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.
Highlights
In all aerobic organisms, the generation of reactive oxygen species (ROS), as side products of cellular metabolism, including hydrogen peroxide (H2O2), the hydroxyl radical (.OH), or superoxide anions (O2−) by reduction of molecular oxygen is an inevitable aspect of life (Jamieson, 1992; Izawa et al, 1995; Bayliak et al, 2017)
As the growth of the 21st–24th populations was as low as 0.1–0.4 optical density measurements at 600 nm (OD600), the selection experiments to obtain oxidative stress-resistant evolved strains ended with these final populations
We investigated the genetic and molecular mechanisms that provide yeast cells an advantage over previous generations to cope with this stress condition (Gasch et al, 2000; Alexandre et al, 2001; Morano et al, 2012)
Summary
The generation of reactive oxygen species (ROS), as side products of cellular metabolism, including hydrogen peroxide (H2O2), the hydroxyl radical (.OH), or superoxide anions (O2−) by reduction of molecular oxygen is an inevitable aspect of life (Jamieson, 1992; Izawa et al, 1995; Bayliak et al, 2017). As plants are sedentary organisms and possess photosynthetic systems, they cannot move to find optimal conditions and they produce a lot of ROS. They balance the overoxidation and overreduction with short term and long-term mechanisms, including enzymatic systems (Lushchak, 2011). About 90% of the ATP is generated via oxidative phosphorylation and is the primary source of ROS in cells (Candas and Li, 2014). When antioxidant defenses are overwhelmed and unable to counteract ROS, the resulting oxidative stress (Finkel and Holbrook, 2000; Finkel, 2005) can damage nucleic acids, oxidize amino acids, as well as co-factors of proteins, and disturb cellular homeostasis (Imlay, 2015)
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