基于极端微生物的生物制造

邵明威; 孙思勉; 杨时茂; 陈国强

doi:10.12211/2096-8280.2024-016

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基于极端微生物的生物制造

特约评述 | 更新时间：2025-04-11

- 基于极端微生物的生物制造
- Bioproduction based on extremophiles
- 合成生物学 2024年5卷第6期页码：1419-1436
- 作者机构：
  
  1.清华大学生命科学学院，北京 100084
  2.清华大学合成与系统生物学中心，北京 100084
  3.清华大学化学工程系，教育部工业生物催化重点实验室，北京 100084
- 作者简介：
  
  [ "邵明威（2001—），男，博士研究生。研究方向为盐单胞菌进化系统构建与应用。E-mail：shaomingwei@phalab.org" ]
  [ "陈国强（1963—），男，博士，教授。研究方向为微生物聚羟基脂肪酸酯（PHA）的合成、代谢和应用。E-mail：chengq@mail.tsinghua.edu.cn" ]
- 基金信息：
  
  国家自然科学基金(32130001;21761132013;31771886;31971170)
- DOI：10.12211/2096-8280.2024-016
  中图分类号： Q816
- 收稿：2024-02-04，
  
  修回：2024-04-27，
  
  纸质出版：2024-12-31
- 稿件说明：
移动端阅览
邵明威，孙思勉，杨时茂，陈国强. 基于极端微生物的生物制造［J］. 合成生物学， 2024， 5（6）： 1419-1436

SHAO Mingwei， SUN Simian， YANG Shimao， CHEN Guoqiang. Bioproduction based on extremophiles［J］. Synthetic Biology Journal， 2024， 5（6）： 1419-1436
邵明威，孙思勉，杨时茂，陈国强. 基于极端微生物的生物制造［J］. 合成生物学， 2024， 5（6）： 1419-1436 DOI： 10.12211/2096-8280.2024-016.

SHAO Mingwei， SUN Simian， YANG Shimao， CHEN Guoqiang. Bioproduction based on extremophiles［J］. Synthetic Biology Journal， 2024， 5（6）： 1419-1436 DOI： 10.12211/2096-8280.2024-016.

摘要

以微生物或酶为基础的生物制造，正以其绿色、环保、可持续等优势逐渐替代以化石燃料为原料的传统化工生产模式。然而，传统工业生物技术存在易染菌、设备复杂、难以连续发酵等劣势。相较而言，“下一代工业生物技术”（NGIB）利用以嗜盐菌、嗜热菌和嗜酸碱菌等极端微生物作为底盘细胞，使用廉价底物生产多种高附加值产品，具有开放、无需灭菌、连续发酵等优点。本文介绍了嗜盐菌、嗜热菌和嗜酸碱菌极端微生物的定义以及在高盐、高温、极度酸碱等极端环境下快速生长的特性。随后总结了目前极端微生物的基因工程手段例如启动子工程、以CRISPR为代表的基因编辑技术、命运共同体策略、稳定质粒载体等，代谢工程手段例如增加碳源前体、敲除旁路代谢、减少副产物、提高转运等，以及极端微生物生产的多种产品例如PHA、蛋白质、氨基酸及小分子衍生物等。同时概括了目前在极端微生物底盘细胞改造过程中仍存在的问题，如缺乏多种优秀的质粒载体、质粒转化效率低、缺乏高效基因编辑技术以及其他非嗜盐菌生长发酵周期较长等，并提出了相应的解决策略。最后展望了如何充分利用不同类型极端微生物的特性生产优势产品，推动下一代工业生物技术的发展与完善，实现绿色、环保、可持续的生物制造。

Abstract

The traditional chemical manufacturing based on petroleum as raw material has had profound impacts in the development of modern society. However

it also has many drawbacks

such as environmental pollution and lack of sustainability. In contrast

biomanufacture with microorganisms as industrial chassis is gradually becoming a hot spot in industrial production due to its advantages of environmental friendliness and sustainability. Nonetheless

the limitations of traditional industrial biotechnology

including susceptibility to microbial contamination

complex fermentation processes

and difficulties in achieving co

ntinuous fermentations

have hindered the competitiveness of their products in terms of production costs compared to chemical industries To address these challenges

“Next Generation Industrial Biotechnology” (NGIB) with extremophiles as non-conventional chassis

has been undergoing continuous development with increasing global attentions.The basis of NGIB is extremophiles

such as halophiles

acidophiles

and thermophiles

known for their ability to thrive in extreme environments. Through molecular engineering of extremophiles

especially

Halomonas

spp.

the recombinants can utilize various inexpensive carbon sources for continuous open fermentation

leading to the production of diverse high-value products with reduced cost. This review defines and summarizes the characteristics of extremophiles

highlighting their ability to grow rapidly in extreme environments like high salt

high temperature

and extreme pH. Subsequently

the review summarizes current genetic engineering approaches for extremophiles

such as promoter engineering

CRISPR-based gene editing

community fate strategy

and stable plasmid vectors. Additionally

metabolic engineering methods such as precursor supplementation

pathway disruption

byproduct reduction

and enhanced transport are discussed

along with various products including PHA

proteins

amino acids

and small molecule derivatives. The review also identifies challenges in extremophile engineering

such as the lack of suitable plasmid vectors

low plasmid transformation efficiency

lack of efficient gene editing tools

and long growth and fermentation cycle

but proposes corresponding solutions. Finally

the review proposes leveraging the characteristics of different types of extremophiles to produce advantageous products

thereby driving the development of next generation industrial biotechnology based on various extremphiles

and achieving green

environmentally friendly

and sustainable biomanufacturing.

关键词

Keywords

references

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