组蛋白修饰酶Set5p调控酿酒酵母抗逆性的机理及高效菌株构建

秸秆等木质纤维素类生物质预处理产生的抑制物及其他发酵相关逆境条件对酿酒酵母生长和代谢的抑制，是影响发酵效率的关键。转录因子和染色质蛋白都参与酵母基因表达调控，现有研究多集中在转录因子，对染色质蛋白的研究少有报道。组蛋白修饰可影响转录因子和DNA结合，从而影响基因表达，然而目前对组蛋白修饰酶调控发酵相关抗逆性的研究还有待深入。前期研究发现，组蛋白甲基转移酶Set5p过表达可明显提高酿酒酵母对多种逆境环境的耐受性，而且Set5p的表达在胁迫条件下可高度激活，但其分子机理未知。本课题拟研究Set5p在逆境胁迫条件下的激活机制，揭示Set5p的作用靶点和调控网络，以及长期胁迫条件下Set5p表达水平对代谢的影响，进一步结合高效菌株构建和过程优化，提高纤维素乙醇的发酵效率。预期所取得的研究进展，可加深对酿酒酵母抗逆相关基因调控机制的理解，为进一步提高纤维素生物质水解糖转化效率提供基础。

Inhibition in yeast cell growth and fermentation performance by toxic byproducts generated during the pretreatment of lignocellulosic biomass as well as other fermentation-related environmental stresses is a key factor to affect fermentation efficiency of sugars in the hydrolysate. Both transcription factors and chromatin proteins regulate gene transcription in yeast cells. Currently, most studies focus on transcription factors, whereas very few studies are with chromatin proteins. Histone modification affects the binding of transcription factor with DNA, and consequently exerts significant impact on gene expression. However, in-depth studies on histone modification and yeast stress tolerance are scarce. Our preliminary research found that overexpression of the histone methyltransferase Set5p significantly improved stress tolerance of the budding yeast Saccharomyces cerevisiae to multiple environmental stresses, and self-activation of Set5p under stressful conditions was also observed. However, the underlying mechanism remains unclear. In this project, mechanism underlying the self-activation of Set5p will be explored, and the targets for Set5p to respond environmental stresses as well as the regulatory network will be identified. Furthermore, metabolic regulation by the expression levels of Set5p under long-term stressful environments related to industrial applications will be investigated for strain development, which together with process optimization will ultimately improve cellulosic ethanol production. The progress achieved in this study will enrich the knowledge on the regulation of gene expression in the presence of various stresses. In addition, the results will benefit more efficient bioconversion of lignocellulosic biomass with improved yield.