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

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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.

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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.

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Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Faculty of Science & Letters, Istanbul Technical University, Maslak, 34469, Istanbul, Turkey

    Yusuf Sürmeli, Can Holyavkin, Alican Topaloğlu, Mevlüt Arslan, Halil İbrahim Kısakesen & Zeynep Petek Çakar

  2. Dr. Orhan Öcalgiray Molecular Biology, Biotechnology and Genetics Research Center (İTÜ-MOBGAM), Istanbul Technical University, Maslak, 34469, Istanbul, Turkey

    Yusuf Sürmeli, Can Holyavkin, Alican Topaloğlu, Mevlüt Arslan, Halil İbrahim Kısakesen & Zeynep Petek Çakar

  3. Department of Agricultural Biotechnology, Faculty of Agriculture, Namık Kemal University, 59030, Tekirdağ, Turkey

    Yusuf Sürmeli

  4. Department of Genetics, Faculty of Veterinary Medicine, Van Yüzüncü Yıl University, 65080, Van, Turkey

    Mevlüt Arslan

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  1. Yusuf Sürmeli
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Sürmeli, Y., Holyavkin, C., Topaloğlu, A. et al. Evolutionary engineering and molecular characterization of a caffeine-resistant Saccharomyces cerevisiae strain. World J Microbiol Biotechnol 35, 183 (2019). https://doi.org/10.1007/s11274-019-2762-2

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