossRefGoogle Scholar
  2. Abramova N, Sertil O, Mehta S, Lowry CV (2001) Reciprocal regulation of anaerobic and aerobic cell wall mannoprotein gene expression in Saccharomyces cereivisiae. J Bacteriol 183:2881–2887CrossRefGoogle Scholar
  3. Andréasson C, Neve EP, Ljungdahl PO (2004) Four permeases import proline and the toxic proline analogue azetidine-2-carboxylate into yeast. Yeast 21:193–199CrossRefGoogle Scholar
  4. Attfield PV (1997) Stress tolerance: the key to effective strains of baker’s yeast. Nat Biotechnol 15:1351–1357CrossRefGoogle Scholar
  5. Ben-Dor A, Shamir R, Yakhini Z (1999) Clustering gene expression patterns. J Comp Biol 6:281–297CrossRefGoogle Scholar
  6. Boer VM, de Winde JH, Pronk JT, Piper MD (2003) The genome-wide transcriptional responses of Saccharomyces cerevisiae grown on glucose in aerobic chemostat cultures limited for carbon, nitrogen, phosphorus or sulfur. J Biol Chem 278:3265–3274CrossRefGoogle Scholar
  7. Boulton RB, Singleton VL, Bisson LF, Kunkee RE (1996) Principles and practices of winemaking. Chapman & Hall, New York, pp 200–203Google Scholar
  8. Cramer G, Ergül A, Grimplet J, Tillett R, Tattersall E, Bohlman M, Vincent D, Sonderegger J, Evans J, Osborne C, Quilici D, Schlauch K, Schooley D, Cushman J (2007) Water and salinity stress in grape-vines: early and late changes in transcript and metabolite profiles. Funct Integr Genomics 7:111–134CrossRefGoogle Scholar
  9. Cullin C, Baudin-Baillieu A, Guillemet E, Ozier-Kalogeropoulos O (1996) Functional analysis of YCL09C: evidence for a role as the regulatory subunit of acetolactate synthase. Yeast 12:1511–1518CrossRefGoogle Scholar
  10. Da Silva FG, Iandolino A, Al-Kayal F, Bohlmann MC, Cushman Ma, Lim H, Ergul A, Figueroa R, Kabuloglu EK, Osborne C, Rowe J, Tattersall E, Leslie A, Xu J, Baek J, Cramer GR, Cushman JC, Cook DR (2005) Characterizing the grape transcriptome. Analysis of expressed sequence tags from multiple Vitis species and development of a compendium of gene expression during berry development. Plant Physiol 139:574–597Google Scholar
  11. Denis CL, Young ET (1983) Isolation and characterization of the positive regulatory gene ADR1 from Saccharomyces cerevisiae. Mol Cell Biol 3:360–370Google Scholar
  12. Dickinson JR, Salgado LE, Hewlins MJ (2003) The catabolism of amino acids to long chain and complex alcohols in Saccharomyces cerevisiae. J Biol Chem 278:8028–8034CrossRefGoogle Scholar
  13. Driesel A, Lommele A, Drescher B, Töpfer R, Bell M, Cartharius I, Cheutin N, Huck J-F, Kubiak J, Regnard P (2003) Towards the transcriptome of grapevine (Vitis vinifera L.). Acta Hort 603:239–250Google Scholar
  14. Duetz WA (2007) Microtiter plates as mini-bioreactors: miniaturization of fermentation methods. Trends Microbiol 15:469–475CrossRefGoogle Scholar
  15. Frezier V, Dubourdieu D (1992) Ecology of yeast strain Saccharomyces cerevisiae during spontaneous fermentation in a Bordeaux winery. Am J Enol Vitic 43:375–380Google Scholar
  16. Gasch AP, Werner-Washburne M (2002) The genomics of yeast responses to environmental stress and starvation. Funct Integr Genomics 2:181–192CrossRefGoogle Scholar
  17. Gasch A, Spellman P, Kao C, Carmel-Harel O, Eisen M, Storz G, Botstein D, Brown P (2000) Genomic expression changes in the response of yeast cells to environmental changes. Mol Biol Cell 11:4241–4257Google Scholar
  18. Huang HL, Brandriss MC (2000) The regulator of the yeast proline utilization pathway is differentially phosphorylated in response to the quality of the nitrogen source. Mol Cell Biol 20:892–899CrossRefGoogle Scholar
  19. Ideker T, Thorsson V, Ranish JA, Christmas R, Christmas R, Buhler J, Eng JK, Bumgarner R, Goodlett DR, Aebersold R, Hood L (2001) Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science 292:929–934CrossRefGoogle Scholar
  20. Iraqui I, Vissers S, Cartiaux M, Urrestarazu A (1998) Characterisation of Saccharomyces cerevisiae ARO8 and ARO9 genes encoding aromatic aminotransferases I and II reveals a new aminotransferase subfamily. Mol Gen Genet 257:238–248CrossRefGoogle Scholar
  21. Köffel R, Tiwari R, Falquet L, Schneiter R (2005) The Saccharomyces cerevisiae YLL012/YEH1, YLR020/YEH2, and TGL1 genes encode a novel family of membrane-anchored lipases that are required for steryl ester hydrolysis. Mol Cell Biol 25:1655–1668CrossRefGoogle Scholar
  22. Lamb DC, Kelly DE, Manning NJ, Kaderbhai MA, Kelly SL (1999) Biodiversity of the P450 catalytic cycle: yeast cytochrome b5/NADH cytochrome b5 reductase complex efficiently drives the entire sterol 14-demethylation (CYP51) reaction. FEBS Lett 462:283–288CrossRefGoogle Scholar
  23. Lambrechts MG, Pretorius IS (2000) Yeast and its importance to wine aroma. S Afr J Eno Vitic 21:97–129Google Scholar
  24. Lander ES (1999) Array of hope. Nat Genet 21:3–4CrossRefGoogle Scholar
  25. Landolfo S, Zara G, Zara S, Budroni M, Ciani M, Mannazzu I (2010) Oleic acid and ergosterol supplementation mitigates oxidative stress in wine strains of Saccharomyces cerevisiae. Int J Food Microbiol 141:229–235CrossRefGoogle Scholar
  26. Liccioli T, Tran TMT, Cozzolino D, Jiranek V, Chambers PJ, Schmidt SA (2011) Microvinification—how small can we go? Appl Microbiol Biotechnol 89:1621–1628CrossRefGoogle Scholar
  27. Mardia KV, Kent JT, Bibby JH (1979) Multivariate analysis. Academic, UKGoogle Scholar
  28. Marks VD, Ho Sui SJ, Erasmus D, van den Merwe GK, Brumm J, Wasserman WW, Bryan J, van Vuuren HJJ (2008) Dynamics of the yeast transcriptome during wine fermentation reveals a novel fermentation stress response. FEMS Yeast Res 8:35–52CrossRefGoogle Scholar
  29. Petersen JG, Kielland-Brandt MC, Nilsson-Tillgren T, Bornaes C, Holmberg S (1988) Molecular genetics of serine and threonine catabolism in Saccharomyces cerevisiae. Genetics 119:527–534Google Scholar
  30. Rossignol T, Dulau L, Julien A, Blondin B (2003) Genome-wide monitoring of wine yeast gene expression during alcoholic fermentation. Yeast 20:1369–1385CrossRefGoogle Scholar
  31. Rossouw D, Bauer FF (2009) Comparing the transcriptomes of wine yeast strains: toward understanding the interaction between environment and transcriptome during fermentation. Appl Microbiol Biotechnol 84:937–954CrossRefGoogle Scholar
  32. Rossouw D, Naes T, Bauer FF (2008) Linking gene regulation and the exo-metabolome: a comparative transcriptomics approach to identify genes that impact on the production of volatile aroma compounds in yeast. BMC Genomics 9:530CrossRefGoogle Scholar
  33. Rossouw D, Olivares-Hernandes R, Nielsen J, Bauer FF (2009) Comparative transcriptomic approach to investigate differences in wine yeast physiology and metabolism during fermentation. Appl Environ Microbiol 75:6600–6612CrossRefGoogle Scholar
  34. Rossouw D, van den Dool AH, Jacobson D, Bauer FF (2010) Comparative transcriptomic and proteomic profiling of industrial wine yeast strains. Appl Environ Microbiol 76:3911–3923CrossRefGoogle Scholar
  35. Shobayashi M, Mitsueda SI, Ago M, Fuji T, Iwashita K, Iefuji H (2005) Effects of culture conditions on ergosterol biosynthesis by Saccharomyces cerevisiae. Biosci Biotechnol Biochem 69:2381–2388CrossRefGoogle Scholar
  36. Smyth GK (2004) Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Molec Biol 3:3Google Scholar
  37. Tusher CG, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 98:5116–5121CrossRefGoogle Scholar
  38. Valachovic M, Hronská L, Hapala I (2001) Anaerobiosis induces complex changes in sterol esterification pattern in the yeast Saccharomyces cereivisiae. FEMS Microbiol Lett 197:41–45CrossRefGoogle Scholar
  39. Varela C, Cardenas J, Melo F, Agosin E (2005) Quantitative analysis of wine yeast gene expression profiles under winemaking conditions. Yeast 22:369–383CrossRefGoogle Scholar
  40. Vestrepen KJ, Van Laere SD, Vanderhaegen BM, Derdelinckx G, Dufour JP, Pretorius IS, Winderickx J, Thevelein JM, Delvaux FR (2003) Expression levels of the yeast alcohol acetyltransferase genes ATF1, Lg-ATF1, and ATF2 control the formation of a broad range of volatile esters. Appl Environ Microbiol 69:5228–5237Google Scholar
  41. Young ET, Dombek KM, Tachibana C, Ideker T (2003) Multiple pathways are co-regulated by the protein kinase Snf1 and the transcription factors Adr1 and Cat8. J Biol Chem 28:26146–26158CrossRefGoogle Scholar
  42. Zara G, Angelozzi D, Belviso S, Bardi L, Goffrini P, Lodi T, Budroni M, Mannazzu I (2009) Oxygen is required to restore flor strain viability and lipid biosynthesis under fermentative conditions. FEMS Yeast Res 9:217–225CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Debra Rossouw
    • 1
  • Neil Jolly
    • 2
  • Dan Jacobson
    • 1
  • Florian F. Bauer
    • 1
    Email author
  1. 1.Institute for Wine BiotechnologyUniversity of StellenboschStellenboschSouth Africa
  2. 2.ARC Infruitec-Nietvoorbij (The Fruit, Vine and Wine Institute of the Agricultural Research Council)StellenboschSouth Africa

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