酿酒酵母乙酸耐性分子机制的功能基因组进展

Advances in functional genomics studies underlying acetic acid tolerance of Saccharomyces cerevisiae

摘要:

提高工业酿酒酵母对高浓度代谢产物及原料中的毒性底物等环境胁迫因素的耐受性，对提高工业生产效率具有重要的意义。乙酸是纤维素原料水解产生的主要毒性副产物之一，其对酵母细胞的生长和代谢都具有较强的抑制作用，因此，对酿酒酵母乙酸耐性分子机制的研究可为选育优良菌种提供理论依据。近年来，通过细胞全局基因表达分析和代谢组分析，以及对单基因敲除的所有突变体的表型组研究，对酿酒酵母乙酸耐性的分子机制有了更多新的认识，揭示了很多新的与乙酸毒性适应性反应和乙酸耐性提高相关的基因。综述了近年来酿酒酵母乙酸耐性的基因组规模的研究进展，以及在此基础上构建乙酸耐性提高的工业酵母菌的代谢工程操作。结合本课题组的研究，对金属离子锌在酿酒酵母乙酸耐性中的作用进行了深入分析。未来对酿酒酵母乙酸耐性分子机理的认识及改造将深入到翻译后修饰和合成生物学等新的水平，所获得的认知，将为选育可高效进行纤维素原料生物转化、高效生产生物燃料和生物基化学品的工业酿酒酵母的菌株奠定理论基础。

Abstract:

Industrial microorganisms are subject to various stress conditions, including products and substrates inhibitions. Therefore, improvement of stress tolerance is of great importance for industrial microbial production. Acetic acid is one of the major inhibitors in the cellulosic hydrolysates, which affects seriously on cell growth and metabolism of Saccharomyces cerevisiae. Studies on the molecular mechanisms underlying adaptive response and tolerance of acetic acid of S. cerevisiae benefit breeding of robust strains of industrial yeast for more efficient production. In recent years, more insights into the molecular mechanisms underlying acetic acid tolerance have been revealed through analysis of global gene expression and metabolomics analysis, as well as phenomics analysis by single gene deletion libraries. Novel genes related to response to acetic acid and improvement of acetic acid tolerance have been identified, and novel strains with improved acetic acid tolerance were constructed by modifying key genes. Metal ions including potassium and zinc play important roles in acetic acid tolerance in S. cerevisiae, and the effect of zinc was first discovered in our previous studies on flocculating yeast. Genes involved in cell wall remodeling, membrane transport, energy metabolism, amino acid biosynthesis and transport, as well as global transcription regulation were discussed. Exploration and modification of the molecular mechanisms of yeast acetic acid tolerance will be done further on levels such as post-translational modifications and synthetic biology and engineering; and the knowledge obtained will pave the way for breeding robust strains for more efficient bioconversion of cellulosic materials to produce biofuels and bio-based chemicals.