Physiological and Molecular Characterization of an Oxidative Stress-Resistant Saccharomyces cerevisiae Strain Obtained by Evolutionary Engineering

Nazlı Kocaefe-Özşen, Bahtiyar Yilmaz, Ceren Alkım, Mevlüt Arslan, Alican Topaloğlu, Halil l̇brahim Kısakesen, Erdinç Gülsev, Z. Petek Çakar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Oxidative stress is a major stress type observed in yeast bioprocesses, resulting in a decrease in yeast growth, viability, and productivity. Thus, robust yeast strains with increased resistance to oxidative stress are in highly demand by the industry. In addition, oxidative stress is also associated with aging and age-related complex conditions such as cancer and neurodegenerative diseases. Saccharomyces cerevisiae, as a model eukaryote, has been used to study these complex eukaryotic processes. However, the molecular mechanisms underlying oxidative stress responses and resistance are unclear. In this study, we have employed evolutionary engineering (also known as adaptive laboratory evolution – ALE) strategies to obtain an oxidative stress-resistant and genetically stable S. cerevisiae strain. Comparative physiological, transcriptomic, and genomic analyses of the evolved strain were then performed with respect to the reference strain. The results show that the oxidative stress-resistant evolved strain was also cross-resistant against other types of stressors, including heat, freeze-thaw, ethanol, cobalt, iron, and salt. It was also found to have higher levels of trehalose and glycogen production. Further, comparative transcriptomic analysis showed an upregulation of many genes associated with the stress response, transport, carbohydrate, lipid and cofactor metabolic processes, protein phosphorylation, cell wall organization, and biogenesis. Genes that were downregulated included those related to ribosome and RNA processing, nuclear transport, tRNA, and cell cycle. Whole genome re-sequencing analysis of the evolved strain identified mutations in genes related to the stress response, cell wall organization, carbohydrate metabolism/transport, which are in line with the physiological and transcriptomic results, and may give insight toward the complex molecular mechanisms of oxidative stress resistance.

Original languageEnglish
Article number822864
JournalFrontiers in Microbiology
Volume13
DOIs
Publication statusPublished - 24 Feb 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Kocaefe-Özşen, Yilmaz, Alkım, Arslan, Topaloğlu, Kısakesen, Gülsev and Çakar.

Funding

This research was funded by the Scientific and Technological Research Council of Turkey, TUBITAK, (project no: 105T314, PI: ZC).

FundersFunder number
TUBITAK105T314
Türkiye Bilimsel ve Teknolojik Araştirma Kurumu

    Keywords

    • Saccharomyces cerevisiae
    • adaptive laboratory evolution
    • evolutionary engineering
    • genomic variants
    • heat preconditioning
    • oxidative stress
    • reactive oxygen species
    • stress resistance

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