大肠杆菌乙酸耐受性菌株的构建及其耐受机制研究进展

Advances in construction of acetic acid tolerance Escherichia coli

乙酸是微生物发酵生产常见的副产物,也可作为碳源存在于木质纤维素水解液等非粮原料发酵培养基中。培养基中含有高浓度的乙酸/乙酸盐时会抑制细胞生长、降低生物量,影响目标产品的产量和产率。研究乙酸耐受性机制,改进菌株的乙酸耐受性,构建具有高乙酸耐受性工程菌株,对于以乙酸为碳源或利用含乙酸的原料进行高附加值产品发酵生产具有重要意义。本文综述了通过代谢工程、实验室适应性进化、全局转录机器工程和基于CRISPR可追踪基因组工程等方法构建大肠杆菌乙酸耐受性菌株的研究进展,进一步从乙酸同化代谢、氨基酸依赖型代谢、离子转运系统调节和细胞膜成分修饰等4个方面阐述了大肠杆菌乙酸耐受性菌株的耐受性应答机制,总结了大肠杆菌乙酸耐受菌株的生产应用,展望了提高大肠杆菌乙酸耐受方法和大肠杆菌乙酸耐受机制的研究方向。

Acetic acid is a promising carbon source,as a common by-product in microbial fermentation.It widely exists in non-food fermentation feedstock media such as lignin-cellulose hydrolysates.However,high concentrations of acetic acid or acetate in media inhibit cell growth,biomass,yield and productivity.It is significant to transform acetic acid into value-added chemicals efficiently through engineered strains with improved acetic acid tolerance.This paper reviews the state-of-the-art progresses in the strategies of improving Escherichia coli acetic acid tolerance via metabolic engineering,adaptive laboratory evolution,global transcription machine engineering and CRISPR traceable genome engineering.Furthermore,we summarize the acetic acid tolerance response mechanisms in E.coli,including acetic acid assimilation metabolism,amino acid-dependent metabolism,ion transport system regulation,and cell membrane component modification in E.coli.Finally,we discuss the application of improved acetic acid tolerance strains and the future direction in this field.