微生物共培养生产化学品的研究进展

李向来; 申晓林; 王佳; 袁其朋; 孙新晓

doi:10.12211/2096-8280.2020-053

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微生物共培养生产化学品的研究进展

特约评述 | 更新时间：2025-03-20

- 微生物共培养生产化学品的研究进展
- Recent advances in biosynthesis of chemicals by microbial co-culture
- 合成生物学 2021年2卷第6期页码：876-885
- 作者机构：
  
  北京化工大学，化工资源有效利用国家重点实验室，北京 100029
- 作者简介：
  
  [ "李向来（1993—），男，博士研究生。研究方向为代谢工程及合成生物学。E-mail：1003277591@qq.com" ]
  [ "孙新晓（1985—），男，博士，副教授。研究方向为代谢工程及合成生物学。E-mail：sunxx@mail.buct.edu.cn" ]
- 基金信息：
  
  国家重点研发计划项目(2018YFA0901800);北京化工大学双一流项目(XK1802-8;XK1902)
- DOI：10.12211/2096-8280.2020-053
  中图分类号： Q812
- 收稿：2020-04-18，
  
  修回：2021-01-15，
  
  纸质出版：2021-12-31
- 稿件说明：
移动端阅览
李向来，申晓林，王佳，袁其朋，孙新晓. 微生物共培养生产化学品的研究进展［J］. 合成生物学， 2021， 2（6）： 876-885

LI Xianglai， SHEN Xiaolin， WANG Jia， YUAN Qipeng， SUN Xinxiao. Recent advances in biosynthesis of chemicals by microbial co-culture［J］. Synthetic Biology Journal， 2021， 2（6）： 876-885
李向来，申晓林，王佳，袁其朋，孙新晓. 微生物共培养生产化学品的研究进展［J］. 合成生物学， 2021， 2（6）： 876-885 DOI： 10.12211/2096-8280.2020-053.

LI Xianglai， SHEN Xiaolin， WANG Jia， YUAN Qipeng， SUN Xinxiao. Recent advances in biosynthesis of chemicals by microbial co-culture［J］. Synthetic Biology Journal， 2021， 2（6）： 876-885 DOI： 10.12211/2096-8280.2020-053.

摘要

生物合成已成为化学品绿色制造的重要方式。传统上，微生物合成化学品以单菌株培养为主。然而，单培养经常存在引入复杂途径造成沉重代谢负担、细胞微环境无法满足所有酶的功能性表达以及不同途径模块之间相互干扰等问题。借鉴自然界中普遍存在的共生现象，研究者开发了共培养技术，通过在同一体系中培养两种或多种细胞，以充分模拟自然共生环境，实现不同物种之间能量、物质及信号的交流，达到劳动分工以及代谢分区的目的。该技术在减轻宿主代谢负担、提供适宜的酶催化环境以及底物共利用方面表现出突出优势。不过作为一种新兴技术，微生物共培养技术在菌群稳定性、物种兼容性以及菌群比例调控等方面还存在一些挑战。本文列举了近年来微生物共培养划分长途径减轻代谢负担以及利用复杂、混合、非常规底物生产化学品和扩大化学品多样性的成功案例，总结了通过群体感应调控菌群比例以及通过计算机模拟工具预测菌群动态变化的研究进展，并对设计复杂稳定可控的共培养体系在高效生产化学品方面的应用前景和挑战进行了讨论。共培养技术有望成为合成复杂化学品的重要策略，并推动合成生物学的发展。

Abstract

Biosynthesis has become an important way of green manufacturing of chemicals. Traditionally

microbial synthesis of chemicals mainly uses a single strain. However

mono-culture often has the following problems:(1) Introduction of complex pathways causes heavy metabolic burden

(2) the cell microenvironment cannot fulfil the functional expression of all enzymes in the pathways

and (3) the mutual interference between modules of different pathways. Inspired by the natural symbiosis

researchers have developed co-culture technology. By cultivating two or more different cells in the same system

they can fully simulate the natural symbiosis environment

realizing the exchange of energy

materials and signals between different species and achieving the purpose of division of labor and metabolic compartmentation. This technology shows outstanding advantages in reduction of the metabolic burden and provision of suitable environment for different enzymes. Co-culture strategy can also be applied in the aspect of utilizing complex (

e.g.

lignocellulose)

mixed (

e.g.

glucose/xylose/arabinose) or nonconventional (methane

CO and CO

) carbon sources. Synthesis of the target products competes with the nati

ve metabolism for precursors

energy and other resources. Introduction of long pathways in a single strain may cause severe metabolic burden. Splitting and distributing pathways to different cells can alleviate such burden. In addition

each module can be optimized independently

and the balance between the modules can be achieved by adjusting the proportion of strains. Studies have shown that co-culture can significantly affect microbial metabolism and activate silent biosynthetic pathways. In recent years

hundreds of new compounds including polyketones

macrolides and diterpenes have been discovered through co-culture techniques. As an emerging technology

microbial co-culture still has many challenges in the prediction and control of the proportion of different strains. This review lists recent successful cases of microbial co-culture to produce chemicals

summarizes the research progress on regulating the strain proportion through quorum sensing and predicting the dynamic changes through computer simulation tools. Finally

the prospects and challenges in this emerging technology is also discussed.

关键词

Keywords

references

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