微生物合成高级醇的发展趋势与挑战

方馨仪; 孙丽超; 霍毅欣; 王颖; 岳海涛

doi:10.12211/2096-8280.2025-006

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微生物合成高级醇的发展趋势与挑战

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- 微生物合成高级醇的发展趋势与挑战
- Trends and challenges in microbial synthesis of higher alcohols
- 合成生物学 2025年6卷第4期页码：873-898
- 作者机构：
  
  1.新疆大学，新疆乌鲁木齐 830000
  2.北京理工大学生命学院，分子医学与生物诊疗重点实验室，北京 100081
  3.北京理工大学唐山研究院，河北唐山 063000
  4.北京理工大学化学与化工学院，生物化工研究所，医药分子科学与制剂工程工信部重点实验室，北京 100081
- 作者简介：
  
  [ "方馨仪（2000—），女，硕士研究生。研究方向为合成生物学，生物信息，大语言模型。E-mail：107552301711@stu.xju.edu.cn" ]
  [ "王颖（1987—），女，特别研究员，博士生导师。研究方向为合成生物学与代谢工程。E-mail：wy2015@bit.edu.cn" ]
  [ "岳海涛（1980—），男，教授，博士生导师。研究方向为抗逆元件挖掘设计与高版本底盘构建等。E-mail：yuehaitao@tsinghua.org.cn" ]
- 基金信息：
  
  河北省自然科学基金面上项目“基于氨基酸资源分配的代谢调控策略及其在异丁醇生产中的应用”(C2023105022);唐山市科技计划项目(23130228E);新疆维吾尔自治区重点研发任务专项(2023B02034;2023B02034-2);新疆维吾尔自治区青年拔尖人才-基础研究人才(20243122875);国家自然科学基金(U2003305)
- DOI：10.12211/2096-8280.2025-006
  中图分类号： Q816
- 收稿：2025-01-21，
  
  修回：2025-04-18，
  
  纸质出版：2025-08-31
- 稿件说明：
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方馨仪，孙丽超，霍毅欣，王颖，岳海涛. 微生物合成高级醇的发展趋势与挑战［J］. 合成生物学， 2025， 6（4）： 873-898

FANG Xinyi， SUN Lichao， HUO Yixin， WANG Ying， YUE Haitao. Trends and challenges in microbial synthesis of higher alcohols［J］. Synthetic Biology Journal， 2025， 6（4）： 873-898
方馨仪，孙丽超，霍毅欣，王颖，岳海涛. 微生物合成高级醇的发展趋势与挑战［J］. 合成生物学， 2025， 6（4）： 873-898 DOI： 10.12211/2096-8280.2025-006.

FANG Xinyi， SUN Lichao， HUO Yixin， WANG Ying， YUE Haitao. Trends and challenges in microbial synthesis of higher alcohols［J］. Synthetic Biology Journal， 2025， 6（4）： 873-898 DOI： 10.12211/2096-8280.2025-006.

摘要

高级醇是指含有三个或以上碳原子的醇类。传统高级醇的生产主要依赖于石化资源，然而其不可再生性限制了相关产业的发展，因此开发可持续的生物基高级醇生产技术成为研究热点。本文综述了高级醇的市场规模、主要应用领域及其经济价值，并重点分析了异丁醇、1，3-丁二醇和2，3-丁二醇的市场表现。进一步探讨了高级醇的生物合成路径，包括乙酰辅酶A依赖途径、支链氨基酸合成途径和脂肪酸链延长途径，同时总结了代谢工程优化策略，如辅因子平衡调节、竞争途径敲除、酶优化及高产菌株筛选。此外，本文还综述了基于新技术的多维度优化策略，未来有望通过生物传感器、高效基因编辑和计算机辅助代谢工程等技术的结合，进一步优化微生物细胞工厂的设计，有助于提高高级醇的工业化生产效率，为可再生能源和绿色化学工业的发展提供重要支持。

Abstract

Higher alcohols refer to alcohols containing three or more carbon atoms and represent an important class of chemicals widely used in various industries

such as fuels

solvents

coatings

and specialty chemicals. Traditionally

the production of these higher alcohols has depended heavily on petrochemical processes

which not only rely on non-renewable resources but also contribute significantly to environmental pollution. The finite nature of fossil fuels and the associated environmental concerns have prompted researchers to explore alternative

sustainable production methods. Consequently

the development of sustainable bio-based higher alcohol production technologies has emerged as a critical research focus. Recent advances in metabolic engineering and synthetic biology have paved the way for developing engineered microbial strains capable of producing higher alcohols through biological fermentation. By optimizing metabolic pathways

these engineered strains can channel more carbon flux toward the desired alcohol products. In addition

enhancing the tolerance of these strains to high concentrations of the produced alcohols and improving their overall biosynthetic capabilities are key strategies that have been successfully implemented. Such innovations have enabled the production of higher alcohols from renewable feedstocks in a more environmentally friendly and cost-effective manner. Renewable raw materials

such as lignocellulose

waste proteins

waste lipids

and carbon dioxide

provide diverse possibilities for the environmentally friendly and sustainable synthesis of higher alcohols. Lignocellulosic biomass

for instance

is abundant and renewable

making it an attractive alternative to conventional sugars. Waste proteins and lipids

often derived from industrial by-products

provide additional inexpensive substrates that not only help in waste valorization but also reduce the overall production cost. Carbon dioxide

as an abundant greenhouse gas

can be captured and converted into valuable higher alcohols

contributing to carbon sequestration and climate change mitigation. Despite these promising prospects

several challenges remain to be addressed. Issues such as low substrate conversion efficiency

the formation of inhibitory byproducts during fermentation

and high costs associated with downstream separation and purification continue to hinder commercial viability. This review provides a comprehensive overview of the current market size

major applications

and economic value of higher alcohols

with particular emphasis on the market performance of isobutanol

3-butanediol

and 2

3-butanediol. In addition

the review explores the biosynthetic pathways utilized for higher alcohol production

including the acetyl-CoA-dependent pathway

the branched-chain amino acid synthesis pathway

and the fatty acid chain elongation pathway. It also summarizes key metabolic engineering strategies

such as cofactor balancing

competitive pathway elimination

enzyme optimization

and high-yield strain selection. Moreover

the utilization of extremophiles as chassis cells

in combination with next-generation industrial biotechnology (NGIB)

represents a promising new direction for sustainable production. Looking ahead

the integration of biosensors

advanced gene editing technologies

and computer-aided metabolic engineering is expected to further optimize microbial cell factory design

thereby enhancing the industrial production efficiency of higher alcohols and promoting the development of renewable energy and green chemical industries.

关键词

Keywords

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