合成生物技术驱动酪丁酸梭菌细胞工厂开发的研究进展

刘家宇; 杨智晗; 杨蕾; 朱丽英; 朱政明; 江凌

doi:10.12211/2096-8280.2022-022

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合成生物技术驱动酪丁酸梭菌细胞工厂开发的研究进展

特约评述 | 更新时间：2026-01-19

- 合成生物技术驱动酪丁酸梭菌细胞工厂开发的研究进展
- Advances in the development of Clostridium tyrobutyricum cell factories driven by synthetic biotechnology
- 合成生物学 2022年3卷第6期页码：1174-1200
- 作者机构：
  
  1.南京工业大学食品与轻工学院，江苏南京 211816
  2.南京工业大学生物与制药工程学院，江苏南京 211816
  3.南京工业大学化学与分子工程学院，江苏南京 211816
  4.南京工业大学材料化学工程国家重点实验室，江苏南京 211816
- 作者简介：
  
  [ "刘家宇（1998—），男，硕士研究生。研究方向为微生物系统与合成生物学。E-mail：liujoy@njtech.edu.cn" ]
  [ "朱政明（1989—），男，博士，副教授。研究方向为微生物系统与合成生物学。E-mail：zhuzm@njtech.edu.cn" ]
  [ "江凌（1982—），男，博士，教授。研究方向为发酵工程与酶工程。E-mail：jiangling@njtech.edu.cn" ]
- 基金信息：
  
  国家自然科学基金优秀青年科学基金项目(31922070);国家自然科学基金青年科学基金项目(22008114);国家自然科学基金山东联合基金重点项目(U2106228);江苏省自然科学基金青年基金项目(BK20200684);江苏省先进生物制造创新中心资助(XTC2205)
- DOI：10.12211/2096-8280.2022-022
  中图分类号： Q
- 收稿：2022-04-14，
  
  修回：2022-05-25，
  
  纸质出版：2022-12-31
- 稿件说明：
移动端阅览
刘家宇，杨智晗，杨蕾，朱丽英，朱政明，江凌. 合成生物技术驱动酪丁酸梭菌细胞工厂开发的研究进展［J］. 合成生物学， 2022， 3（6）： 1174-1200

LIU Jiayu， YANG Zhihan， YANG Lei， ZHU Liying， ZHU Zhengming， JIANG Ling. Advances in the development of Clostridium tyrobutyricum cell factories driven by synthetic biotechnology［J］. Synthetic Biology Journal， 2022， 3（6）： 1174-1200
刘家宇，杨智晗，杨蕾，朱丽英，朱政明，江凌. 合成生物技术驱动酪丁酸梭菌细胞工厂开发的研究进展［J］. 合成生物学， 2022， 3（6）： 1174-1200 DOI： 10.12211/2096-8280.2022-022.

LIU Jiayu， YANG Zhihan， YANG Lei， ZHU Liying， ZHU Zhengming， JIANG Ling. Advances in the development of Clostridium tyrobutyricum cell factories driven by synthetic biotechnology［J］. Synthetic Biology Journal， 2022， 3（6）： 1174-1200 DOI： 10.12211/2096-8280.2022-022.

摘要

作为一种重要的工业微生物和新型益生菌，酪丁酸梭菌是厌氧条件下代谢多种底物产生丁酸的优势菌株，在其他精细化学品生产和大健康领域亦具有广泛应用。然而，获取生产效率高、鲁棒性强的高版本酪丁酸梭菌细胞工厂，仍然面临着遗传转化效率低、遗传操作工具有限、调控手段单一等诸多挑战。近年来，随着合成生物学的不断发展和酪丁酸梭菌生物信息数据的逐步完善，多种研究策略和技术，包括基因编辑系统等，被用于设计和构筑酪丁酸梭菌底盘细胞高效合成各种精细化学品。本文首先对酪丁酸梭菌独特的生理特性进行了概述。然后，对酪丁酸梭菌底盘细胞改造过程中涉及的系统生物学方法以及遗传操作工具的构建方法与技术进行了总结。同时，探讨了酪丁酸梭菌中多类型代谢调控策略以及群体感应系统的开发及其在合成精细化学品中的应用。最后，从遗传转化效率提升、基因编辑工具拓展、基因回路设计与重构高通量筛选平台建立、一碳气体利用等方面对酪丁酸梭菌底盘细胞的创制进行了展望。

Abstract

As an important industrial microorganism and a novel probiotic

Clostridium tyrobutyricum

is a superior strain for metabolizing various substrates to produce butyric acid under anaerobic condition

presenting a great potential for the valorization of agricultural wastes. Consequently

this bacterium with high yield of butyric acid has also been widely used in other fields

such as fine chemical production and human health. However

there are still many challenges in the construction of highly productive and robust

C. tyrobutyricum

cell factories. For example

the genetic transformation efficiency is rather low

due to the presence of restriction-modification systems. Gene editing tools are less developed

and strain construction suffers from tedious processes and low efficiency. Moreover

genetic modification of

C. tyrobutyricum

is limited to a single mode of metabolic regulation

either knockout or overexpression

which is far behind the conventional model hosts. In recent years

with the continuous rapid development of synthetic biology and the collection of increasing amounts of

C. tyrobutyricum

bioinformatics data

a variety of research strategies and techniques

particularly the gene editing systems

have been employed to design and construct

C. tyrobutyricum

cell factories for efficient production of various fine chemicals. In this paper

we firstly provide an overview of the unique physiological properties of

C. tyrobutyricum

including substrate range

environmental adaptability

butyric acid synthesis pathway

as well as the one-carbon gas fixation and energy metabolism pathways. Subsequently

we summarize the systems biology methods as well as the genetic manipulation tools for the modification of

C. tyrobutyricum

chassis cell

such as biological elements

the conjugation system

and the CRISPR/Cas system. Meanwhile

we discuss the static and dynamic metabolic regulation strategies and two types of quorum sensing systems (

agr-

type and

RRNPP-type) as well as their applications in the synthesis of fine chemicals in

C. tyrobutyricum

. Finally

we prospect the trends for the creation of

C. tyrobutyricum

chassis cell

in terms of enhancing genetic transformation efficiency

expanding gene editing tools

designing and reconstructing gene circuits

establishing high-throughput screening platforms

and utilizing one-carbon gas.

关键词

Keywords

references

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