大肠杆菌的耐酸机制及其改造研究进展

Advances in acid-resistant mechanisms and modifications of Escherichia coli

摘要:

微生物细胞在自然环境或工业应用中经常受到酸胁迫，严重制约细胞生长性能和产物合成效率。为了在各种酸性环境中生存，耐酸细菌发展出多种保护机制来维持细胞内pH稳态，如氢离子消耗、细胞膜保护、代谢修饰等。因此，深入研究耐酸机制、改进菌株耐酸能力对于利用微生物发酵合成高附加值产品具有重要意义。作为模式微生物，大肠杆菌耐酸机制的研究较为透彻，近年来其耐酸性改造也取得了重大进展。本文主要总结了大肠杆菌的氧化或葡萄糖抑制系统(acid resistance system 1, AR1)、谷氨酸依赖型耐酸系统(acid resistance system 2, AR2)、精氨酸依赖型耐酸系统(acid resistance system 3, AR3)、赖氨酸依赖型耐酸系统(acid resistance system 4, AR4)和鸟氨酸依赖型耐酸系统(acid resistance system 5, AR5)、细胞膜保护以及生物大分子修复等方面的耐酸机制，并概述了利用传统代谢工程、全局转录工程和适应性实验室进化等方法构建大肠杆菌耐酸菌株的研究进展，同时展望了大肠杆菌耐酸机制及其改造的后续研究方向。

Abstract:

Microbial cells are often subjected to acid stress in natural environments or industrial applications, which severely restricts cell growth and product synthesis efficiency. In order to survive in acidic environments, acid-resistant bacteria have developed diverse protective mechanisms such as hydrogen ion consumption, membrane protection, and metabolic modification to maintain intracellular pH homeostasis. Therefore, in-depth research on acid-resistant mechanisms and improving acid resistance of strains are important for microbial biosynthesis of value-added products. As a model microorganism, Escherichia coli has been well studied regarding the acid-resistant mechanisms. In recent years, significant progress has been achieved in the research on the acid-resistant modification of E. coli. This paper reviews the acid-resistant mechanisms of E. coli in terms of oxidative or glucose-repressed system (acid resistance system 1, AR1), glutamate-dependent acid resistant system (acid resistance system 2, AR2), arginine-dependent acid resistant system (acid resistance system 3, AR3), lysine-dependent acid resistant system (acid resistance system 4, AR4), ornithine-dependent acid resistant system (acid resistance system 5, AR5), cell membrane protection, and biomolecular repair. Furthermore, we summarize the progress in constructing acid-resistant E. coli strains by metabolic engineering, global transcriptional engineering, and adaptive laboratory evolution. Finally, we discuss the subsequent research directions for further deciphering the acid-resistant mechanisms and improving acid resistance of E. coli.