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Evolutionary engineering and molecular characterization of a caffeine-resistant Saccharomyces cerevisiae strain

  • Yusuf Sürmeli
  • Can Holyavkin
  • Alican Topaloğlu
  • Mevlüt Arslan
  • Halil İbrahim Kısakesen
  • Zeynep Petek ÇakarEmail author
Original Paper
  • 127 Downloads

Abstract

Caffeine is a naturally occurring alkaloid, where its major consumption occurs with beverages such as coffee, soft drinks and tea. Despite a variety of reports on the effects of caffeine on diverse organisms including yeast, the complex molecular basis of caffeine resistance and response has yet to be understood. In this study, a caffeine-hyperresistant and genetically stable Saccharomyces cerevisiae mutant was obtained for the first time by evolutionary engineering, using batch selection in the presence of gradually increased caffeine stress levels and without any mutagenesis of the initial population prior to selection. The selected mutant could resist up to 50 mM caffeine, a level, to our knowledge, that has not been reported for S. cerevisiae so far. The mutant was also resistant to the cell wall-damaging agent lyticase, and it showed cross-resistance against various compounds such as rapamycin, antimycin, coniferyl aldehyde and cycloheximide. Comparative transcriptomic analysis results revealed that the genes involved in the energy conservation and production pathways, and pleiotropic drug resistance were overexpressed. Whole genome re-sequencing identified single nucleotide polymorphisms in only three genes of the caffeine-hyperresistant mutant; PDR1, PDR5 and RIM8, which may play a potential role in caffeine-hyperresistance.

Graphic abstract

Keywords

Adaptive laboratory evolution Caffeine Evolutionary engineering Pleiotropic drug resistance (PDR) Saccharomyces cerevisiae Stress resistance 

Notes

Acknowledgements

We thank Levent Üge for technical assistance with HPLC analyses, and our former and present students Ogün Morkoç, Gizem Karabıyık, Diler Kaan Atmaca, and İsmail Can Karaoğlu for their help with the physiological experiments. We also thank Cihan Erdinç Gülsev and Nazlı Kocaefe for technical assistance with the whole genome re-sequencing experiments, Burcu Hacısalihoğlu for fruitful discussions and experimental assistance, Prof. Dr. Oğuz Öztürk for providing propolis and Prof. Dr. Nevin Gül Karagüler for her helpful comments regarding our SNP data.

Funding

The authors received no financial support for the research presented in this article.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11274_2019_2762_MOESM1_ESM.docx (20 kb)
Supplementary file1 (DOCX 20 kb)

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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Molecular Biology and Genetics, Faculty of Science & LettersIstanbul Technical UniversityIstanbulTurkey
  2. 2.Dr. Orhan Öcalgiray Molecular Biology, Biotechnology and Genetics Research Center (İTÜ-MOBGAM)Istanbul Technical UniversityIstanbulTurkey
  3. 3.Department of Agricultural Biotechnology, Faculty of AgricultureNamık Kemal UniversityTekirdağTurkey
  4. 4.Department of Genetics, Faculty of Veterinary MedicineVan Yüzüncü Yıl UniversityVanTurkey

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