Research progress and development of the biosynthesis of 1，4-butanediol by <italic style="font-style: italic">Escherichia coli</italic>

WANG Bowen; QU Mengyuan; LI Hua’nan; CHENG Wanli; LIU Jiashu; JIANG Zhengbing

doi:10.12211/2096-8280.2025-100

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Research progress and development of the biosynthesis of 1，4-butanediol by Escherichia coli

Invited Review | 更新时间：2026-05-22

- Research progress and development of the biosynthesis of 1，4-butanediol by Escherichia coli
- Synthetic Biology Journal Vol. 7, Issue 2, Pages: 357-374(2026)
- 作者机构：
  
  湖北大学生命科学学院，湖北武汉 430062
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2025-100
  CLC： TQ923;Q819
- Received：18 November 2025，
  
  Revised：2026-01-16，
  
  Published：30 April 2026
- 稿件说明：
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王博文，屈梦圆，李华南，程万里，刘家书，江正兵. 大肠杆菌合成生物基1，4-丁二醇的研究进展与发展趋势［J］. 合成生物学， 2026， 7（2）： 357-374

WANG Bowen， QU Mengyuan， LI Hua’nan， CHENG Wanli， LIU Jiashu， JIANG Zhengbing. Research progress and development of the biosynthesis of 1，4-butanediol by Escherichia coli［J］. Synthetic Biology Journal， 2026， 7（2）： 357-374
王博文，屈梦圆，李华南，程万里，刘家书，江正兵. 大肠杆菌合成生物基1，4-丁二醇的研究进展与发展趋势［J］. 合成生物学， 2026， 7（2）： 357-374 DOI： 10.12211/2096-8280.2025-100.

WANG Bowen， QU Mengyuan， LI Hua’nan， CHENG Wanli， LIU Jiashu， JIANG Zhengbing. Research progress and development of the biosynthesis of 1，4-butanediol by Escherichia coli［J］. Synthetic Biology Journal， 2026， 7（2）： 357-374 DOI： 10.12211/2096-8280.2025-100.

摘要

1，4-丁二醇（1，4-BDO）作为一种重要的化工原料，广泛应用于医药、材料、纺织、军工等多个领域。随着全球各国环保政策日趋严格，传统1，4-BDO合成中催化剂昂贵、能耗大等弊端日益凸显。以可再生资源木质纤维素生物质制备可发酵糖，基于合成生物学策略开发低碳、经济、可持续的1，4-BDO生物合成途径显得愈发重要。然而，木质纤维素水解液中多种可发酵糖共存的情况降低了碳源利用效率，木质纤维素预处理后所产生的发酵抑制物同样影响微生物代谢活性。本文综述了以大肠杆菌为底盘细胞，利用不同可发酵糖作为碳源合成1，4-BDO途径的构建思路，总结了提高大肠杆菌耐受多种发酵抑制物的遗传工程策略，探讨了通过构建分工协作、互利共生的多功能模块微生物体系以实现混合糖共利用、原位脱毒以及1，4-BDO高产的可能性。在此基础上，通过计算机辅助1，4-BDO合成途径的挖掘与理性设计、开展基因组尺度代谢网络模型的模拟与优化、对1，4-BDO合成关键酶进行智能设计，在未来将进一步改善1，4-BDO合成效率，为稳定、高产1，4-BDO的大肠杆菌多细胞联合体的构建提供可行性见解与思路。

Abstract

As a key chemical

raw material

4-butanediol (1

4-BDO) is widely utilized in industries

including pharmaceuticals

materials

textiles

and the defense industry sector. With increasingly stringent environmental protection policies worldwide

the shortcomings of conventional 1

4-BDO synthesis

such as the use of costly catalysts and high energy consumption

have become more apparent. Lignocellulosic biomass that is abundant and renewable has great potential in the production of clean fuels and chemicals

but the preparation of fermentable sugars from lignocellulosic biomass is the key step in biorefinery. Based on synthetic biology approaches

the development of a low-carbon

cost-effective

and sustainable route for 1

4-BDO synthesis gains great interest. However

the coexistence of multiple fermentable sugars in lignocellulosic hydrolysates compromises carbon source utilization efficiency. On the other hand

fermentation inhibitors that are generated during the pretreatment process can impair microbial metabolic activity as well

thereby lowering the fermentation efficiency. With

Escherichia coli

as the microbial chassis

this review outlines strategies for constructing 1

4-BDO biosynthesis pathways with different fermentable sugars as carbon sources. Moreover

this review also summarizes genetic engineering approaches to enhance the tolerance of

E. coli

to those fermentation inhibitors

including furfural

5-hydroxymethylfurfural

organic acids

and phenolic substrates. We discuss the possibility of efficient co-utilization of mixed sugars

in situ detoxification

and enhancing the production yield of 1

4-BDO

via

the development of a multifunctional and modular microbial consortium through individual labor and mutualism. Furthermore

by employing computational tools to mine and rationally design 1

4-BDO synthesis pathways

conducting simulations and optimizations based on genome-scale metabolic network models

and applying intelligent design to key enzymes involved in 1

4-BDO

biosynthesis

it is expected that 1

4-BDO synthesis efficiency can be further improved in the future. Overall

this review provides valuable insights and prospects for the construction of robust

high-yield

E. coli

-based microbial consortia for the production of 1

4-BDO.

关键词

Keywords

references

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Research progress and development of the biosynthesis of 1，4-butanediol by Escherichia coli

DOI：10.12211/2096-8280.2025-100

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