The study conducted under the leadership of ITU Molecular Biology and Genetics Department faculty member Prof. Dr. Zeynep Petek Çakar and based on application of a novel engineering approach “Evolutionary Engineering” to obtain stress resistant yeasts was puplished in one of the most prestigious journals in microbiology field Frontiers in Microbiology under the title of “Physiological and Molecular Characterization of an Oxidative Stress-Resistant Saccharomyces cerevisiae Strain Obtained by Evolutionary Engineering”.

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.