Association of improved oxidative stress tolerance and alleviation of glucose repression with superior xylose-utilization capability by a natural isolate of <italic>Saccharomyces cerevisiae</italic>.

Background: <italic>Saccharomyces cerevisiae</italic> wild strains generally have poor xylose-utilization capability, which is a major barrier for efficient bioconversion of lignocellulosic biomass. Laboratory adaption is commonly used to enhance xylose utilization of recombinant <italic>S. cerevisiae</italic>. Apparently, yeast cells could remodel the metabolic network for xylose metabolism. However, it still remains unclear why natural isolates of <italic>S. cerevisiae</italic> poorly utilize xylose. Here, we analyzed a unique <italic>S. cerevisiae</italic> natural isolate YB-2625 which has superior xylose metabolism capability in the presence of mixed-sugar. Comparative transcriptomic analysis was performed using <italic>S. cerevisiae</italic> YB-2625 grown in a mixture of glucose and xylose, and the model yeast strain S288C served as a control. Global gene transcription was compared at both the early mixed-sugar utilization stage and the latter xylose-utilization stage. Results: Genes involved in endogenous xylose-assimilation (<italic>XYL2</italic> and <italic>XKS1</italic>), gluconeogenesis, and TCA cycle showed higher transcription levels in <italic>S. cerevisiae</italic> YB-2625 at the xylose-utilization stage, when compared to the reference strain. On the other hand, transcription factor encoding genes involved in regulation of glucose repression (<italic>MIG1</italic>, <italic>MIG2</italic>, and <italic>MIG3</italic>) as well as <italic>HXK2</italic> displayed decreased transcriptional levels in YB-2625, suggesting the alleviation of glucose repression of <italic>S. cerevisiae</italic> YB-2625. Notably, genes encoding antioxidant enzymes (<italic>CTT1</italic>, <italic>CTA1</italic>, <italic>SOD2,</italic> and <italic>PRX1</italic>) showed higher transcription levels in <italic>S. cerevisiae</italic> YB-2625 in the xylose-utilization stage than that of the reference strain. Consistently, catalase activity of YB-2625 was 1.9-fold higher than that of <italic>S. cerevisiae</italic> S288C during the xylose-utilization stage. As a result, intracellular reactive oxygen species levels of <italic>S. cerevisiae</italic> YB-2625 were 43.3 and 58.6% lower than that of S288C at both sugar utilization stages. Overexpression of <italic>CTT1</italic> and <italic>PRX1</italic> in the recombinant strain <italic>S. cerevisiae</italic> YRH396 deriving from <italic>S. cerevisiae</italic> YB-2625 increased cell growth when xylose was used as the sole carbon source, leading to 13.5 and 18.1%, respectively, more xylose consumption. Conclusions: Enhanced oxidative stress tolerance and relief of glucose repression are proposed to be two major mechanisms for superior xylose utilization by <italic>S. cerevisiae</italic> YB-2625. The present study provides insights into the innate regulatory mechanisms underlying xylose utilization in wild-type <italic>S. cerevisiae</italic>, which benefits the rapid development of robust yeast strains for lignocellulosic biorefineries. [ABSTRACT FROM AUTHOR]