Trends and challenges in microbial synthesis of higher alcohols

FANG Xinyi; SUN Lichao; HUO Yixin; WANG Ying; YUE Haitao

doi:10.12211/2096-8280.2025-006

您当前的位置：

首页 >

文章列表页 >

Trends and challenges in microbial synthesis of higher alcohols

Invited Review | 更新时间：2025-09-05

- Trends and challenges in microbial synthesis of higher alcohols
- Synthetic Biology Journal Vol. 6, Issue 4, Pages: 873-898(2025)
- 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：
- 基金信息：
- DOI：10.12211/2096-8280.2025-006
  CLC： Q816
- Received：21 January 2025，
  
  Revised：2025-04-18，
  
  Published：31 August 2025
- 稿件说明：
移动端阅览
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

references

PRZYSTAŁOWSKA H , ZEYLAND J , SZYMANOWSKA-POWAŁOWSKA D , et al . 1,3-Propanediol production by new recombinant Escherichia coli containing genes from pathogenic bacteria [J ] . Microbiological Research , 2015 , 171 : 1 - 7 .

ABDERRAZAK H B , FILDIER A , ROMDHANE H B , et al . Synthesis of new poly(ether ketone)s derived from biobased diols [J ] . Macromolecular Chemistry and Physics , 2013 , 214 ( 13 ): 1423 - 1433 .

GARCÍA-HERNÁNDEZ A E , SEGOVIA-HERNÁNDEZ J G , SÁNCHEZ-RAMÍREZ E , et al . Sustainable aviation fuel from butanol: a study in optimizing economic and environmental impact through process intensification [J ] . Chemical Engineering and Processing-Process Intensification , 2024 , 200 : 109769 .

ZHU L F , GUAN X C , XIE N Z , et al . Fermentative production of enantiomerically pure S -1,2-propanediol from glucose by engineered E . coli strain [J ] . Applied Microbiology and Biotechnology , 2016 , 100 ( 3 ): 1241 - 1251 .

SALUSJÄRVI L , HAVUKAINEN S , KOIVISTOINEN O , et al . Biotechnological production of glycolic acid and ethylene glycol: current state and perspectives [J ] . Applied Microbiology and Biotechnology , 2019 , 103 ( 6 ): 2525 - 2535 .

YU C , CAO Y J , ZOU H B , et al . Metabolic engineering of Escherichia coli for biotechnological production of high-value organic acids and alcohols [J ] . Applied Microbiology and Biotechnology , 2011 , 89 ( 3 ): 573 - 583 .

CANN A F , LIAO J C . Production of 2-methyl-1-butanol in engineered Escherichia coli [J ] . Applied Microbiology and Biotechnology , 2008 , 81 ( 1 ): 89 - 98 .

ATSUMI S , HANAI T , LIAO J C . Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels [J ] . Nature , 2008 , 451 ( 7174 ): 86 - 89 .

RADDADI N , CHERIF A , DAFFONCHIO D , et al . Biotechnological applications of extremophiles, extremozymes and extremolytes [J ] . Applied Microbiology and Biotechnology , 2015 , 99 ( 19 ): 7907 - 7913 .

CHEN G Q , JIANG X R . Next generation industrial biotechnology based on extremophilic bacteria [J ] . Current Opinion in Biotechnology , 2018 , 50 : 94 - 100 .

YIN J , CHEN J C , WU Q , et al . Halophiles, coming stars for industrial biotechnology [J ] . Biotechnology Advances , 2015 , 33 ( 7 ): 1433 - 1442 .

Oxo alcohol market size , share & trends analysis report by application , regional outlook , competitive strategies , and segment forecasts , 2019 To 2025 [R/OL ] . 2019[ 2024-12-01 ] . https://www.grandviewresearch.com/industry-analysis/oxo-alcohol-market https://www.grandviewresearch.com/industry-analysis/oxo-alcohol-market .

Tridecyl alcohol market report 2025 (Global edition) [R/OL ] . [ 2024-12-01 ] . https://www.cognitivemarketresearch.com/tridecyl-alcohol-market-report https://www.cognitivemarketresearch.com/tridecyl-alcohol-market-report .

JAISWAL C . Polyols market research report information by product (polyether, polyester) , by application (flexible foam, foamrigid, coatings, adhesives & sealants), and by region (North America, Europe, Asia-Pacific, and rest of the world)-market forecast till 2032[R/OL ] . Market Research Future , 2025 [ 2025-04-18 ] . https://www.marketresearchfuture.com/reports/polyols-market-6114 https://www.marketresearchfuture.com/reports/polyols-market-6114 .

New frontiers: the implication of the revised energy performance of buildings directive in the energy-efficient building market and renewable energy market [EB/OL ] . [ 2025-02-01 ] . https://chinaeucn.com/zh/the-eu-path-to-zero-emission-buildings/ https://chinaeucn.com/zh/the-eu-path-to-zero-emission-buildings/ .

JI X J , HUANG H , OUYANG P K . Microbial 2,3-butanediol production: a state-of-the-art review [J ] . Biotechnology Advances , 2011 , 29 ( 3 ): 351 - 364 .

LIU Z , QIN J Y , GAO C , et al . Production of (2 S ,3 S )-2,3-butanediol and (3 S )-acetoin from glucose using resting cells of Klebsiella pneumonia and Bacillus subtilis [J ] . Bioresource Technology , 2011 , 102 ( 22 ): 10741 - 10744 .

生意社(大宗商品网 . 异丁醇价格-生意社大宗商品数据 [EB/OL ] . [ 2025-02-01 ] . https://www.100ppi.com/mprice/plist-1-1158-1.html https://www.100ppi.com/mprice/plist-1-1158-1.html .

Business Society (Bulk Commodity Network) . Isobutanol price-business society bulk commodity data [EB/OL ] . [ 2025-02-01 ] . https://www.100ppi.com/mprice/plist-1-1158-1.html https://www.100ppi.com/mprice/plist-1-1158-1.html .

ChemAnalyst . Iso Butanol Price Trend and Forecast [EB/OL ] . [ 2025-02-01 ] . https://www.chemanalyst.com/Pricing-data/iso-butanol-22 https://www.chemanalyst.com/Pricing-data/iso-butanol-22 .

QYResearch . 1 , 3 -丁二醇行业剖析:2024年全球市场规模约为2.29亿美元 [EB/OL ] . ( 2025-03-07 )[ 2025-02-01 ] . https://juejin.cn/post/7478872196171677734 https://juejin.cn/post/7478872196171677734 .

QYResearch . Analysis of the 1 , 3 -butanediol industry: the global market size is estimated at USD 229 million in 2024[EB/OL ] . ( 2025-03-07 )[ 2025-02-01 ] . https://juejin.cn/post/7478872196171677734 https://juejin.cn/post/7478872196171677734 .

生意社(大宗商品网 . 1 , 3 -丁二醇价格(生意社大宗商品数据) [EB/OL ] . [ 2025-02-01 ] . https://www.100ppi.com/mprice/plist-1-3361-1.html https://www.100ppi.com/mprice/plist-1-3361-1.html .

Business Society (Bulk Commodity Network) . 1 , 3 -Butanediol price (business society bulk commodity data) [EB/OL ] . [ 2025-02-01 ] . https://www.100ppi.com/mprice/plist-1-3361-1.html https://www.100ppi.com/mprice/plist-1-3361-1.html .

CELIŃSKA E , GRAJEK W . Biotechnological production of 2,3-butanediol—current state and prospects [J ] . Biotechnology Advances , 2009 , 27 ( 6 ): 715 - 725 .

MAINA S , PRABHU A A , VIVEK N , et al . Prospects on bio-based 2,3-butanediol and acetoin production: recent progress and advances [J ] . Biotechnology Advances , 2022 , 54 : 107783 .

JAISWAL C . 2 , 3 -Butanediol market research report: by application (solvents, plasticizers, biodegradable polymers, pharmaceuticals, food additives), by end use industry (automotive, cosmetics, food beverage, pharmaceuticals, polymer), by product form (liquid, solid, gas), by production method (fermentation, chemical synthesis, biochemical process) and by regional (North America, Europe, South America, Asia Pacific, Middle East and Africa) - forecast to 2034 [R/OL ] . Market Research Future , 2025[ 2025-04-18 ] . https://www.marketresearchfuture.com/reports/2-3-butanediol-market-34339 https://www.marketresearchfuture.com/reports/2-3-butanediol-market-34339 .

习近平在第七十五届联合国大会一般性辩论上发表重要讲话 [EB/OL ] . ( 2020-09-22 )[ 2025-02-01 ] . https://www.xinhuanet.com//politics/2020-09/22/c_1126527647.htm https://www.xinhuanet.com//politics/2020-09/22/c_1126527647.htm .

Xi Jinping delivered an important speech at the general debate of the 75th session of the United Nations general assembly [EB/OL ] . ( 2020-09-22 )[ 2025-02-01 ] . https://www.xinhuanet.com//politics/2020-09/22/c_1126527647.htm https://www.xinhuanet.com//politics/2020-09/22/c_1126527647.htm .

LI C Z , ZHAO X C , WANG A Q , et al . Catalytic transformation of lignin for the production of chemicals and fuels [J ] . Chemical Reviews , 2015 , 115 ( 21 ): 11559 - 11624 .

ALONSO D M , WETTSTEIN S G , DUMESIC J A . Bimetallic catalysts for upgrading of biomass to fuels and chemicals [J ] . Chemical Society Reviews , 2012 , 41 ( 24 ): 8075 - 8098 .

KUMAR R , SINGH S , SINGH O V . Bioconversion of lignocellulosic biomass: biochemical and molecular perspectives [J ] . Journal of Industrial Microbiology & Biotechnology , 2008 , 35 ( 5 ): 377 - 391 .

DENG W P , FENG Y C , FU J , et al . Catalytic conversion of lignocellulosic biomass into chemicals and fuels [J ] . Green Energy & Environment , 2023 , 8 ( 1 ): 10 - 114 .

NDUKWE N A , IDIKA D I , OKIEI W O . Influence of cellulose-cellulase enzyme digestibility in the production of glucose from lignocellulosic biomass waste [J ] . IOP Conference Series: Earth and Environmental Science , 2024 , 1322 ( 1 ): 012005 .

DEMEKE M M , ECHEMENDIA D , BELO E , et al . Enhancing xylose-fermentation capacity of engineered Saccharomyces cerevisiae by multistep evolutionary engineering in inhibitor-rich lignocellulose hydrolysate [J ] . FEMS Yeast Research , 2024 , 24 : foae013 .

KUSUMOTO S , HIGASHI T , MATSUMOTO Y , et al . Hydrogenative degradation of PEG-functionalized lignin [J ] . Polymer Journal , 2024 , 56 ( 4 ): 353 - 357 .

MA C Y , LUO X T , XU L H , et al . Structural elucidation and targeted valorization of untractable lignin from pre-hydrolysis liquor of xylose production via a simple and robust separation approach [J ] . International Journal of Biological Macromolecules , 2023 , 253 : 127029 .

ZHANG S Z , DUAN Y , TENG C C , et al . Fast and selective degradation of biomass for xylose, glucose and lignin under mild conditions [J ] . Molecules , 2023 , 28 ( 8 ): 3306 .

国家统计局 . 2023年国民经济回升向好高质量发展扎实推进 [EB/OL ] .( 2024-01-17 )[ 2025-02-01 ] . https://www.stats.gov.cn/sj/xwfbh/fbhwd/202401/t20240117_1946624.html https://www.stats.gov.cn/sj/xwfbh/fbhwd/202401/t20240117_1946624.html .

National Bureau of Statistics . The national economy improved in 2023 with solid progress in high-quality development [EB/OL ] .( 2024-01-17 )[ 2025-02-01 ] . https://www.stats.gov.cn/sj/xwfbh/fbhwd/202401/t20240117_1946624.html https://www.stats.gov.cn/sj/xwfbh/fbhwd/202401/t20240117_1946624.html .

ABDELGHANY A M , ZHANG S R , AZAM M , et al . Natural variation in fatty acid composition of diverse world soybean germplasms grown in China [J ] . Agronomy , 2020 , 10 ( 1 ): 24 .

ZHANG H L , GAO J R , ZHAO Z D , et al . Esterification of fatty acids from waste cooking oil to biodiesel over a sulfonated resin/PVA composite [J ] . Catalysis Science & Technology , 2016 , 6 ( 14 ): 5590 - 5598 .

GANESH I , RAVIKUMAR S , HONG S H . Metabolically engineered Escherichia coli as a tool for the production of bioenergy and biochemicals from glycerol [J ] . Biotechnology and Bioprocess Engineering , 2012 , 17 ( 4 ): 671 - 678 .

KRISHNAN A , MCNEIL B A , STUART D T . Biosynthesis of fatty alcohols in engineered microbial cell factories: advances and limitations [J ] . Frontiers in Bioengineering and Biotechnology , 2020 , 8 : 610936 .

CERÓN FERRUSCA M , ROMERO R , MARTÍNEZ S L , et al . Biodiesel production from waste cooking oil: a perspective on catalytic processes [J ] . Processes , 2023 , 11 ( 7 ): 1952 .

JATOI A S , ALI SHAH A , AHMED J , et al . Hydrothermal liquefaction of lignocellulosic and protein-containing biomass: a comprehensive review [J ] . Catalysts , 2022 , 12 ( 12 ): 1621 .

ÄYRÄPÄÄ T . Formation of higher alcohols from amino acids derived from yeast proteins [J ] . Journal of the Institute of Brewing , 1967 , 73 ( 1 ): 30 - 33 .

EL-DALATONY M M , SAHA S , GOVINDWAR S P , et al . Biological conversion of amino acids to higher alcohols [J ] . Trends in Biotechnology , 2019 , 37 ( 8 ): 855 - 869 .

何新媛 , 刘杨 , 曾祥荷 , 等 . 基于生物信息学的蛋白质功能预测方法研究进展 [J ] . 生物工程学报 , 2024 , 40 ( 7 ): 2087 - 2099 .

HE X Y , LIU Y , ZENG X H , et al . Advances in bioinformatics-based protein function prediction [J ] . Chinese Journal of Biotechnology , 2024 , 40 ( 7 ): 2087 - 2099 .

MU D D , LI P L , MA T G , et al . Advances in the understanding of the production, modification and applications of xylanases in the food industry [J ] . Enzyme and Microbial Technology , 2024 , 179 : 110473 .

PARK M K , SHIN D M , CHOI Y S . Comparison of volatile compound profiles derived from various livestock protein alternatives including edible-insect, and plant-based proteins [J ] . Food Chemistry: X , 2024 , 23 : 101570 .

CO 2 ·Earth . Daily CO 2 [EB/OL ] . [ 2025-02-01 ] . https://www.co2.earth/daily-co2 https://www.co2.earth/daily-co2 .

IEA . CO 2 emissions in 2023 [R/OL ] . Paris : IEA , 2024 [ 2025-02-01 ] . https://www.iea.org/reports/co2-emissions-in-2023 https://www.iea.org/reports/co2-emissions-in-2023 .

IEA . CO 2 capture and utilisation [EB/OL ] . [ 2025-04-18 ] . https://www.iea.org/energy-system/carbon-capture-utilisation-and-storage/co2-capture-and-utilisation https://www.iea.org/energy-system/carbon-capture-utilisation-and-storage/co2-capture-and-utilisation .

Research and markets . The global market for carbon dioxide(CO 2 ) [R ] . 2023 .

IEA . Putting CO 2 to use [R/OL ] . Paris : IEA , 2019 [ 2025-02-01 ] . https://www.iea.org/reports/putting-co2-to-use https://www.iea.org/reports/putting-co2-to-use .

Hydrocarbon Processing . World’s largest CO 2 -to-methanol plant starts production [EB/OL ] . ( 2022-10-28 )[ 2025-02-01 ] . https://www.hydrocarbonprocessing.com/news/2022/10/worlds-largest-co2-to-methanol-plant-starts-production https://www.hydrocarbonprocessing.com/news/2022/10/worlds-largest-co2-to-methanol-plant-starts-production .

BERGGREN M . Global methanol outlook 2023: growth and decarbonization [R/OL ] . ( 2023-06-07 )[ 2024-12-01 ] . https://cdnpetrochemicalsummit.com/wp-content/uploads/2023/06/3-Mark-Berggren-for-CPS-2023-Global-Methanol.pdf https://cdnpetrochemicalsummit.com/wp-content/uploads/2023/06/3-Mark-Berggren-for-CPS-2023-Global-Methanol.pdf .

PANICH J , TOPPARI E , TEJEDOR-SANZ S , et al . Functional plasticity of HCO 3 - uptake and CO 2 fixation in Cupriavidus necator H16 [EB/OL ] . bioRxiv , 2024 : 2024 .2005. 2007 .593039. ( 2024-05-07 )[ 2024-12-01 ] . https://doi.org/10.1101/2024.05. 07.593039 https://doi.org/10.1101/2024.05.07.593039 .

MACLEAN M R , CLARK D A , LAIGLE L , et al . Carbon dioxide uptake and fixation by ferrous iron-oxidizing acidophilic bacteria [J ] . Minerals Engineering , 2024 , 206 : 108532 .

WANNICKE N , STÜEKEN E E , BAUERSACHS T , et al . Exploring the influence of atmospheric CO 2 and O 2 levels on the utility of nitrogen isotopes as proxy for biological N2 fixation[EB/OL ] . bioRxiv , 2024 : 2024 .2003. 2028 .587259. ( 2024-04-02 )[ 2024-12-01 ] . https://doi.org/10.1101/2024.03. 28.587259 https://doi.org/10.1101/2024.03.28.587259 .

CHEN H C , WANG D Q , WANG C C , et al . Lower micromolar activity of the antifungal imidazoles on the bacterial-type bifunctional aldehyde/alcohol dehydrogenase (AdhE) in Cryptosporidium parvum and in vitro efficacy against the zoonotic parasite [J ] . International Journal for Parasitology Drugs and Drug Resistance , 2024 , 25 : 100551 .

BROSSIER C , JARDOU M , JANASZKIEWICZ A , et al . Gut microbiota biotransformation of drug glucuronides leading to gastrointestinal toxicity: Therapeutic potential of bacterial β-glucuronidase inhibition in mycophenolate-induced enteropathy [J ] . Life Sciences , 2024 , 351 : 122792 .

ATSUMI S , CANN A F , CONNOR M R , et al . Metabolic engineering of Escherichia coli for 1-butanol production [J ] . Metabolic Engineering , 2008 , 10 ( 6 ): 305 - 311 .

MAINGUET S E , LIAO J C . Bioengineering of microorganisms for C 3 to C 5 alcohols production [J ] . Biotechnology Journal , 2010 , 5 ( 12 ): 1297 - 1308 .

SCHADEWEG V , BOLES E . n -Butanol production in Saccharomyces cerevisiae is limited by the availability of coenzyme A and cytosolic acetyl-CoA [J ] . Biotechnology for Biofuels , 2016 , 9 : 44 .

KURIAN J V . A new polymer platform for the future—sorona ® from corn derived 1,3-propanediol [J ] . Journal of Polymers and the Environment , 2005 , 13 ( 2 ): 159 - 167 .

LI Z H , WU Z Y , CEN X C , et al . Efficient production of 1,3-propanediol from diverse carbohydrates via a non-natural pathway using 3-hydroxypropionic acid as an intermediate [J ] . ACS Synthetic Biology , 2021 , 10 ( 3 ): 478 - 486 .

LEE Y G , SEO J H . Production of 2,3-butanediol from glucose and cassava hydrolysates by metabolically engineered industrial polyploid Saccharomyces cerevisiae [J ] . Biotechnology for Biofuels , 2019 , 12 ( 1 ): 204 .

KOU M Y , CUI Z Z , FU J , et al . Metabolic engineering of Corynebacterium glutamicum for efficient production of optically pure (2 R ,3 R )-2,3-butanediol [J ] . Microbial Cell Factories , 2022 , 21 ( 1 ): 150 .

YIM H , HASELBECK R , NIU W , et al . Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol [J ] . Nature Chemical Biology , 2011 , 7 ( 7 ): 445 - 452 .

CEN X C , LIU Y J , ZHU F H , et al . Metabolic engineering of Escherichia coli for high production of 1,5-pentanediol via a cadaverine-derived pathway [J ] . Metabolic Engineering , 2022 , 74 : 168 - 177 .

ATSUMI S , LIAO J C . Directed evolution of Methanococcus jannaschii citramalate synthase for biosynthesis of 1-propanol and 1-butanol by Escherichia coli [J ] . Applied and Environmental Microbiology , 2008 , 74 ( 24 ): 7802 - 7808 .

CHOI Y J , PARK J H , KIM T Y , et al . Metabolic engineering of Escherichia coli for the production of 1-propanol [J ] . Metabolic Engineering , 2012 , 14 ( 5 ): 477 - 486 .

INOKUMA K , LIAO J C , OKAMOTO M , et al . Improvement of isopropanol production by metabolically engineered Escherichia coli using gas stripping [J ] . Journal of Bioscience and Bioengineering , 2010 , 110 ( 6 ): 696 - 701 .

SOMA Y , INOKUMA K , TANAKA T , et al . Direct isopropanol production from cellobiose by engineered Escherichia coli using a synthetic pathway and a cell surface display system [J ] . Journal of Bioscience and Bioengineering , 2012 , 114 ( 1 ): 80 - 85 .

JOJIMA T , INUI M , YUKAWA H . Production of isopropanol by metabolically engineered Escherichia coli [J ] . Applied Microbiology and Biotechnology , 2008 , 77 ( 6 ): 1219 - 1224 .

LEE J M , JANG Y S , CHOI S J , et al . Metabolic engineering of Clostridium acetobutylicum ATCC 824 for isopropanol-butanol-ethanol fermentation [J ] . Applied and Environmental Microbiology , 2012 , 78 ( 5 ): 1416 - 1423 .

DUSSÉAUX S , CROUX C , SOUCAILLE P , et al . Metabolic engineering of Clostridium acetobutylicum ATCC 824 for the high-yield production of a biofuel composed of an isopropanol/butanol/ethanol mixture [J ] . Metabolic Engineering , 2013 , 18 : 1 - 8 .

LAN E I , LIAO J C . Metabolic engineering of cyanobacteria for 1-butanol production from carbon dioxide [J ] . Metabolic Engineering , 2011 , 13 ( 4 ): 353 - 363 .

LAN E I , LIAO J C . ATP drives direct photosynthetic production of 1-butanol in cyanobacteria [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2012 , 109 ( 16 ): 6018 - 6023 .

JANG Y S , LEE J Y , LEE J , et al . Enhanced butanol production obtained by reinforcing the direct butanol-forming route in Clostridium acetobutylicum [J ] . mBio , 2012 , 3 ( 5 ): e00314-12 .

YU M R , DU Y M , JIANG W Y , et al . Effects of different replicons in conjugative plasmids on transformation efficiency, plasmid stability, gene expression and n -butanol biosynthesis in Clostridium tyrobutyricum [J ] . Applied Microbiology and Biotechnology , 2012 , 93 ( 2 ): 881 - 889 .

STEEN E J , CHAN R , PRASAD N , et al . Metabolic engineering of Saccharomyces cerevisiae for the production of n-butanol [J ] . Microbial Cell Factories , 2008 , 7 : 36 .

NIELSEN D R , LEONARD E , YOON S H , et al . Engineering alternative butanol production platforms in heterologous bacteria [J ] . Metabolic Engineering , 2009 , 11 ( 4-5 ): 262 - 273 .

BEREZINA O V , ZAKHAROVA N V , BRANDT A , et al . Reconstructing the clostridial n -butanol metabolic pathway in Lactobacillus brevis [J ] . Applied Microbiology and Biotechnology , 2010 , 87 ( 2 ): 635 - 646 .

KÖPKE M , HELD C , HUJER S , et al . Clostridium ljungdahlii represents a microbial production platform based on syngas [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2010 , 107 ( 29 ): 13087 - 13092 .

SHEN C R , LAN E I , DEKISHIMA Y , et al . Driving forces enable high-titer anaerobic 1-butanol synthesis in Escherichia coli [J ] . Applied and Environmental Microbiology , 2011 , 77 ( 9 ): 2905 - 2915 .

YU H , WANG N , HUO W B , et al . Establishment of BmoR-based biosensor to screen isobutanol overproducer [J ] . Microbial Cell Factories , 2019 , 18 ( 1 ): 30 .

ATSUMI S , HIGASHIDE W , LIAO J C . Direct photosynthetic recycling of carbon dioxide to isobutyraldehyde [J ] . Nature Biotechnology , 2009 , 27 ( 12 ): 1177 - 1180 .

SU H F , LIN J F , WANG G W . Metabolic engineering of Corynebacterium crenatium for enhancing production of higher alcohols [J ] . Scientific Reports , 2016 , 6 : 39543 .

BOOCK J T , FREEDMAN A J E , TOMPSETT G A , et al . Engineered microbial biofuel production and recovery under supercritical carbon dioxide [J ] . Nature Communications , 2019 , 10 : 587 .

LI S S , JIA X Q , WEN J P . Improved 2-methyl-1-propanol production in an engineered Bacillus subtilis by constructing inducible pathways [J ] . Biotechnology Letters , 2012 , 34 ( 12 ): 2253 - 2258 .

HIGASHIDE W , LI Y C , YANG Y F , et al . Metabolic engineering of Clostridium cellulolyticum for production of isobutanol from cellulose [J ] . Applied and Environmental Microbiology , 2011 , 77 ( 8 ): 2727 - 2733 .

BLOMBACH B , RIESTER T , WIESCHALKA S , et al . Corynebacterium glutamicum tailored for efficient isobutanol production [J ] . Applied and Environmental Microbiology , 2011 , 77 ( 10 ): 3300 - 3310 .

LI H , OPGENORTH P H , WERNICK D G , et al . Integrated electromicrobial conversion of CO 2 to higher alcohols [J ] . Science , 2012 , 335 ( 6076 ): 1596 .

LU J N , BRIGHAM C J , GAI C S , et al . Studies on the production of branched-chain alcohols in engineered Ralstonia eutropha [J ] . Applied Microbiology and Biotechnology , 2012 , 96 ( 1 ): 283 - 297 .

MATSUDA F , ISHII J , KONDO T , et al . Increased isobutanol production in Saccharomyces cerevisiae by eliminating competing pathways and resolving cofactor imbalance [J ] . Microbial Cell Factories , 2013 , 12 : 119 .

QIU M Y , SHEN W , YAN X Y , et al . Metabolic engineering of Zymomonas mobilis for anaerobic isobutanol production [J ] . Biotechnology for Biofuels , 2020 , 13 : 15 .

LIN P P , MI L , MORIOKA A H , et al . Consolidated bioprocessing of cellulose to isobutanol using Clostridium thermocellum [J ] . Metabolic Engineering , 2015 , 31 : 44 - 52 .

HASEGAWA S , JOJIMA T , SUDA M , et al . Isobutanol production in Corynebacterium glutamicum : suppressed succinate by-production by pckA inactivation and enhanced productivity via the Entner-Doudoroff pathway [J ] . Metabolic Engineering , 2020 , 59 : 24 - 35 .

RUSSMAYER H , MARX H , SAUER M . Microbial 2-butanol production with Lactobacillus diolivorans [J ] . Biotechnology for Biofuels , 2019 , 12 : 262 .

CHEN Z , WU Y , HUANG J H , et al . Metabolic engineering of Klebsiella pneumoniae for the de novo production of 2-butanol as a potential biofuel [J ] . Bioresource Technology , 2015 , 197 : 260 - 265 .

GHIACI P , LAMEIRAS F , NORBECK J , et al . Production of 2-butanol through meso -2,3-butanediol consumption in lactic acid bacteria [J ] . FEMS Microbiology Letters , 2014 , 360 ( 1 ): 70 - 75 .

GHIACI P , NORBECK J , LARSSON C . 2-Butanol and butanone production in Saccharomyces cerevisiae through combination of a B 12 dependent dehydratase and a secondary alcohol dehydrogenase using a TEV-based expression system [J ] . PLoS One , 2014 , 9 ( 7 ): e102774 .

SPERANZA G , CORTI S , FONTANA G , et al . Conversion of meso- 2,3-butanediol into 2-butanol by Lactobacilli . Stereochemical and enzymatic aspects [J ] . Journal of agricultural and food chemistry , 1997 , 45 ( 9 ): 3476 - 3480 .

SU H F , LIN J F , WANG Y H , et al . Engineering Brevibacterium flavum for the production of renewable bioenergy: C 4 –C 5 advanced alcohols [J ] . Biotechnology and Bioengineering , 2017 , 114 ( 9 ): 1946 - 1958 .

SU H F , CHEN H , LIN J F . Enriching the production of 2-methyl-1-butanol in fermentation process using Corynebacterium crenatum [J ] . Current Microbiology , 2020 , 77 ( 8 ): 1699 - 1706 .

CONNOR M R , CANN A F , LIAO J C . 3-Methyl-1-butanol production in Escherichia coli : random mutagenesis and two-phase fermentation [J ] . Applied Microbiology and Biotechnology , 2010 , 86 ( 4 ): 1155 - 1164 .

RAO B , ZHANG L Y , SUN J A , et al . Characterization and regulation of the 2,3-butanediol pathway in Serratia marcescens [J ] . Applied Microbiology and Biotechnology , 2012 , 93 ( 5 ): 2147 - 2159 .

ZHANG L Y , SUN J A , HAO Y L , et al . Microbial production of 2,3-butanediol by a surfactant (serrawettin)-deficient mutant of Serratia marcescens H30 [J ] . Journal of Industrial Microbiology & Biotechnology , 2010 , 37 ( 8 ): 857 - 862 .

YANG S H , MOHAGHEGHI A , FRANDEN M A , et al . Metabolic engineering of Zymomonas mobilis for 2,3-butanediol production from lignocellulosic biomass sugars [J ] . Biotechnology for Biofuels , 2016 , 9 ( 1 ): 189 .

UI S , OKAJIMA Y , MIMURA A , et al . Molecular generation of an Escherichia coli strain producing only the meso -isomer of 2,3-butanediol [J ] . Journal of Fermentation and Bioengineering , 1997 , 84 ( 3 ): 185 - 189 .

YAN Y J , LEE C C , LIAO J C . Enantioselective synthesis of pure ( R , R )-2,3-butanediol in Escherichia coli with stereospecific secondary alcohol dehydrogenases [J ] . Organic & Biomolecular Chemistry , 2009 , 7 ( 19 ): 3914 - 3917 .

CHU H P , XIN B , LIU P H , et al . Metabolic engineering of Escherichia coli for production of (2 S ,3 S )-butane-2,3-diol from glucose [J ] . Biotechnology for Biofuels , 2015 , 8 : 143 .

RESHAMWALA S M S , DEB S S , LALI A M . A shortened, two-enzyme pathway for 2,3-butanediol production in Escherichia coli [J ] . Journal of Industrial Microbiology & Biotechnology , 2017 , 44 ( 9 ): 1273 - 1277 .

TONG Y J , JI X J , SHEN M Q , et al . Constructing a synthetic constitutive metabolic pathway in Escherichia coli for ( R , R )-2,3-butanediol production [J ] . Applied Microbiology and Biotechnology , 2016 , 100 ( 2 ): 637 - 647 .

HWANG H J , LEE S Y , LEE P C . Engineering and application of synthetic nar promoter for fine-tuning the expression of metabolic pathway genes in Escherichia coli [J ] . Biotechnology for Biofuels , 2018 , 11 : 103 .

ERIAN A M , GIBISCH M , PFLÜGL S . Engineered E . coli W enables efficient 2,3-butanediol production from glucose and sugar beet molasses using defined minimal medium as economic basis [J ] . Microbial Cell Factories , 2018 , 17 ( 1 ): 190 .

LI Z J , JIAN J , WEI X X , et al . Microbial production of meso -2,3-butanediol by metabolically engineered Escherichia coli under low oxygen condition [J ] . Applied Microbiology and Biotechnology , 2010 , 87 ( 6 ): 2001 - 2009 .

WANG Y , LI L X , MA C Q , et al . Engineering of cofactor regeneration enhances (2 S ,3 S )-2,3-butanediol production from diacetyl [J ] . Scientific Reports , 2013 , 3 : 2643 .

UI S , TAKUSAGAWA Y , SATO T , et al . Production of L-2,3-butanediol by a new pathway constructed in Escherichia coli [J ] . Letters in Applied Microbiology , 2004 , 39 ( 6 ): 533 - 537 .

MAZUMDAR S , LEE J , OH M K . Microbial production of 2,3-butanediol from seaweed hydrolysate using metabolically engineered Escherichia coli [J ] . Bioresource Technology , 2013 , 136 : 329 - 336 .

SHIN H D , YOON S H , WU J R , et al . High-yield production of meso -2,3-butanediol from cellodextrin by engineered E . coli biocatalysts [J ] . Bioresource Technology , 2012 , 118 : 367 - 373 .

JAIN R , SUN X X , YUAN Q P , et al . Systematically engineering Escherichia coli for enhanced production of 1,2-propanediol and 1-propanol [J ] . ACS Synthetic Biology , 2015 , 4 ( 6 ): 746 - 756 .

LIANG Q F , ZHANG H J , LI S N , et al . Construction of stress-induced metabolic pathway from glucose to 1,3-propanediol in Escherichia coli [J ] . Applied Microbiology and Biotechnology , 2011 , 89 ( 1 ): 57 - 62 .

YANG B , LIANG S X , LIU H H , et al . Metabolic engineering of Escherichia coli for 1,3-propanediol biosynthesis from glycerol [J ] . Bioresource Technology , 2018 , 267 : 599 - 607 .

TANG X M , TAN Y S , ZHU H , et al . Microbial conversion of glycerol to 1,3-propanediol by an engineered strain of Escherichia coli [J ] . Applied and Environmental Microbiology , 2009 , 75 ( 6 ): 1628 - 1634 .

YUN J H , ZABED H M , ZHANG Y F , et al . Co-fermentation of glycerol and glucose by a co-culture system of engineered Escherichia coli strains for 1,3-propanediol production without vitamin B 12 supplementation [J ] . Bioresource Technology , 2021 , 319 : 124218 .

LI Z H , DONG Y F , LIU Y , et al . Systems metabolic engineering of Corynebacterium glutamicum for high-level production of 1,3-propanediol from glucose and xylose [J ] . Metabolic Engineering , 2022 , 70 : 79 - 88 .

ZHANG Y , SUN Q , LIU Y , et al . Development of a plasmid stabilization system in Vibrio natriegens for the high production of 1,3-propanediol and 3-hydroxypropionate [J ] . Bioresources and Bioprocessing , 2021 , 8 ( 1 ): 125 .

ZHANG Y J , MA C W , DISCHERT W , et al . Engineering of phosphoserine aminotransferase increases the conversion of L-homoserine to 4-hydroxy-2-ketobutyrate in a glycerol-independent pathway of 1,3-propanediol production from glucose [J ] . Biotechnology Journal , 2019 , 14 ( 9 ): 1900003 .

LI M D , ZHANG Y , LI J C , et al . Biosynthesis of 1,3-propanediol via a new pathway from glucose in Escherichia coli [J ] . ACS Synthetic Biology , 2023 , 12 ( 7 ): 2083 - 2093 .

GUO J , CAO Y J , LIU H , et al . Improving the production of isoprene and 1,3-propanediol by metabolically engineered Escherichia coli through recycling redox cofactor between the dual pathways [J ] . Applied Microbiology and Biotechnology , 2019 , 103 ( 6 ): 2597 - 2608 .

KATAOKA N , VANGNAI A S , UEDA H , et al . Enhancement of ( R )-1,3-butanediol production by engineered Escherichia coli using a bioreactor system with strict regulation of overall oxygen transfer coefficient and pH [J ] . Bioscience, Biotechnology, and Biochemistry , 2014 , 78 ( 4 ): 695 - 700 .

LIU Y , CEN X C , LIU D H , et al . Metabolic engineering of Escherichia coli for high-yield production of ( R )-1,3-butanediol [J ] . ACS Synthetic Biology , 2021 , 10 ( 8 ): 1946 - 1955 .

WANG J , ZHANG R H , ZHANG J L , et al . Tunable hybrid carbon metabolism coordination for the carbon-efficient biosynthesis of 1,3-butanediol in Escherichia coli [J ] . Green Chemistry , 2021 , 23 ( 21 ): 8694 - 8706 .

ISLAM T , NGUYEN-VO T P , GAUR V K , et al . Metabolic engineering of Escherichia coli for biological production of 1,3-butanediol [J ] . Bioresource Technology , 2023 , 376 : 128911 .

ISLAM T , NGUYEN-VO T P , CHO S , et al . Metabolic engineering of Escherichia coli for enhanced production of 1,3-butanediol from glucose [J ] . Bioresource Technology , 2023 , 389 : 129814 .

KIM T H , FLICK R , BRUNZELLE J , et al . Novel aldo-keto reductases for the biocatalytic conversion of 3-hydroxybutanal to 1,3-butanediol: structural and biochemical studies [J ] . Applied and Environmental Microbiology , 2017 , 83 ( 7 ): e03172-16 .

WU M Y , SUNG L Y , LI H , et al . Combining CRISPR and CRISPRi systems for metabolic engineering of E . coli and 1,4-BDO biosynthesis [J ] . ACS Synthetic Biology , 2017 , 6 ( 12 ): 2350 - 2361 .

TAI Y S , XIONG M Y , JAMBUNATHAN P , et al . Engineering nonphosphorylative metabolism to generate lignocellulose-derived products [J ] . Nature Chemical Biology , 2016 , 12 ( 4 ): 247 - 253 .

BURGARD A , BURK M J , OSTERHOUT R , et al . Development of a commercial scale process for production of 1,4-butanediol from sugar [J ] . Current Opinion in Biotechnology , 2016 , 42 : 118 - 125 .

WANG J , LI C Y , ZOU Y S , et al . Bacterial synthesis of C 3 -C 5 diols via extending amino acid catabolism [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2020 , 117 ( 32 ): 19159 - 19167 .

ALTARAS N E , CAMERON D C . Metabolic engineering of a 1,2-propanediol pathway in Escherichia coli [J ] . Applied and Environmental Microbiology , 1999 , 65 ( 3 ): 1180 - 1185 .

ALTARAS N E , CAMERON D C . Enhanced production of ( R )-1,2-propanediol by metabolically engineered Escherichia coli [J ] . Biotechnology Progress , 2000 , 16 ( 6 ): 940 - 946 .

NIU W , GUO J T . Stereospecific microbial conversion of lactic acid into 1,2-propanediol [J ] . ACS Synthetic Biology , 2015 , 4 ( 4 ): 378 - 382 .

CLOMBURG J M , GONZALEZ R . Metabolic engineering of Escherichia coli for the production of 1,2-propanediol from glycerol [J ] . Biotechnology and Bioengineering , 2011 , 108 ( 4 ): 867 - 879 .

JING P Y , CAO X , LU X Y , et al . Modification of an engineered Escherichia coli by a combined strategy of deleting branch pathway, fine-tuning xylose isomerase expression, and substituting decarboxylase to improve 1,2,4-butanetriol production [J ] . Journal of Bioscience and Bioengineering , 2018 , 126 ( 5 ): 547 - 552 .

ZHANG N N , WANG J B , ZHANG Y , et al . Metabolic pathway optimization for biosynthesis of 1,2,4-butanetriol from xylose by engineered Escherichia coli [J ] . Enzyme and Microbial Technology , 2016 , 93-94 : 51 - 58 .

孙雷 , 杨帆 , 朱泰承 , 等 . 大肠杆菌合成1,2,4-丁三醇的途径优化 [J ] . 生物工程学报 , 2016 , 32 ( 1 ): 51 - 63 .

SUN L , YANG F , ZHU T C , et al . Optimization of 1,2,4-butanetriol synthetic pathway in Escherichia coli [J ] . Chinese Journal of Biotechnology , 2016 , 32 ( 1 ): 51 - 63 .

WANG X , XU N N , HU S W , et al . D-1,2,4-butanetriol production from renewable biomass with optimization of synthetic pathway in engineered Escherichia coli [J ] . Bioresource Technology , 2018 , 250 : 406 - 412 .

FENG X J , GAO W J , ZHOU Y F , et al . Coupled biosynthesis and esterification of 1,2,4-butanetriol to simplify its separation from fermentation broth [J ] . Engineering in Life Sciences , 2019 , 19 ( 6 ): 444 - 451 .

BAMBA T , YUKAWA T , GUIRIMAND G , et al . Production of 1,2,4-butanetriol from xylose by Saccharomyces cerevisiae through Fe metabolic engineering [J ] . Metabolic Engineering , 2019 , 56 : 17 - 27 .

WANG G L , WANG M Y , YANG J C , et al . De novo synthesis of 2-phenylethanol from glucose by metabolically engineered Escherichia coli [J ] . Journal of Industrial Microbiology and Biotechnology , 2022 , 49 ( 6 ): kuac026 .

马晓焉 , 王雪芹 , 马炼杰 , 等 . 高级醇的微生物绿色制造 [J ] . 生物工程学报 , 2021 , 37 ( 5 ): 1721 - 1736 .

MA X Y , WANG X Q , MA L J , et al . Microbial green manufacturing of higher alcohols [J ] . Chinese Journal of Biotechnology , 2021 , 37 ( 5 ): 1721 - 1736 .

CHEN R B , YANG S , ZHANG L , et al . Advanced strategies for production of natural products in yeast [J ] . iScience , 2020 , 23 ( 3 ): 100879 .

WANG P C , YANG X W , LIN B X , et al . Cofactor self-sufficient whole-cell biocatalysts for the production of 2-phenylethanol [J ] . Metabolic Engineering , 2017 , 44 : 143 - 149 .

LIU H Y , WU X X , MA H , et al . High-level production of hydroxytyrosol in engineered Saccharomyces cerevisiae [J ] . ACS Synthetic Biology , 2022 , 11 ( 11 ): 3706 - 3713 .

XIAO F , LI D F , PAN Y J , et al . Establishing Komagataella phaffii as a cell factory for efficient production of cholesterol sulfate [J ] . ACS Sustainable Chemistry & Engineering , 2025 , 13 ( 1 ): 174 - 186 .

ASPACIO D , ZHANG Y L , CUI Y T , et al . Shifting redox reaction equilibria on demand using an orthogonal redox cofactor [J ] . Nature Chemical Biology , 2024 , 20 ( 11 ): 1535 - 1546 .

WANG Y X , WAN Z J , ZHU Y T , et al . Enhanced 1,3-propanediol production with high yield from glycerol through a novel Klebsiella - Shewanella co-culture [J ] . Biotechnology for Biofuels and Bioproducts , 2023 , 16 ( 1 ): 50 .

SCHWARZ K M , GROSSE-HONEBRINK A , DERECKA K , et al . Towards improved butanol production through targeted genetic modification of Clostridium pasteurianum [J ] . Metabolic Engineering , 2017 , 40 : 124 - 137 .

SUN S Q , SHU L , LU X Y , et al . 1,2-Propanediol production from glycerol via an endogenous pathway of Klebsiella pneumoniae [J ] . Applied Microbiology and Biotechnology , 2021 , 105 ( 23 ): 9003 - 9016 .

KIM S J , HAHN J S . Efficient production of 2,3-butanediol in Saccharomyces cerevisiae by eliminating ethanol and glycerol production and redox rebalancing [J ] . Metabolic Engineering , 2015 , 31 : 94 - 101 .

CHEN Z Y , YU S Z , LIU J , et al . Concentration recognition-based auto-dynamic regulation system (CRUISE) enabling efficient production of higher alcohols [J ] . Advanced Science , 2024 , 11 ( 23 ): 2310215 .

SOH L M J , MAK W S , LIN P P , et al . Engineering a thermostable keto acid decarboxylase using directed evolution and computationally directed protein design [J ] . ACS Synthetic Biology , 2017 , 6 ( 4 ): 610 - 618 .

SUTIONO S , CARSTEN J , SIEBER V . Structure-guided engineering of α-keto acid decarboxylase for the production of higher alcohols at elevated temperature [J ] . ChemSusChem , 2018 , 11 ( 18 ): 3335 - 3344 .

JANG Y S , YANG J , KIM J K , et al . Adaptive laboratory evolution and transcriptomics-guided engineering of Escherichia coli for increased isobutanol tolerance [J ] . Biotechnology Journal , 2024 , 19 ( 1 ): 2300270 .

KNOSHAUG E P , ZHANG M . Butanol tolerance in a selection of microorganisms [J ] . Applied Biochemistry and Biotechnology , 2009 , 153 ( 1 ): 13 - 20 .

RÜHL J , SCHMID A , BLANK L M . Selected Pseudomonas putida strains able to grow in the presence of high butanol concentrations [J ] . Applied and Environmental Microbiology , 2009 , 75 ( 13 ): 4653 - 4656 .

ZAKI A M , WIMALASENA T T , GREETHAM D . Phenotypic characterisation of Saccharomyces spp. for tolerance to 1-butanol [J ] . Journal of Industrial Microbiology & Biotechnology , 2014 , 41 ( 11 ): 1627 - 1636 .

KATAOKA N , TAJIMA T , KATO J , et al . Development of butanol-tolerant Bacillus subtilis strain GRSW2-B1 as a potential bioproduction host [J ] . AMB Express , 2011 , 1 : 10 .

KURTH E G , DOUGHTY D M , BOTTOMLEY P J , et al . Involvement of BmoR and BmoG in n -alkane metabolism in ‘ Pseudomonas butanovora’ [J ] . Microbiology , 2008 , 154 ( Pt 1 ): 139 - 147 .

KIM N M , SINNOTT R W , ROTHSCHILD L N , et al . Elucidation of sequence-function relationships for an improved biobutanol in vivo biosensor in E . coli [J ] . Frontiers in Bioengineering and Biotechnology , 2022 , 10 : 821152 .

SATHESH-PRABU C , TIWARI R , KIM D , et al . Inducible and tunable gene expression systems for Pseudomonas putida KT2440 [J ] . Scientific Reports , 2021 , 11 : 18079 .

COBAN I , LAMPING J P , HIRSCH A G , et al . dsRNA formation leads to preferential nuclear export and gene expression [J ] . Nature , 2024 , 631 ( 8020 ): 432 - 438 .

GILBERT L A , LARSON M H , MORSUT L , et al . CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes [J ] . Cell , 2013 , 154 ( 2 ): 442 - 451 .

CANVER M C , SMITH E C , SHER F , et al . BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis [J ] . Nature , 2015 , 527 ( 7577 ): 192 - 197 .

KORKMAZ G , LOPES R , UGALDE A P , et al . Functional genetic screens for enhancer elements in the human genome using CRISPR-Cas9 [J ] . Nature Biotechnology , 2016 , 34 ( 2 ): 192 - 198 .

SANJANA N E , WRIGHT J , ZHENG K J , et al . High-resolution interrogation of functional elements in the noncoding genome [J ] . Science , 2016 , 353 ( 6307 ): 1545 - 1549 .

REILLY S K , GOSAI S J , GUTIERREZ A , et al . Direct characterization of cis -regulatory elements and functional dissection of complex genetic associations using HCR-FlowFISH [J ] . Nature Genetics , 2021 , 53 ( 8 ): 1166 - 1176 .

GASPERINI M , HILL A J , MCFALINE-FIGUEROA J L , et al . A genome-wide framework for mapping gene regulation via cellular genetic screens [J ] . Cell , 2019 , 176 ( 6 ): 1516 .

THAKORE P I , D’IPPOLITO A M , SONG L Y , et al . Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements [J ] . Nature Methods , 2015 , 12 ( 12 ): 1143 - 1149 .

NASSER J , BERGMAN D T , FULCO C P , et al . Genome-wide enhancer maps link risk variants to disease genes [J ] . Nature , 2021 , 593 ( 7858 ): 238 - 243 .

CHEN Z Y , JAVED N , MOORE M , et al . Integrative dissection of gene regulatory elements at base resolution [J ] . Cell Genomics , 2023 , 3 ( 6 ): 100318 .

MOORE M M , WEKHANDE S , ISSNER R , et al . Multi-locus CRISPRi targeting with a single truncated guide RNA [J ] . Nature Communications , 2025 , 16 : 1357 .

YU Y Y , GAWLITT S , DE ANDRADE E SOUSA L B , et al . Improved prediction of bacterial CRISPRi guide efficiency from depletion screens through mixed-effect machine learning and data integration [J ] . Genome Biology , 2024 , 25 ( 1 ): 13 .

JUNG D , LIU B Y , HE X P , et al . Accessing previously uncultured marine microbial resources by a combination of alternative cultivation methods [J ] . Microbial Biotechnology , 2021 , 14 ( 3 ): 1148 - 1158 .

KAWAI R , TOYA Y , MIYOSHI K , et al . Acceleration of target production in co-culture by enhancing intermediate consumption through adaptive laboratory evolution [J ] . Biotechnology and Bioengineering , 2022 , 119 ( 3 ): 936 - 945 .

PANDE S , MERKER H , BOHL K , et al . Fitness and stability of obligate cross-feeding interactions that emerge upon gene loss in bacteria [J ] . The ISME Journal , 2014 , 8 ( 5 ): 953 - 962 .

KARIM A , ISLAM M A , BIN KHALID Z , et al . Microbial lipid accumulation through bioremediation of palm oil mill effluent using a yeast-bacteria co-culture [J ] . Renewable Energy , 2021 , 176 : 106 - 114 .

SUN Y , LIU W C , SHI X , et al . Inducing secondary metabolite production of Aspergillus sydowii through microbial co-culture with Bacillus subtilis [J ] . Microbial Cell Factories , 2021 , 20 ( 1 ): 42 .

LIN Z N , LIU H J , CONG W , et al . Continuous fermentation coupled with online gas stripping for effective biobutanol production [J ] . Fermentation , 2023 , 9 ( 11 ): 942 .

BAEZ A , CHO K M , LIAO J C . High-flux isobutanol production using engineered Escherichia coli : a bioreactor study with in situ product removal [J ] . Applied Microbiology and Biotechnology , 2011 , 90 ( 5 ): 1681 - 1690 .

DING T T , LIANG Z Y , YANG Y , et al . Rapidly engineering an osmotic-pressure-tolerant gut bacterium for efficient non-sterile production of bulk chemicals [J ] . Chemical Engineering Journal , 2024 , 491 : 152076 .

BASEN M , SCHUT G J , NGUYEN D M , et al . Single gene insertion drives bioalcohol production by a thermophilic archaeon [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2014 , 111 ( 49 ): 17618 - 17623 .

XU P , LI L Y , ZHANG F M , et al . Improving fatty acids production by engineering dynamic pathway regulation and metabolic control [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2014 , 111 ( 31 ): 11299 - 11304 .

DAVID F , NIELSEN J , SIEWERS V . Flux control at the malonyl-CoA node through hierarchical dynamic pathway regulation in Saccharomyces cerevisiae [J ] . ACS Synthetic Biology , 2016 , 5 ( 3 ): 224 - 233 .

ANDREOZZI S , CHAKRABARTI A , SOH K C , et al . Identification of metabolic engineering targets for the enhancement of 1,4-butanediol production in recombinant E . coli using large-scale kinetic models [J ] . Metabolic Engineering , 2016 , 35 : 148 - 159 .

BOOB A G , ZHU Z X , INTASIAN P , et al . CRISPR-COPIES: an in silico platform for discovery of neutral integration sites for CRISPR/Cas-facilitated gene integration [J ] . Nucleic Acids Research , 2024 , 52 ( 6 ): e30 .

ABRAMSON J , ADLER J , DUNGER J , et al . Accurate structure prediction of biomolecular interactions with AlphaFold 3 [J ] . Nature , 2024 , 630 ( 8016 ): 493 - 500 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Progress in the construction of microbial cell factories for efficient biofuel production

Synthetic biology-powered cell membrane-derived nanoparticles for precision theranostics

Construction of microbial cell factories for aspartate-family feed amino acids

Related Author

FANG Xinyi

YUE Haitao

YAN Xiongying

WANG Zhen

LOU Jiyun

ZHANG Haoyu

HUANG Xingyu

WANG Xia

Related Institution

Xinjiang University

State Key Laboratory of Biocatalysis and Enzyme Engineering， School of Life Sciences， Hubei University

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety， CAS Center for Excellence in Nanoscience， National Center for Nanoscience and Technology of China

School of Nanoscience and Engineering， University of Chinese Academy of Sciences

College of Materials Science and Opto-Electronic Technology， University of Chinese Academy of Sciences

⁰