微生物合成高级醇的发展趋势与挑战

doi:10.12211/2096-8280.2025-006

合成生物学

• 特约评述 •

微生物合成高级醇的发展趋势与挑战

方馨仪¹, 孙丽超², 霍毅欣², 王颖³, 岳海涛¹

^1.新疆大学，新疆维吾尔自治区乌鲁木齐 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

收稿日期:2025-01-21 修回日期:2025-04-18 出版日期:2025-04-22
通讯作者: 王颖,岳海涛
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，北京理工大学特别研究员，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
基金资助:
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);新疆自治区重点研发任务专项(2023B02034);新疆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)

Trends and challenges in microbial synthesis of higher alcohols

FANG Xinyi¹, SUN Lichao², HUO Yixin², WANG Ying³, YUE Haitao¹

^1.Xinjiang University，Urumqi 830000，Xinjiang，China
^2.Key Laboratory of Molecular Medicine and Biotherapy，School of Life Science，Beijing Institute of Technology，Beijing 100081，China
^3.Key Laboratory of Medicinal Molecule Science and Pharmaceutical Engineering，Ministry of Industry and Information Technology，Institute of Biochemical Engineering，School of Chemistry and Chemical Engineering，Beijing Institute of Technology，Beijing 100081，China

Received:2025-01-21 Revised:2025-04-18 Online:2025-04-22
Contact: WANG Ying, YUE Haitao

摘要/Abstract

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。

关键词: 生物燃料, 高级醇, 合成途径, 代谢工程, 合成生物学

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, 1,3-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.

Key words: biofuels, higher alcohols, synthetic pathway, metabolic engineering, synthetic biology

中图分类号:

Q816

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, 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, DOI: 10.12211/2096-8280.2025-006.

图/表 6

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产物 Products	宿主 Hosts	基因类型（敲除；过表达） Genotypes (knockout; overexpression)	底物 Substrates	发酵条件 Fermentation conditions	产量 Titer (g/L)	参考文献 References
n-PrOH	Escherichia coli	ΔilvA ΔilvB; kivD adh2 cimA^mut leuABCD	Glucose	Shake flask	2.78	[70]
n-PrOH	E. coli	ΔlacI ΔlysA ΔmetA ΔtdhA ΔiclR ΔilvIH ΔilvBNΔrpoS thrA^C1034T lysC^C1005T	Glycerol	Bioreactor (Fed-batch)	10.3	[71]
IPA	E. coli	None; lacI^q thl atoDA adc adhB-593	Glucose	Stirred flask	143	[72]
	E. coli	None; thl atoDA adc adhB-593 bgl-blc	Cellobiose	Shake flask	4.1	[73]
	E. coli	None; thl ctfAB adc adhB-593	Glucose	Shake baffled flask	13.6	[74]
Alcohol mixture	Clostridium acetobutylicum	Δbuk:: ermC; adc ctfAB adhB-593	Glucose	Bioreactor	35	[75]
Alcohol mixture	C. acetobutylicum	Δbuk ΔC1502; adc ctfAB adhB-593	Glucose	Bioreactor	20.4	[76]
n-BuOH	Synechococcus elongatus	None; atoB, hbd, crt, ter, AdhE2	CO₂	Flask and bioreactor	0.015	[77]
	S. elongatus	None; nphT7 phaB aphaJ ter bld yqhD	CO₂	Static capped flask	0.029 9	[78]
	Clostridium tyrobutyricum	Δpta Δbuk; adhE^D485G	Glucose	Bioreactor	130	[79]
	C. tyrobutyricum	None; adhE2	Mannitol	Bioreactor; anaerobic	20.5	[80]
	S. cerevisiae	None; thl, hbd, crt, bcd, etfAB, adhE2	Galactose	Shake flask	0.002 5	[81]
	Pseudomonas putida	None; thl, hbd, crt, bcd, etfAB, adhE2	Glycerol	Shake flask	0.024	[82]
	P. putida	None; thl, hbd, crt, bcd, etfAB, adhE1	Glycerol	Shake flask	0.122	[82]
	Lactobacillus brevis	None; thl, hbd, crt, bcd, etfAB	Glucose	Vial	0.3	[83]
	Clostridium ljungdahlii	None; thlA, hbd, crt, bcd, adhE, and bdhA	Syngas	Shake flask	0.148	[84]
	E. coli	ΔldhA ΔadhE ΔfrdBC Δpta;atoB hbd crt adhE2 fdh ter	Glucose	Bioreactor; anaerobic	30	[85]
IBOH	E. coli	ΔadhE ΔldhA ΔfrdBC Δfnr Δpta ΔpflB;alsS ilvCD kivD adh2	Glucose	Static capped flask	22	[8]
	E. coli	None; alsS ilvCD kivD adhA	Glucose	Bioreactor;	56	[86]
	S. elongatus	None; alsS, ilvCD, kivd, yqhD	CO₂	Bottle	0.450	[87]
	Corynebacterium crenatum	None; ILV2, ILV3, ILV5, kivD, ADH6	Lignocellulose	Bottle	5.61	[88]
	Bacillus megaterium	None; kivd, yqhD	Glucose	Test tube	0.3	[89]
	Bacillus subtilis	Δldh; ilvCD alsS kivD adh2	Glucose	Bioreactor	3.83	[90]
	Clostridium cellulolyticum	None; kivD yqhD alsS ilvCD	Cellulose	Not specified	0.66	[91]
	Corynebacterium glutamicum	ΔaceE Δpqo ΔilvE ΔldhA Δmdh;ilvBNCD pntAB kivD adhA	Glucose	Bioreactor	13	[92]
	Ralstonia eutropha	ΔphaB2C2 ΔphaC1AB1;alsS ilvCD kivD yqhD	CO₂	Bioreactor with electrodes	0.09	[93]
	R. eutropha	ΔphaCAB ΔilvE ΔbkdAB ΔaceE;adh ilvBHCD kivD	Fructose	Shake flask	0.27	[94]
	S. cerevisiae	Δlpd; kivD ADH6 ILV2 ILV5c ILV3c ILV2C MAE1	Glucose	Shake flask	1.62	[95]
	Zymomonas mobilis	None; kdcA Pgap als ilvC ilvD	Glucose	Shake flask	4	[96]
	Clostridium thermocellum	Δhpt; kivd, alsS, ilvBN, ilvCD, ilvD	Cellulose	Consolidated bioprocessing	5.4	[97]
	C. glutamicum	ΔilvE; ilvBNC, ilvD, adhA, kivd	Glucose	Shake flask	20.8	[69]
2-BuOH	Lactobacillus diolivorans	None; pduQ, PDO-DH (NAD(P)H)	meso-2, 3-butanediol/glycerol	Bioreactor	13.4	[98]
	Klebsiella pneumoniae	ΔldhA; pduCDEGH^Q337A^or^F375I, adh	Glucose	Shake flask	1.03	[99]
	L. brevis	None; None	meso-2, 3-butanediol	Test tube	0.88	[100]
	Lactobacillus buchneri	None; None	butaNone	Test tube	0.04	[100]
	S. cerevisiae	None; pduCDEGH, adh	meso-2, 3‐butanediol	Shake flask	0.004	[101]
	Lactobacillus spp.	None; None	meso-2, 3‐butanediol	Shake flask	0.41	[102]
2M1B	E. coli	ΔmetA Δtdh; ilvGM ilvCD ilvA kivD adh2 thrABC	Glucose	Shake baffled flask	1.25	[7]
	Brevibacterium flavum	None; ilvC-ilvD-alsS, kivd-ADH2	Glucose; duckweed	Shake flash	19.5/17.5	[103]
	C. crenatum	None; Cgl1271, Cgl1273, Cgl1268, kivd; adh2	Glucose	Shake flash	5.26	[104]
3M1B	E. coli	None; alsS ilvCD kivD adh2 leuA^G462D leuBCD	Glucose	Shake flask	9.5	[105]
	B. flavum	None; ilvC-ilvD-alsS, kivd-ADH2	Glucose; duckweed	Shake flask	0.79/0.78	[103]
	C. crenatum	None; Cgl1271, Cgl1273, Cgl1268, kivd; adh2	Glucose	Shake flask	3.78	[104]
2,3-BDO	Serratia marcescens	swrI, swrR, slaA, slaB, slaC, slaR; swrR	Glucose	Shake flask	42.5	[106]
	S. marcescens	ΔswrW; swrW	Sucrose	Fed-batch	152	[107]
	Z. mobilis	ΔPDC; LlkivD, ARO10, THI3, ADH6, ADH7, PpIlv2, PpIlv6, PpIlv5, PpIlv3, ScATF1	Glucose	Shake flask	13.3	[108]
	E. coli	None; budB, budA, budC	Glucose	Shake flask	meso-17.7	[109]
	E. coli	None; alsS, alsD, bdhA from K. pneumoniae	Glucose	Shake flask	(R, R)-5.8	[110]
	E. coli	None; alsS, alsD, adh from C. beijerinckii	Glucose	Shake flask	(R, R)-5.1	[110]
	E. coli	None; alsS, alsD, adh from T. brockii	Glucose	Shake flask	(R, R)-6.1	[110]
	E. coli	None; budA, budB, ydjL	Glucose	Shake flask	(S, S)-2.2	[111]
	E. coli	None; budA, budB, ydjL	Glucose	Shake flask	0.66	[112]
	E. coli	None; budA, budB, ydjL	Glucose	Bioreactor	(R, R)-30.5	[113]
	E. coli	ΔldhA, ΔpflB, ΔadhE, ΔlpdA::K.p.lpd E354 K, Δmdh, ΔarcA; gltAR164L, ilvBN,aldB, bdh1	Glucose	Bioreactor	88	[114]
	E. coli	None; budA, budB, budC	Glucose	Bioreactor High oxygen	52.1	[115]
	E. coli	ΔldhA, ΔadhE, Δpta, ΔfrdA; budA,budB, budC	Glucose	Bioreactor Low oxygen	68.1	[115]
	E. coli	ΔldhA, Δpta, ΔadhE, ΔpoxB; alaS, alsD, budC	Glucose	Shake flask	meso-14.5	[116]
	E. coli	None; bdh, fdh	Diacetyl	Bioreactor	(S, S)-31.7	[117]
	E. coli	None; budC, bdh	Diacetyl	Shake flask	(S, S)-2.2	[118]
	E. coli	None; budA, budB, budC	Sugar beet molasses	Fed-batch	56.2	[115]
	E. coli	ΔfrdABCD, ΔldhA, ΔadhE, ΔlpdA, Δpta; budB, budA, budC	Algal hydrolysate	Shake flask	meso-(S, S)-14.1	[119]
	E. coli	ΔpoxB, ΔldhA, ΔackA, Δpta; alsS, alsD, budC, ced3A	Cellodextrin	Shake flask	meso-5.5	[120]
1,3-PDO	E. coli	ΔgldA, ΔglpK, ΔaldA, ΔaldB, ΔmgsA, ΔptsHI, replacing gapA promoter with the synthetic short 1.5 GI promoter (SEQ ID NO:28); galP	Glucose	Bioreactor	112	[121]
	E. coli	None; gpd1-gpp2 fusion gene, dha operon, rpoS	Glucose	Bioreactor	12.1	[122]
	E. coli	None; dhaB, yqhD, gdrA, gdrB, fdh1, gapN, galP, glk	Glycerol	Shake flask	13.47	[123]
	E. coli	None; dhaB1, dhaB2, yqhD	Glycerol	Bioreactor	104.4	[124]
	E. coli	None; dhaB1, dhaB2, dhaT	Glycerol and glucose	Bioreactor	41.7	[125]
	Corynebacterium glutamicum	Δald, Δpyk, Δadh, ΔpoxB, ΔldhA, Δppc, Δzwf; hdpA-gldA, gpd1, gpp2, yqhD, pduCEDGHDownregulation: gapA	Glucose and xylose	Fed-batch	110.4	[126]
	Vibrio natriegens	Δpta-ackA, ΔarcA, ΔadhE, ΔaldB, Δldh, Δpfl, ΔsthA, ΔglpR, ΔaldA, ΔfrdABCD;pntAB, phaP	Glycerol	Fed-batch	69.5	[127]
	E. coli	ΔthrB;yqhD, lysC, ser^CR42W/R77W, metL, pdc	Glucose	Fed-batch	3.03	[128]
	E. coli	None; mcrC, pduP, mcrN, yqhD, prpE	Glucose; Xylose, Glycerol, Acetate	Shake flask; Fed-batch	2.93; 7.98	[63]
	E. coli	ΔlysC, ΔgltA; ppc	Glucose	Shake flask; Fed-batch	6.41; 11.21;	[129]
	E. coli	ΔglpK, ΔptsG; yqhD, pntAB, galP, glk	Isoprene	Shake flask	2.5	[130]
1,3-BDO	E. coli	None; phaAB, bld	Glucose	Fed-batch	15.76	[131]
	E. coli	Δldh, Δpta, ΔackA, ΔadhE; bld^L273T, yqhD, phaAB, pntAB	Glucose	Optimized fermentation	13.40	[132]
	E. coli	Δldh, Δpta, ΔackA, ΔadhE; phaAB, yqhD, pntAB, car, sfp	Glucose	Optimized fermentation	0.40	[132]
	E. coli	Δzwf, Δedd, ΔpfkA, ΔpfkB; pk, glpX, thl, hbd, tesB, car	Glucose	Fed-batch	22.66	[133]
	E. coli	ΔadhE, ΔpoxB, ΔldhA, Δpta-ackA, ΔatoB, ΔtesB, ΔyciA; phaAB, bld, yqhD	Glucose	Fed-batch	23.13	[134]
	E. coli	ΔadhE, ΔpoxB, ΔldhA, ΔyciA, ΔpdhR, Δpgi, ΔgntR; phaAB, bld, yjgB, zwf	Glucose	Fed-batch	71.1	[135]
	E. coli	Δpta, ΔyjgB, ΔadhE, ΔldhA, ΔpflB, ΔadhP, ΔyqhD, ΔeutG, ΔilvB, ΔpoxB; AKR,DERA, PDC	Acetaldehyd; 3-Hydroxybutanal (3-HB)	Biotransformation	2.4	[136]
1,4-BDO	E. coli	Δsad::cat2-bld-bdh, ΔlacZ::cat1-sucD 4hbd, ΔllpdA::K.p.lpdA D354KΔpflB, ΔarcA, Δmdh, ΔadhE, ΔldhA, knock down tesB; gabD, ybgC, gltAR163L	Glucose	Bioreactor	1.8	[137]
	E. coli	ΔadhE, ΔldhA, ΔpflB, Δmdh, ΔarcA, lpdA::K.p.lpdD354K; gltAR163L, sucA, 4hbd, cat2, ald, adh	Glucose	Bioreactor	18	[66]
	E. coli	ΔaraA, Δicd; araC, araD, araA, araB, araE, kivd, yqhd	L-Arabinose	Bioreactor	1.51	[138]
	E. coli	None; None	Glucose	Commercial-scale fermentation	>125	[139]
	E. coli	None; gadB, gabT, yqhD, car, ppc, gltA^R163L	Amino acids (AAs), Glucose	General metabolic platform	1.41	[140]
	E. coli	ΔyagE, ΔxylA, ΔyjhH; Kvid^V461I,xylBCDX, yqhD	Glucose, Xylose	D-xylose, L-arabinose, D-galacturonate	12	[141]
	E. coli	ΔuxaC, ΔgarL, Δicd; udh, garD, ycbC, xylA(CC), kivd, yqhd	D-Galacturonate	Bioreactor	16.5	[138]
	E. coli	ΔxylA, ΔyjhH, ΔyagE, Δicd; xylB, xylC, xylD, xylX, xylA(CC), kivdV461I, yqhd	Xylose	Bioreactor	12	[138]
1,2-PDO	E. coli	ΔpoxB, ΔfrdA, ΔmgsA, ΔadhE::pdcD;gldA, mgs	Glucose	Shake flask	0.7	[142]
	E. coli	ΔlldD::mmsB, ΔackA-pta::pct, ΔldhA::Lldh; pct, pdcD, mmsB	Glucose	Shake flask	1.04	[4]
	E. coli	ΔldhA::KanR;mgs, gldA, fucO	Glucose	Bioreactor	4.5	[143]
	E. coli	Δzwf, ΔtpiA, ΔgloA, ΔldhA, ΔadhE,;mgsA, gldA, fucO	Glucose	Shake flask	5.13	[121]
	E. coli	ΔlldD, Δdld, ΔldhA, ΔadhE; pct, pduP, yahK	D-/L-Lactate	Shake flask	(R)-1.5; (S)-1.7	[144]
	E. coli	Δac kA-pta, ΔldhA, ΔdhaK; dhaKL, gldA, mgsA, yqhD	Glycerol	Bioreactor	5.6	[145]
BT	E. coli	ΔyiaE, ΔycdW, ΔxylA KivD (Lactococcus lactis); None	Xylose	Fed-batch, carbon flux optimization	10.03	[146]
	E. coli	None; YqhD, YjhG	Xylose	Optimized cultivation	5.1	[147]
	E. coli	ΔxylA, ΔxylB, ΔyjhE, ΔyagH, ΔycdW;xdh, mdlC	Xylose	Fed-batch	2.38	[148]
	E. coli	None; XylD, KdcA (Lactococcus lactis), AdhP (E. coli)	Xylose	Optimized cultivation	5.1	[149]
	E. coli	ΔfadE; XylD, fadD	Xylose, free fatty acids	Fed-batch	1.1 (BT esters)	[150]
	S. cerevisiae	None; XylB, XylD	Xylose, rice straw hydrolysate	Aerobic fermentation	1.7	[151]

产物 Products	宿主 Hosts	基因类型（敲除；过表达） Genotypes (knockout; overexpression)	底物 Substrates	发酵条件 Fermentation conditions	产量 Titer (g/L)	参考文献 References
n-PrOH	Escherichia coli	ΔilvA ΔilvB; kivD adh2 cimA^mut leuABCD	Glucose	Shake flask	2.78	[70]
n-PrOH	E. coli	ΔlacI ΔlysA ΔmetA ΔtdhA ΔiclR ΔilvIH ΔilvBNΔrpoS thrA^C1034T lysC^C1005T	Glycerol	Bioreactor (Fed-batch)	10.3	[71]
IPA	E. coli	None; lacI^q thl atoDA adc adhB-593	Glucose	Stirred flask	143	[72]
	E. coli	None; thl atoDA adc adhB-593 bgl-blc	Cellobiose	Shake flask	4.1	[73]
	E. coli	None; thl ctfAB adc adhB-593	Glucose	Shake baffled flask	13.6	[74]
Alcohol mixture	Clostridium acetobutylicum	Δbuk:: ermC; adc ctfAB adhB-593	Glucose	Bioreactor	35	[75]
Alcohol mixture	C. acetobutylicum	Δbuk ΔC1502; adc ctfAB adhB-593	Glucose	Bioreactor	20.4	[76]
n-BuOH	Synechococcus elongatus	None; atoB, hbd, crt, ter, AdhE2	CO₂	Flask and bioreactor	0.015	[77]
	S. elongatus	None; nphT7 phaB aphaJ ter bld yqhD	CO₂	Static capped flask	0.029 9	[78]
	Clostridium tyrobutyricum	Δpta Δbuk; adhE^D485G	Glucose	Bioreactor	130	[79]
	C. tyrobutyricum	None; adhE2	Mannitol	Bioreactor; anaerobic	20.5	[80]
	S. cerevisiae	None; thl, hbd, crt, bcd, etfAB, adhE2	Galactose	Shake flask	0.002 5	[81]
	Pseudomonas putida	None; thl, hbd, crt, bcd, etfAB, adhE2	Glycerol	Shake flask	0.024	[82]
	P. putida	None; thl, hbd, crt, bcd, etfAB, adhE1	Glycerol	Shake flask	0.122	[82]
	Lactobacillus brevis	None; thl, hbd, crt, bcd, etfAB	Glucose	Vial	0.3	[83]
	Clostridium ljungdahlii	None; thlA, hbd, crt, bcd, adhE, and bdhA	Syngas	Shake flask	0.148	[84]
	E. coli	ΔldhA ΔadhE ΔfrdBC Δpta;atoB hbd crt adhE2 fdh ter	Glucose	Bioreactor; anaerobic	30	[85]
IBOH	E. coli	ΔadhE ΔldhA ΔfrdBC Δfnr Δpta ΔpflB;alsS ilvCD kivD adh2	Glucose	Static capped flask	22	[8]
	E. coli	None; alsS ilvCD kivD adhA	Glucose	Bioreactor;	56	[86]
	S. elongatus	None; alsS, ilvCD, kivd, yqhD	CO₂	Bottle	0.450	[87]
	Corynebacterium crenatum	None; ILV2, ILV3, ILV5, kivD, ADH6	Lignocellulose	Bottle	5.61	[88]
	Bacillus megaterium	None; kivd, yqhD	Glucose	Test tube	0.3	[89]
	Bacillus subtilis	Δldh; ilvCD alsS kivD adh2	Glucose	Bioreactor	3.83	[90]
	Clostridium cellulolyticum	None; kivD yqhD alsS ilvCD	Cellulose	Not specified	0.66	[91]
	Corynebacterium glutamicum	ΔaceE Δpqo ΔilvE ΔldhA Δmdh;ilvBNCD pntAB kivD adhA	Glucose	Bioreactor	13	[92]
	Ralstonia eutropha	ΔphaB2C2 ΔphaC1AB1;alsS ilvCD kivD yqhD	CO₂	Bioreactor with electrodes	0.09	[93]
	R. eutropha	ΔphaCAB ΔilvE ΔbkdAB ΔaceE;adh ilvBHCD kivD	Fructose	Shake flask	0.27	[94]
	S. cerevisiae	Δlpd; kivD ADH6 ILV2 ILV5c ILV3c ILV2C MAE1	Glucose	Shake flask	1.62	[95]
	Zymomonas mobilis	None; kdcA Pgap als ilvC ilvD	Glucose	Shake flask	4	[96]
	Clostridium thermocellum	Δhpt; kivd, alsS, ilvBN, ilvCD, ilvD	Cellulose	Consolidated bioprocessing	5.4	[97]
	C. glutamicum	ΔilvE; ilvBNC, ilvD, adhA, kivd	Glucose	Shake flask	20.8	[69]
2-BuOH	Lactobacillus diolivorans	None; pduQ, PDO-DH (NAD(P)H)	meso-2, 3-butanediol/glycerol	Bioreactor	13.4	[98]
	Klebsiella pneumoniae	ΔldhA; pduCDEGH^Q337A^or^F375I, adh	Glucose	Shake flask	1.03	[99]
	L. brevis	None; None	meso-2, 3-butanediol	Test tube	0.88	[100]
	Lactobacillus buchneri	None; None	butaNone	Test tube	0.04	[100]
	S. cerevisiae	None; pduCDEGH, adh	meso-2, 3‐butanediol	Shake flask	0.004	[101]
	Lactobacillus spp.	None; None	meso-2, 3‐butanediol	Shake flask	0.41	[102]
2M1B	E. coli	ΔmetA Δtdh; ilvGM ilvCD ilvA kivD adh2 thrABC	Glucose	Shake baffled flask	1.25	[7]
	Brevibacterium flavum	None; ilvC-ilvD-alsS, kivd-ADH2	Glucose; duckweed	Shake flash	19.5/17.5	[103]
	C. crenatum	None; Cgl1271, Cgl1273, Cgl1268, kivd; adh2	Glucose	Shake flash	5.26	[104]
3M1B	E. coli	None; alsS ilvCD kivD adh2 leuA^G462D leuBCD	Glucose	Shake flask	9.5	[105]
	B. flavum	None; ilvC-ilvD-alsS, kivd-ADH2	Glucose; duckweed	Shake flask	0.79/0.78	[103]
	C. crenatum	None; Cgl1271, Cgl1273, Cgl1268, kivd; adh2	Glucose	Shake flask	3.78	[104]
2,3-BDO	Serratia marcescens	swrI, swrR, slaA, slaB, slaC, slaR; swrR	Glucose	Shake flask	42.5	[106]
	S. marcescens	ΔswrW; swrW	Sucrose	Fed-batch	152	[107]
	Z. mobilis	ΔPDC; LlkivD, ARO10, THI3, ADH6, ADH7, PpIlv2, PpIlv6, PpIlv5, PpIlv3, ScATF1	Glucose	Shake flask	13.3	[108]
	E. coli	None; budB, budA, budC	Glucose	Shake flask	meso-17.7	[109]
	E. coli	None; alsS, alsD, bdhA from K. pneumoniae	Glucose	Shake flask	(R, R)-5.8	[110]
	E. coli	None; alsS, alsD, adh from C. beijerinckii	Glucose	Shake flask	(R, R)-5.1	[110]
	E. coli	None; alsS, alsD, adh from T. brockii	Glucose	Shake flask	(R, R)-6.1	[110]
	E. coli	None; budA, budB, ydjL	Glucose	Shake flask	(S, S)-2.2	[111]
	E. coli	None; budA, budB, ydjL	Glucose	Shake flask	0.66	[112]
	E. coli	None; budA, budB, ydjL	Glucose	Bioreactor	(R, R)-30.5	[113]
	E. coli	ΔldhA, ΔpflB, ΔadhE, ΔlpdA::K.p.lpd E354 K, Δmdh, ΔarcA; gltAR164L, ilvBN,aldB, bdh1	Glucose	Bioreactor	88	[114]
	E. coli	None; budA, budB, budC	Glucose	Bioreactor High oxygen	52.1	[115]
	E. coli	ΔldhA, ΔadhE, Δpta, ΔfrdA; budA,budB, budC	Glucose	Bioreactor Low oxygen	68.1	[115]
	E. coli	ΔldhA, Δpta, ΔadhE, ΔpoxB; alaS, alsD, budC	Glucose	Shake flask	meso-14.5	[116]
	E. coli	None; bdh, fdh	Diacetyl	Bioreactor	(S, S)-31.7	[117]
	E. coli	None; budC, bdh	Diacetyl	Shake flask	(S, S)-2.2	[118]
	E. coli	None; budA, budB, budC	Sugar beet molasses	Fed-batch	56.2	[115]
	E. coli	ΔfrdABCD, ΔldhA, ΔadhE, ΔlpdA, Δpta; budB, budA, budC	Algal hydrolysate	Shake flask	meso-(S, S)-14.1	[119]
	E. coli	ΔpoxB, ΔldhA, ΔackA, Δpta; alsS, alsD, budC, ced3A	Cellodextrin	Shake flask	meso-5.5	[120]
1,3-PDO	E. coli	ΔgldA, ΔglpK, ΔaldA, ΔaldB, ΔmgsA, ΔptsHI, replacing gapA promoter with the synthetic short 1.5 GI promoter (SEQ ID NO:28); galP	Glucose	Bioreactor	112	[121]
	E. coli	None; gpd1-gpp2 fusion gene, dha operon, rpoS	Glucose	Bioreactor	12.1	[122]
	E. coli	None; dhaB, yqhD, gdrA, gdrB, fdh1, gapN, galP, glk	Glycerol	Shake flask	13.47	[123]
	E. coli	None; dhaB1, dhaB2, yqhD	Glycerol	Bioreactor	104.4	[124]
	E. coli	None; dhaB1, dhaB2, dhaT	Glycerol and glucose	Bioreactor	41.7	[125]
	Corynebacterium glutamicum	Δald, Δpyk, Δadh, ΔpoxB, ΔldhA, Δppc, Δzwf; hdpA-gldA, gpd1, gpp2, yqhD, pduCEDGHDownregulation: gapA	Glucose and xylose	Fed-batch	110.4	[126]
	Vibrio natriegens	Δpta-ackA, ΔarcA, ΔadhE, ΔaldB, Δldh, Δpfl, ΔsthA, ΔglpR, ΔaldA, ΔfrdABCD;pntAB, phaP	Glycerol	Fed-batch	69.5	[127]
	E. coli	ΔthrB;yqhD, lysC, ser^CR42W/R77W, metL, pdc	Glucose	Fed-batch	3.03	[128]
	E. coli	None; mcrC, pduP, mcrN, yqhD, prpE	Glucose; Xylose, Glycerol, Acetate	Shake flask; Fed-batch	2.93; 7.98	[63]
	E. coli	ΔlysC, ΔgltA; ppc	Glucose	Shake flask; Fed-batch	6.41; 11.21;	[129]
	E. coli	ΔglpK, ΔptsG; yqhD, pntAB, galP, glk	Isoprene	Shake flask	2.5	[130]
1,3-BDO	E. coli	None; phaAB, bld	Glucose	Fed-batch	15.76	[131]
	E. coli	Δldh, Δpta, ΔackA, ΔadhE; bld^L273T, yqhD, phaAB, pntAB	Glucose	Optimized fermentation	13.40	[132]
	E. coli	Δldh, Δpta, ΔackA, ΔadhE; phaAB, yqhD, pntAB, car, sfp	Glucose	Optimized fermentation	0.40	[132]
	E. coli	Δzwf, Δedd, ΔpfkA, ΔpfkB; pk, glpX, thl, hbd, tesB, car	Glucose	Fed-batch	22.66	[133]
	E. coli	ΔadhE, ΔpoxB, ΔldhA, Δpta-ackA, ΔatoB, ΔtesB, ΔyciA; phaAB, bld, yqhD	Glucose	Fed-batch	23.13	[134]
	E. coli	ΔadhE, ΔpoxB, ΔldhA, ΔyciA, ΔpdhR, Δpgi, ΔgntR; phaAB, bld, yjgB, zwf	Glucose	Fed-batch	71.1	[135]
	E. coli	Δpta, ΔyjgB, ΔadhE, ΔldhA, ΔpflB, ΔadhP, ΔyqhD, ΔeutG, ΔilvB, ΔpoxB; AKR,DERA, PDC	Acetaldehyd; 3-Hydroxybutanal (3-HB)	Biotransformation	2.4	[136]
1,4-BDO	E. coli	Δsad::cat2-bld-bdh, ΔlacZ::cat1-sucD 4hbd, ΔllpdA::K.p.lpdA D354KΔpflB, ΔarcA, Δmdh, ΔadhE, ΔldhA, knock down tesB; gabD, ybgC, gltAR163L	Glucose	Bioreactor	1.8	[137]
	E. coli	ΔadhE, ΔldhA, ΔpflB, Δmdh, ΔarcA, lpdA::K.p.lpdD354K; gltAR163L, sucA, 4hbd, cat2, ald, adh	Glucose	Bioreactor	18	[66]
	E. coli	ΔaraA, Δicd; araC, araD, araA, araB, araE, kivd, yqhd	L-Arabinose	Bioreactor	1.51	[138]
	E. coli	None; None	Glucose	Commercial-scale fermentation	>125	[139]
	E. coli	None; gadB, gabT, yqhD, car, ppc, gltA^R163L	Amino acids (AAs), Glucose	General metabolic platform	1.41	[140]
	E. coli	ΔyagE, ΔxylA, ΔyjhH; Kvid^V461I,xylBCDX, yqhD	Glucose, Xylose	D-xylose, L-arabinose, D-galacturonate	12	[141]
	E. coli	ΔuxaC, ΔgarL, Δicd; udh, garD, ycbC, xylA(CC), kivd, yqhd	D-Galacturonate	Bioreactor	16.5	[138]
	E. coli	ΔxylA, ΔyjhH, ΔyagE, Δicd; xylB, xylC, xylD, xylX, xylA(CC), kivdV461I, yqhd	Xylose	Bioreactor	12	[138]
1,2-PDO	E. coli	ΔpoxB, ΔfrdA, ΔmgsA, ΔadhE::pdcD;gldA, mgs	Glucose	Shake flask	0.7	[142]
	E. coli	ΔlldD::mmsB, ΔackA-pta::pct, ΔldhA::Lldh; pct, pdcD, mmsB	Glucose	Shake flask	1.04	[4]
	E. coli	ΔldhA::KanR;mgs, gldA, fucO	Glucose	Bioreactor	4.5	[143]
	E. coli	Δzwf, ΔtpiA, ΔgloA, ΔldhA, ΔadhE,;mgsA, gldA, fucO	Glucose	Shake flask	5.13	[121]
	E. coli	ΔlldD, Δdld, ΔldhA, ΔadhE; pct, pduP, yahK	D-/L-Lactate	Shake flask	(R)-1.5; (S)-1.7	[144]
	E. coli	Δac kA-pta, ΔldhA, ΔdhaK; dhaKL, gldA, mgsA, yqhD	Glycerol	Bioreactor	5.6	[145]
BT	E. coli	ΔyiaE, ΔycdW, ΔxylA KivD (Lactococcus lactis); None	Xylose	Fed-batch, carbon flux optimization	10.03	[146]
	E. coli	None; YqhD, YjhG	Xylose	Optimized cultivation	5.1	[147]
	E. coli	ΔxylA, ΔxylB, ΔyjhE, ΔyagH, ΔycdW;xdh, mdlC	Xylose	Fed-batch	2.38	[148]
	E. coli	None; XylD, KdcA (Lactococcus lactis), AdhP (E. coli)	Xylose	Optimized cultivation	5.1	[149]
	E. coli	ΔfadE; XylD, fadD	Xylose, free fatty acids	Fed-batch	1.1 (BT esters)	[150]
	S. cerevisiae	None; XylB, XylD	Xylose, rice straw hydrolysate	Aerobic fermentation	1.7	[151]

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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

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