Skip to main content
Log in

Rationally designed perturbation factor drives evolution in Saccharomyces cerevisiae for industrial application

  • Fermentation, Cell Culture and Bioengineering - Original Paper
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Saccharomyces cerevisiae strains with favorable characteristics are preferred for application in industries. However, the current ability to reprogram a yeast cell on the genome scale is limited due to the complexity of yeast ploids. In this study, a method named genome replication engineering-assisted continuous evolution (GREACE) was proved efficient in engineering S. cerevisiae with different ploids. Through iterative cycles of culture coupled with selection, GREACE could continuously improve the target traits of yeast by accumulating beneficial genetic modification in genome. The application of GREACE greatly improved the tolerance of yeast against acetic acid compared with their parent strain. This method could also be employed to improve yeast aroma profile and the phenotype could be stably inherited to the offspring. Therefore, GREACE method was efficient in S. cerevisiae engineering and it could be further used to evolve yeast with other specific characteristics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Abyzov A, Urban AE, Snyder M, Gerstein M (2011) CNVnator: an approach to discover, genotype and characterize typical and atypical CNVs from family and population genome sequencing. Genome Res 21(6):974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Akada R (2002) Genetically modified industrial yeast ready for application. J Biosci Bioeng 94(6):536–544

    Article  CAS  PubMed  Google Scholar 

  3. Becker DM, Guarente L (1991) [12] High-efficiency transformation of yeast by electroporation. Methods Enzymol 194:182

    Article  CAS  PubMed  Google Scholar 

  4. Brown WC, Duncan JA, Campbell JL (1993) Purification and characterization of the Saccharomyces cerevisiae DNA polymerase delta overproduced in Escherichia coli. J Biol Chem 268(2):982–990

    CAS  PubMed  Google Scholar 

  5. Burgers PMJ, Gerik KJ (1998) Structure and processivity of two forms of Saccharomyces cerevisiae DNA polymerase δ. J Biol Chem 273(31):19756–19762

    Article  CAS  PubMed  Google Scholar 

  6. Cakar ZP, Turanliyildiz B, Alkim C, Yilmaz U (2012) Evolutionary engineering of Saccharomyces cerevisiae for improved industrially important properties. FEMS Yeast Res 12(2):171–182

    Article  CAS  PubMed  Google Scholar 

  7. Carey LB (2015) RNA polymerase errors cause splicing defects and can be regulated by differential expression of RNA polymerase subunits. Elife 4:e09945. https://doi.org/10.7554/eLife.09945

    Article  PubMed  PubMed Central  Google Scholar 

  8. Drake JW (1991) A constant rate of spontaneous mutation in DNA-based microbes. Proc Natl Acad Sci USA 88(16):7160–7164

    Article  CAS  PubMed  Google Scholar 

  9. Galli A, Chan CY, Parfenova L, Cervelli T, Schiestl RH (2015) Requirement of POL3 and POL4 on non-homologous and microhomology-mediated end joining in rad50/xrs2 mutants of Saccharomyces cerevisiae. Mutagenesis 30(6):841–849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Han DW (2003) Functional genetics of industrial yeasts; of ancient skills and modern applications. Top Curr Genet 2:1–16

    Article  Google Scholar 

  11. Herr AJ, Kennedy SR, Knowels GM, Schultz EM, Preston BD (2014) DNA replication error-induced extinction of diploid yeast. Genetics 196(3):677–691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hill JE, Myers AM, Koerner TJ, Tzagoloff A (1986) Yeast/E. coli shuttle vectors with multiple unique restriction sites. Yeast 2(3):163–167

    Article  CAS  PubMed  Google Scholar 

  13. Ho SN, Hunt HD, Horton RM, Pullen JK, Pease LR (1989) Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 77(1):51–59

    Article  CAS  PubMed  Google Scholar 

  14. Hou L (2009) Novel methods of genome shuffling in Saccharomyces cerevisiae. Biotechnol Lett 31(5):671–677

    Article  CAS  PubMed  Google Scholar 

  15. Husnik JI, Volschenk H, Bauer J, Colavizza D, Luo Z, van Vuuren HJ (2006) Metabolic engineering of malolactic wine yeast. Metab Eng 8(4):315–323

    Article  CAS  PubMed  Google Scholar 

  16. Johnson RE, Klassen R, Prakash L, Prakash S (2015) A major role of DNA polymerase delta in replication of both the leading and lagging DNA strands. Mol Cell 59(2):163–175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kozak BU, van Rossum HM, Niemeijer MS, van Dijk M, Benjamin K, Wu L et al (2016) Replacement of the initial steps of ethanol metabolism in Saccharomyces cerevisiae by ATP-independent acetylating acetaldehyde dehydrogenase. FEMS Yeast Res 16(2):fow006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25(14):1754–1760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Li H, Durbin R (2010) Fast and accurate long-read alignment with Burrows–Wheeler transform. Bioinformatics 26(5):589–595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N et al (2009) The sequence alignment/map format and SAMtools. Bioinformatics 25(16):2078–2079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Luan G, Bao G, Lin Z, Li Y, Chen Z, Li Y et al (2015) Comparative genome analysis of a thermotolerant Escherichia coli obtained by Genome Replication Engineering Assisted Continuous Evolution (GREACE) and its parent strain provides new understanding of microbial heat tolerance. New Biotechnol 32(6):732–738

    Article  CAS  Google Scholar 

  22. Luan G, Cai Z, Li Y, Ma Y (2013) Genome replication engineering assisted continuous evolution (GREACE) to improve microbial tolerance for biofuels production. Biotechnol Biofuels 6(1):137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lynch M (2010) Evolution of the mutation rate. Trends Genet 26(8):345–352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Morrison A, Johnson AL, Johnston LH, Sugino A (1993) Pathway correcting DNA replication errors in Saccharomyces cerevisiae. EMBO J 12(4):1467–1473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Morrison A, Sugino A (1992) Roles of POL3, POL2 and PMS1 genes in maintaining accurate DNA replication. Chromosoma 102(1):S147–S149

    Article  CAS  PubMed  Google Scholar 

  26. Netz DJ, Stith CM, Stumpfig M, Kopf G, Vogel D, Genau HM et al (2011) Eukaryotic DNA polymerases require an iron–sulfur cluster for the formation of active complexes. Nat Chem Biol 8(1):125–132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pires EJ, Teixeira JA, Branyik T, Vicente AA (2014) Yeast: the soul of beer’s aroma—a review of flavour-active esters and higher alcohols produced by the brewing yeast. Appl Microbiol Biotechnol 98(5):1937–1949

    Article  CAS  PubMed  Google Scholar 

  28. Replogle K, Hovland L, Rivier DH (1999) Designer deletion and prototrophic strains derived from Saccharomyces cerevisiae strain W303-1a. Yeast 15(11):1141–1149

    Article  CAS  PubMed  Google Scholar 

  29. Roohvand F, Shokri M, Abdollahpour-Alitappeh M, Ehsani P (2017) Biomedical applications of yeast—a patent view, part one: yeasts as workhorses for the production of therapeutics and vaccines. Expert Opin Ther Pat 27(8):929–951. https://doi.org/10.1080/13543776.2017.1339789

    Article  CAS  PubMed  Google Scholar 

  30. Rosche WA, Foster PL (2000) Determining mutation rates in bacterial populations. Methods 20(1):4–17. https://doi.org/10.1006/meth.1999.0901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Selmecki AM, Maruvka YE, Richmond PA, Guillet M, Shoresh N, Sorenson AL et al (2015) Polyploid can drive rapid adaptation in yeast. Nature 519(7543):349–352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shen N, Wang JJ, Liu CF, Li Y-X, Li Q (2013) Screening of brewer’s yeast with low acetaldehyde by directional domestication. Food Ferment Ind (in Chinese)

  33. Shi DJ, Wang CL, Wang KM (2009) Genome shuffling to improve thermotolerance, ethanol tolerance and ethanol productivity of Saccharomyces cerevisiae. J Ind Microbiol Biotechnol 36(1):139–147

    Article  CAS  PubMed  Google Scholar 

  34. Shiwa Y, Fukushimatanaka S, Kasahara K, Horiuchi T, Yoshikawa H (2012) Whole-genome profiling of a novel mutagenesis technique using proofreading-deficient DNA polymerase δ. Int J Evol Biol 2012:860797. https://doi.org/10.1155/2012/860797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Si T, HamediRad M, Zhao H (2015) Regulatory RNA-assisted genome engineering in microorganisms. Curr Opin Biotechnol 36:85–90

    Article  CAS  PubMed  Google Scholar 

  36. Si T, Luo Y, Bao Z, Zhao H (2015) RNAi-assisted genome evolution in Saccharomyces cerevisiae for complex phenotype engineering. ACS Synth Biol 4(3):283–291

    Article  CAS  PubMed  Google Scholar 

  37. Si T, Xiao H, Zhao H (2015) Rapid prototyping of microbial cell factories via genome-scale engineering. Biotechnol Adv 33(7):1420–1432

    Article  CAS  PubMed  Google Scholar 

  38. Skretas G, Kolisis FN (2012) Combinatorial approaches for inverse metabolic engineering applications. Comput Struct Biotechnol J 3:e201210021

    Article  PubMed  Google Scholar 

  39. Smith JD, Suresh S, Schlecht U, Wu M, Wagih O, Peltz G et al (2016) Quantitative CRISPR interference screens in yeast identify chemical–genetic interactions and new rules for guide RNA design. Genome Biol 17:45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Steensels J, Snoek T, Meersman E, Nicolino MP, Voordeckers K, Verstrepen KJ (2014) Improving industrial yeast strains: exploiting natural and artificial diversity. FEMS Microbiol Rev 38(5):947–995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Tokuriki N, Tawfik D (2009) Stability effects of mutations and protein evolvability. Curr Opin Struct Biol 19(5):596–604

    Article  CAS  PubMed  Google Scholar 

  42. Venkatesan RN, Hsu JJ, Lawrence NA, Preston BD, Loeb LA (2006) Mutator phenotypes caused by substitution at a conserved motif A residue in eukaryotic DNA polymerase delta. J Biol Chem 281(7):4486–4494

    Article  CAS  PubMed  Google Scholar 

  43. Wang J, Shen N, Yin H, Liu C, Li Y, Li Q (2013) Development of industrial brewing yeast with low acetaldehyde production and improved flavor stability. Appl Biochem Biotechnol 169(3):1016–1025

    Article  CAS  PubMed  Google Scholar 

  44. Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38(16):e164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wang ZY, Wang JJ, Liu XF, He XP, Zhang BR (2009) Recombinant industrial brewing yeast strains with ADH2 interruption using self-cloning GSH1 + CUP1 cassette. FEMS Yeast Res 9(4):574–581

    Article  CAS  PubMed  Google Scholar 

  46. Xu W, Wang J, Li Q (2014) Microarray studies on lager brewer’s yeasts reveal cell status in the process of autolysis. FEMS Yeast Res 14(5):714–728

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was financially supported by the National Science Foundation (nos. 31571942, and 31601558), the National High Technology Research and Development Program 863 (no. 2013AA102106-03), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Program of Introducing Talents of Discipline to Universities (no. 111-2-06), and the Fundamental Research Funds for the Central Universities (JUSRP51306A, JUSRP51402A and JUDCF13008).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Qi Li.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 1501 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, X., Liu, C., Niu, C. et al. Rationally designed perturbation factor drives evolution in Saccharomyces cerevisiae for industrial application. J Ind Microbiol Biotechnol 45, 869–880 (2018). https://doi.org/10.1007/s10295-018-2057-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10295-018-2057-x

Keywords

Navigation