化工进展

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嗜盐微生物底盘细胞:应用和前景

马悦原1,陈金春1,陈国强2   

  1. 1. 清华大学生命科学学院
    2. 清华大学生命科学学院;清华大学化工系
  • 收稿日期:2020-09-08 修回日期:2020-10-05 发布日期:2021-02-26
  • 通讯作者: 陈国强
  • 基金资助:
    重点研发计划;国家自然科学基金国际(地区)合作与交流项目NSFC-ANR项目(中法);国家自然科学基金 国际(地区)合作与交流项目

Halophilic Microorganisms as Microbial Chassis: Applications and Prospects

  • Received:2020-09-08 Revised:2020-10-05 Published:2021-02-26
  • Contact: Guo-Qiang -CHEN

摘要: 嗜盐微生物是一种耐高盐的微生物,有细菌、古菌、藻类等。其中的中度嗜盐菌耐受30-150克/升的氯化钠,有很高的研究价值和应用前景。嗜盐微生物可以在海水中生长,有的同时嗜碱,尤其不少嗜盐细菌在矿物培养基中生长迅速,具有作为底盘细胞的优势。随着近年来对嗜盐微生物分子操作工具的不断开发,嗜盐细菌的改造工作得到了迅猛的发展。工程化的嗜盐微生物已经可以用于合成数种聚羟基脂肪酸酯(PHA),也用于大规模生产多种聚合物、蛋白质、小分子化合物、氨基酸和化妆品原料。合成生物学技术的使用也使嗜盐微生物实现了可控形变, 有利于更多的胞内产物的合成和下游的细胞分离。根据嗜盐微生物,特别是嗜盐细菌的特点和研究进展,我们提出了以嗜盐微生物作为底盘细胞的“下一代工业生物技术”,使发酵工业实现了开放式的节能、节水、连续、全自动的过程,减少了微生物大规模培养的复杂程度和对设备的高要求,同时能联产生产多种产品,大幅度降低了工业生物技术的制造成本,提高了产品的竞争性。

关键词: 嗜盐微生物, 下一代工业生物技术, 聚羟基脂肪酸酯, PHA, 合成生物学, 生物反应器, 聚合物

Abstract: Halophilic microorganisms including halophilic bacteria, archaea and algae, can be grown under high salt concentration conditions. Among them, the mild halophiles tolerating 30-150 g/L NaCl are valuable for application purposes. Many halophiles can grow rapidly in seawater under alkali conditions in minimal media, and they are strong candidates as chassis for industrial purposes. Recently, more and more molecular tools and approaches have been developed for manipulating halophiles, resulting in a longer product pipeline including biopolymers, proteins, chemicals, amino acids and cosmetic ingredients. The use of synthetic biology methods allows controllable morphology changes of halophiles for more intracellular product formation and downstream separation of the cell. Based on the recent progresses of halophiles, especially halophilic bacteria, we propose the halophilic bacteria based “Next generation industrial biotechnology” (NGIB), which allows microbial fermentations to be conducted under open unsterile and continuous processes using seawater as a medium to save fresh water and energy for sterilization. Halophilic bacteria are more robust than other traditional microbial chassis. They can be full-automatic controlled under continuous way to maintain consistent growth conditions. The unsterile processes significantly reduce the process complexity and equipment cost, further enhancing the product competitiveness. Co-production of intracellular and extracellular molecules increase the economic benefits of the NGIB.

Key words: Halophile, Next Generation Industrial Biotechnology(NGIB), Polyhydroxyalkanoates, PHA, Synthetic biology, Bioreactors, Polymers

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