eIF-5A调控酿酒酵母耐酸性的机制研究

有机酸发酵过程中的弱酸环境对生产菌的胁迫从而影响细胞状态及产物合成效率，是目前有机酸发酵产业亟需应对的问题。酿酒酵母的耐受特性在有机酸生产中占有很大的优势，实验室前期进化筛选出耐酸型酿酒酵母MTPfo-4（可耐受最低pH为2.44），通过比较野生型菌株与酸适应性进化菌株转录组差异，挖掘出新耐酸基因-翻译延伸因子eIF-5A。有研究报道eIF-5A在促进环境胁迫应答方面具有一定的调控作用，但具体调控机制尚不清楚。本项目拟从细胞微环境、转录和蛋白水平、代谢网络调控、细胞生理活性全面系统地阐明酿酒酵母抵御有机酸胁迫的生理应答新机制；在此基础上，提出相应的抵抗酸胁迫的代谢调控策略，结合基因工程技术构建重组耐酸菌株，以期达到微生物在酸胁迫过程中具有稳定的生理活性并提高细胞的耐酸活性的目标。本项目的研究思路及研究成果将解析酿酒酵母的耐酸新机制，还将为其他产酸菌的耐酸机制解析提供理论和方法学上的指导

The stress caused by the weak acid environment in the process of organic acid frmentation on the cell state of the production bacteria and the efficiency of product synthesis is an urgent problem in the organic acid fermentation industry. The tolerance characteristics of Saccharomyces cerevisiae occupies a great advantage in the production of organic acids. This project uses the acid-tolerant Saccharomyces cerevisiae MTPfo-4 (withstand a minimum pH of 2.44) selected by the laboratory's early evolution as a model strain. The transcriptome difference between the type strain and the acid-adapted evolutionary strain, the new acid-tolerant gene-translation elongation factor eIF-5A was discovered. Studies have reported that it has a certain regulatory role in promoting environmental stress response, but the specific regulatory mechanism is still unclear. From the perspective of cell microenvironment, transcription and protein levels, metabolic network regulation, and cell physiological activity, a new physiological response mechanism of Saccharomyces cerevisiae against organic acid stress is comprehensively and systematically elucidated; on this basis, corresponding metabolic regulation strategies to resist acid stress are proposed. Recombinant acid-tolerant strains are constructed by genetic engineering technology, in order to achieve the ultimate goal of microbes having stable physiological activity and maintaining relatively high biomass during acid stress. The research ideas and results of this project can not only enhance the new understanding of the acid stress mechanism of microorganisms, but also provide theoretical and methodological guidance for the analysis of the acid tolerance mechanism of other acid-producing bacteria.