Zhao Xinqing, Zhang Mingming, Xu Guihong, Xu Jianren, Bai Fengwu
Sheng Wu Gong Cheng Xue Bao. 2014 Mar;30(3):368-80.
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.
工业微生物会受到各种应激条件的影响，包括产物和底物抑制。因此，提高应激耐受性对于工业微生物生产至关重要。乙酸是纤维素水解产物中的主要抑制剂之一，严重影响酿酒酵母的细胞生长和代谢。对酿酒酵母乙酸适应性反应和耐受性的分子机制进行研究，有助于培育出更强壮的工业酵母菌株，以实现更高效的生产。近年来，通过对全局基因表达和代谢组学分析，以及利用单基因缺失文库进行表型组学分析，人们对乙酸耐受性的分子机制有了更深入的了解。已鉴定出与乙酸反应和提高乙酸耐受性相关的新基因，并通过修饰关键基因构建了具有更高乙酸耐受性的新菌株。包括钾和锌在内的金属离子在酿酒酵母的乙酸耐受性中发挥着重要作用，锌的作用最早是在我们之前对絮凝酵母的研究中发现的。讨论了参与细胞壁重塑、膜运输、能量代谢、氨基酸生物合成和运输以及全局转录调控的基因。未来将在翻译后修饰、合成生物学和工程等层面进一步探索和修饰酵母乙酸耐受性的分子机制；所获得的知识将为培育更强壮的菌株，实现纤维素材料更高效生物转化以生产生物燃料和生物基化学品铺平道路。
