Advance on the preparation of itaconic acid by biological method

doi:10.11949/0438-1157.20240830

Abstract

Abstract:

Itaconic acid (IA) is one of the important raw materials in chemical production and one of the most promising high-value-added platform compounds. It can replace petroleum-based acrylic acid and methacrylic acid. Furthermore, itaconic acid possesses significant pharmacological properties, such as anti-inflammatory, antiviral, and immune regulation functions, positioning it as a prospective drug candidate molecule in pharmaceutical research and development. In light of both domestic and international research advancements, this article provides a comprehensive review of the biosynthetic pathways and recent progress in the biosynthesis of itaconic acid. Additionally, it addresses strategies for enhancing itaconic acid production and offers an outlook on prospective research directions in the realm of itaconic acid.

Key words: itaconic acid, biological engineering, process optimization, biocatalysis, synthetic biology

摘要：

衣康酸（itaconic acid，IA）是化工生产中的重要原料之一，是最具发展潜力的高附加值平台化合物之一，可以替代石油基丙烯酸和甲基丙烯酸；也可发挥抗炎、抗病毒和免疫调节等药理作用，有望在医药研发领域成为潜在药物候选分子。结合国内外研究现状，系统综述了衣康酸生物合成途径、生物合成研究进展以及产量提高策略，并对衣康酸的未来研究方向进行展望。

关键词: 衣康酸, 生物工程, 工艺优化, 生物催化, 合成生物学

CLC Number:

Q 74

Jing ZHANG, Yue YUAN, Yanmei LIU, Zhiwen WANG, Tao CHEN. Advance on the preparation of itaconic acid by biological method[J]. CIESC Journal, 2025, 76(3): 909-921.

张静, 元跃, 刘艳梅, 王智文, 陈涛. 生物法制备衣康酸研究进展[J]. 化工学报, 2025, 76(3): 909-921.

Figures/Tables 5

References 96

1	Diankristanti P A, Ng I S. Microbial itaconic acid bioproduction towards sustainable development: insights, challenges, and prospects[J]. Bioresource Technology, 2023, 384: 129280.
2	Zhang R W, Liu H, Ning Y C, et al. Recent advances on the production of itaconic acid via the fermentation and metabolic engineering[J]. Fermentation, 2023, 9(1): 71.
3	Werpy T A, Petersen G, Added T. Top value added chemicals from biomass(volume Ⅰ): Results of screening for potential candidates from sugars and synthesis gas[R]. Golden, CO, United States: National Renewable Energy Laboratory, 2004.
4	Willke T, Vorlop K D. Biotechnological production of itaconic acid[J]. Applied Microbiology and Biotechnology, 2001, 56(3/4): 289-295.
5	Park D S, Abdelrahman O A, Vinter K P, et al. Multifunctional cascade catalysis of itaconic acid hydrodeoxygenation to 3-methyl-tetrahydrofuran[J]. ACS Sustainable Chemistry & Engineering, 2018, 6(7): 9394-9402.
6	Liu C S, Wang Y L, Liu J H, et al. One-step synthesis of 4-octyl itaconate through the structure control of lipase[J]. Journal of Organic Chemistry, 2021, 86(12): 7895-7903.
7	Sano M, Tanaka T, Ohara H, et al. Itaconic acid derivatives: structure, function, biosynthesis, and perspectives[J]. Applied Microbiology and Biotechnology, 2020, 104(21): 9041-9051.
8	Cunha da Cruz J, Machado de Castro A, Camporese Sérvulo E F. World market and biotechnological production of itaconic acid[J]. 3 Biotech, 2018, 8(3): 138.
9	Yang J, Xu H, Jiang J C, et al. Production of itaconic acid through microbiological fermentation of inexpensive materials[J]. Journal of Bioresources and Bioproducts, 2019, 4(3): 135-142.
10	Gopaliya D, Kumar V, Khare S K. Recent advances in itaconic acid production from microbial cell factories[J]. Biocatalysis and Agricultural Biotechnology, 2021, 36: 102130.
11	Kuenz A, Krull S. Biotechnological production of itaconic acid-things you have to know[J]. Applied Microbiology and Biotechnology, 2018, 102(9): 3901-3914.
12	Diankristanti P A, Effendi S S W, Hsiang C C, et al. High-level itaconic acid (IA) production using engineered Escherichia coli Lemo21(DE3) toward sustainable biorefinery[J]. Enzyme and Microbial Technology, 2023, 167: 110231.
13	Hsiang C C, Diankristanti P A, Tan S I, et al. Tailoring key enzymes for renewable and high-level itaconic acid production using genetic Escherichia coli via whole-cell bioconversion[J]. Enzyme and Microbial Technology, 2022, 160: 110087.
14	Kinoshita K. Über die produktion von itaconsäure und mannit durch einen neuen schimmelpilz Aspergillus itaconicus [J]. Acta Phytochimica, 1932, 5: 271-287.
15	Bentley R, Thiessen C P. Biosynthesis of itaconic acid in Aspergillus terreus(Ⅰ): Tracer studies with C¹⁴-labeled substrates[J]. Journal of Biological Chemistry, 1957, 226(2): 673-687.
16	Bonnarme P, Gillet B, Sepulchre A M, et al. Itaconate biosynthesis in Aspergillus terreus [J]. Journal of Bacteriology, 1995, 177(12): 3573-3578.
17	Li A, van Luijk N, ter Beek M, et al. A clone-based transcriptomics approach for the identification of genes relevant for itaconic acid production in Aspergillus [J]. Fungal Genetics and Biology, 2011, 48(6): 602-611.
18	Chen M, Huang X N, Zhong C W, et al. Identification of an itaconic acid degrading pathway in itaconic acid producing Aspergillus terreus [J]. Applied Microbiology and Biotechnology, 2016, 100(17): 7541-7548.
19	Geiser E, Przybilla S K, Friedrich A, et al. Ustilago maydis produces itaconic acid via the unusual intermediate trans-aconitate[J]. Microbial Biotechnology, 2016, 9(1): 116-126.
20	Geiser E, Hosseinpour Tehrani H, Meyer S, et al. Evolutionary freedom in the regulation of the conserved itaconate cluster by Ria1 in related Ustilaginaceae[J]. Fungal Biology and Biotechnology, 2018, 5: 14.
21	Steiger M G. Itaconic acid—an emerging building block[M]//Wierckx N, Blank L M. Industrial Biotechnology: Products and Processes. New York: John Wiley & Sons Inc., 2017: 453-472.
22	Calam C T, Oxford A E, Raistrick H. Studies in the biochemistry of micro-organisms: itaconic acid, a metabolic product of a strain of Aspergillus terreus thom[J]. Biochemical Journal, 1939, 33(9): 1488-1495.
23	Lockwood L B, Nelson G E. Some factors affecting the production of itaconic acid by Aspergillus terreus in agitated cultures[J]. Archives of Biochemistry, 1946, 10: 365-374.
24	Mario B, Schweiger L B. Process for the production of itaconic acid: US3162582[P]. 1964-12-22.
25	da Cruz J C, Camporese Sérvulo E F, de Castro A M. Microbial production of itaconic acid[M]//Microbial Production of Food Ingredients and Additives. Amsterdam: Elsevier, 2017: 291-316.
26	Hevekerl A, Kuenz A, Vorlop K D. Influence of the pH on the itaconic acid production with Aspergillus terreus [J]. Applied Microbiology and Biotechnology, 2014, 98(24): 10005-10012.
27	Krull S, Hevekerl A, Kuenz A, et al. Process development of itaconic acid production by a natural wild type strain of Aspergillus terreus to reach industrially relevant final titers[J]. Applied Microbiology and Biotechnology, 2017, 101(10): 4063-4072.
28	Mariana J, Joaquín O, Ester L M. Study of itaconic acid production by Aspergillus terrus MJL05 strain with different variable[J]. Revista Colombiana de Biotecnología, 2010, 12(2): 187.
29	Narisetty V, Prabhu A A, Al-Jaradah K, et al. Microbial itaconic acid production from starchy food waste by newly isolated thermotolerant Aspergillus terreus strain[J]. Bioresource Technology, 2021, 337: 125426.
30	Krull S, Eidt L, Hevekerl A, et al. Itaconic acid production from wheat chaff by Aspergillus terreus [J]. Process Biochemistry, 2017, 63: 169-176.
31	Kerssemakers A A J, Doménech P, Cassano M, et al. Production of itaconic acid from cellulose pulp: feedstock feasibility and process strategies for an efficient microbial performance[J]. Energies, 2020, 13(7): 1654.
32	Huang X N, Lu X F, Li Y M, et al. Improving itaconic acid production through genetic engineering of an industrial Aspergillus terreus strain[J]. Microbial Cell Factories, 2014, 13: 119.
33	Tevz G, Bencina M, Legisa M. Enhancing itaconic acid production by Aspergillus terreus [J]. Applied Microbiology and Biotechnology, 2010, 87(5): 1657-1664.
34	Shin W S, Park B, Lee D, et al. Enhanced production of itaconic acid through development of transformed fungal strains of Aspergillus terreus [J]. Journal of Microbiology and Biotechnology, 2017, 27(2): 306-315.
35	Krull S, Lünsmann M, Prüße U, et al. Ustilago rabenhorstiana—an alternative natural itaconic acid producer[J]. Fermentation, 2020, 6(1): 4.
36	Hosseinpour Tehrani H, Saur K, Tharmasothirajan A, et al. Process engineering of pH tolerant Ustilago cynodontis for efficient itaconic acid production[J]. Microbial Cell Factories, 2019, 18(1): 213.
37	Zambanini T, Hosseinpour Tehrani H, Geiser E, et al. Efficient itaconic acid production from glycerol with Ustilago vetiveriae TZ1[J]. Biotechnology for Biofuels, 2017, 10: 131.
38	Haskins R H, Thorn J A, Boothroyd B. Biochemistry of the ustilaginales(Ⅺ): Metabolic products of Ustilago zeae in submerged culture[J]. Canadian Journal of Microbiology, 1955, 1(9): 749-756.
39	Maassen N, Panakova M, Wierckx N, et al. Influence of carbon and nitrogen concentration on itaconic acid production by the smut fungus Ustilago maydis [J]. Engineering in Life Sciences, 2014, 14(2): 129-134.
40	Geiser E, Przybilla S K, Engel M, et al. Genetic and biochemical insights into the itaconate pathway of Ustilago maydis enable enhanced production[J]. Metabolic Engineering, 2016, 38: 427-435.
41	Becker J, Hosseinpour Tehrani H, Gauert M, et al. An Ustilago maydis chassis for itaconic acid production without by-products[J]. Microbial Biotechnology, 2020, 13(2): 350-362.
42	Tehrani H H, Tharmasothirajan A, Track E, et al. Engineering the morphology and metabolism of pH tolerant Ustilago cynodontis for efficient itaconic acid production[J]. Metabolic Engineering, 2019, 54: 293-300.
43	Tehrani H H, Becker J, Bator I, et al. Integrated strain-and process design enable production of 220 g·L^-1 itaconic acid with Ustilago maydis [J]. Biotechnology for Biofuels, 2019, 12(1): 263.
44	Tabuchi T, Sugisawa T, Ishidori T, et al. Itaconic acid fermentation by a yeast belonging to the genus Candida [J]. Agricultural and Biological Chemistry, 1981, 45(2): 475-479.
45	Levinson W E, Kurtzman C P, Kuo T M. Production of itaconic acid by Pseudozyma antarctica NRRL Y-7808 under nitrogen-limited growth conditions[J]. Enzyme and Microbial Technology, 2006, 39(4): 824-827.
46	Araki T, Yamazaki Y, Suzuki N. Production of itaconic acid by Helicobasidium mompa TANAKA[J]. Japanese Journal of Phytopathology, 1957, 22(2): 83-87.
47	Kautola H, Vahvaselkä M, Linko Y Y, et al. Itaconic acid production by immobilized Aspergillus terreus from xylose and glucose[J]. Biotechnology Letters, 1985, 7(3): 167-172.
48	Karaffa L, Díaz R, Papp B, et al. A deficiency of manganese ions in the presence of high sugar concentrations is the critical parameter for achieving high yields of itaconic acid by Aspergillus terreus [J]. Applied Microbiology and Biotechnology, 2015, 99(19): 7937-7944.
49	Huang X N, Chen M, Lu X F, et al. Direct production of itaconic acid from liquefied corn starch by genetically engineered Aspergillus terreus [J]. Microbial Cell Factories, 2014, 13: 108.
50	Becker J, Tehrani H H, Ernst P, et al. An optimized Ustilago maydis for itaconic acid production at maximal theoretical yield[J]. Journal of Fungi, 2020, 7(1): 20.
51	Blumhoff M L, Steiger M G, Mattanovich D, et al. Targeting enzymes to the right compartment: metabolic engineering for itaconic acid production by Aspergillus niger [J]. Metabolic Engineering, 2013, 19: 26-32.
52	Wang Y Q, Guo Y F, Cao W, et al. Synergistic effects on itaconic acid production in engineered Aspergillus niger expressing the two distinct biosynthesis clusters from Aspergillus terreus and Ustilago maydis [J]. Microbial Cell Factories, 2022, 21(1): 158.
53	Xie H, Ma Q Y, Wei D Z, et al. Metabolic engineering of an industrial Aspergillus niger strain for itaconic acid production[J]. 3 Biotech, 2020, 10(3): 113.
54	van der Straat L, Vernooij M, Lammers M, et al. Expression of the Aspergillus terreus itaconic acid biosynthesis cluster in Aspergillus niger [J]. Microbial Cell Factories, 2014, 13: 11.
55	Hossain A H, Li A, Brickwedde A, et al. Rewiring a secondary metabolite pathway towards itaconic acid production in Aspergillus niger [J]. Microbial Cell Factories, 2016, 15(1): 130.
56	Hossain A H, van Gerven R, Overkamp K M, et al. Metabolic engineering with ATP-citrate lyase and nitrogen source supplementation improves itaconic acid production in Aspergillus niger [J]. Biotechnology for Biofuels, 2019, 12: 233.
57	Blazeck J, Miller J, Pan A, et al. Metabolic engineering of Saccharomyces cerevisiae for itaconic acid production[J]. Applied Microbiology and Biotechnology, 2014, 98(19): 8155-8164.
58	Xu Y Y, Li Z M. Utilization of ethanol for itaconic acid biosynthesis by engineered Saccharomyces cerevisiae [J]. FEMS Yeast Research, 2021, 21(6): foab043.
59	Sun W, Vila-Santa A, Liu N, et al. Metabolic engineering of an acid-tolerant yeast strain Pichia kudriavzevii for itaconic acid production[J]. Metabolic Engineering Communications, 2020, 10: e00124.
60	Blazeck J, Hill A, Jamoussi M, et al. Metabolic engineering of Yarrowia lipolytica for itaconic acid production[J]. Metabolic Engineering, 2015, 32: 66-73.
61	Zhao C, Cui Z Y, Zhao X Y, et al. Enhanced itaconic acid production in Yarrowia lipolytica via heterologous expression of a mitochondrial transporter MTT[J]. Applied Microbiology and Biotechnology, 2019, 103(5): 2181-2192.
62	Rong L X, Miao L, Wang S H, et al. Engineering Yarrowia lipolytica to produce itaconic acid from waste cooking oil[J]. Frontiers in Bioengineering and Biotechnology, 2022, 10: 888869.
63	Otten A, Brocker M, Bott M. Metabolic engineering of Corynebacterium glutamicum for the production of itaconate[J]. Metabolic Engineering, 2015, 30: 156-165.
64	Merkel M, Kiefer D, Schmollack M, et al. Acetate-based production of itaconic acid with Corynebacterium glutamicum using an integrated pH-coupled feeding control[J]. Bioresource Technology, 2022, 351: 126994.
65	Okamoto S, Chin T, Hiratsuka K, et al. Production of itaconic acid using metabolically engineered Escherichia coli [J]. Journal of General and Applied Microbiology, 2014, 60(5): 191-197.
66	Jeon H G, Cheong D E, Han Y, et al. Itaconic acid production from glycerol using Escherichia coli harboring a random synonymous codon-substituted 5'-coding region variant of the cadA gene[J]. Biotechnology and Bioengineering, 2016, 113(7): 1504-1510.
67	Harder B J, Bettenbrock K, Klamt S. Model-based metabolic engineering enables high yield itaconic acid production by Escherichia coli [J]. Metabolic Engineering, 2016, 38: 29-37.
68	Harder B J, Bettenbrock K, Klamt S. Temperature-dependent dynamic control of the TCA cycle increases volumetric productivity of itaconic acid production by Escherichia coli [J]. Biotechnology and Bioengineering, 2018, 115(1): 156-164.
69	Yang Z W, Wang H L, Wang Y X, et al. Manufacturing multienzymatic complex reactors in vivo by self-assembly to improve the biosynthesis of itaconic acid in Escherichia coli [J]. ACS Synthetic Biology, 2018, 7(5): 1244-1250.
70	Zhao C, Chen S L, Fang H. Consolidated bioprocessing of lignocellulosic biomass to itaconic acid by metabolically engineering Neurospora crassa [J]. Applied Microbiology and Biotechnology, 2018, 102(22): 9577-9584.
71	Elmore J R, Dexter G N, Salvachúa D, et al. Production of itaconic acid from alkali pretreated lignin by dynamic two stage bioconversion[J]. Nature Communications, 2021, 12(1): 2261.
72	Chin T, Sano M, Takahashi T, et al. Photosynthetic production of itaconic acid in Synechocystis sp. PCC6803[J]. Journal of Biotechnology, 2015, 195: 43-45.
73	Cairns T C, Barthel L, Meyer V. Something old, something new: challenges and developments in Aspergillus niger biotechnology[J]. Essays in Biochemistry, 2021, 65(2): 213-224.
74	Li A, Pfelzer N, Zuijderwijk R, et al. Reduced by-product formation and modified oxygen availability improve itaconic acid production in Aspergillus niger [J]. Applied Microbiology and Biotechnology, 2013, 97(9): 3901-3911.
75	Porro D, Branduardi P. Production of organic acids by yeasts and filamentous fungi[M]//Sibirny A A. Biotechnology of Yeasts and Filamentous Fungi. Cham: Springer International Publishing, 2017: 205-223.
76	Beopoulos A, Nicaud J M, Gaillardin C. An overview of lipid metabolism in yeasts and its impact on biotechnological processes[J]. Applied Microbiology and Biotechnology, 2011, 90(4): 1193-1206.
77	Joo Y C, You S K, Shin S K, et al. Bio-based production of dimethyl itaconate from rice wine waste-derived itaconic acid[J]. Biotechnology Journal, 2017, 12(11): 1700114.
78	Pontrelli S, Chiu T Y, Lan E I, et al. Escherichia coli as a host for metabolic engineering[J]. Metabolic Engineering, 2018, 50: 16-46.
79	Liu H, Song R R, Liang Y, et al. Genetic manipulation of Escherichia coli central carbon metabolism for efficient production of fumaric acid[J]. Bioresource Technology, 2018, 270: 96-102.
80	de Carvalho C C C R. Whole cell biocatalysts: essential workers from nature to the industry[J]. Microbial Biotechnology, 2017, 10(2): 250-263.
81	Madavi T B, Chauhan S, Keshri A, et al. Whole-cell biocatalysis: advancements toward the biosynthesis of fuels[J]. Biofuels, Bioproducts and Biorefining, 2022, 16(3): 859-876.
82	Lin B X, Tao Y. Whole-cell biocatalysts by design[J]. Microbial Cell Factories, 2017, 16(1): 106.
83	Yang Z W, Gao X, Xie H, et al. Enhanced itaconic acid production by self-assembly of two biosynthetic enzymes in Escherichia coli [J]. Biotechnology and Bioengineering, 2017, 114(2): 457-462.
84	Kim J, Seo H M, Bhatia S K, et al. Production of itaconate by whole-cell bioconversion of citrate mediated by expression of multiple cis-aconitate decarboxylase (cadA) genes in Escherichia coli [J]. Scientific Reports, 2017, 7: 39768.
85	Feng J, Li C Q, He H, et al. Construction of cell factory through combinatorial metabolic engineering for efficient production of itaconic acid[J]. Microbial Cell Factories, 2022, 21(1): 275.
86	Zhang J, Jin B, Hong K Q, et al. Cell catalysis of citrate to itaconate by engineered Halomonas bluephagenesis [J]. ACS Synthetic Biology, 2021, 10(11): 3017-3027.
87	张静, 元跃, 王智文, 等. 基于工程化盐单胞菌TDZI-08一锅法合成衣康酸[J]. 生物工程学报, 2024, 40(8): 2666-2677.
	Zhang J, Yuan Y, Wang Z W, et al. One-pot synthesis of itaconic acid by engineered Halomonas bluephagenesis TDZI-08[J]. Chinese Journal of Biotechnology, 2024, 40(8): 2666-2677.
88	Luo G, Fujino M, Nakano S, et al. Accelerating itaconic acid production by increasing membrane permeability of whole-cell biocatalyst based on a psychrophilic bacterium Shewanella livingstonensis Ac10[J]. Journal of Biotechnology, 2020, 312: 56-62.
89	Hanko E K R, Minton N P, Malys N. A transcription factor-based biosensor for detection of itaconic acid[J]. ACS Synthetic Biology, 2018, 7(5): 1436-1446.
90	Zhao M, Li Y T, Wang F Q, et al. A CRISPRi mediated self-inducible system for dynamic regulation of TCA cycle and improvement of itaconic acid production in Escherichia coli [J]. Synthetic and Systems Biotechnology, 2022, 7(3): 982-988.
91	Okabe M, Ohta N, Park Y S. Itaconic acid production in an air-lift bioreactor using a modified draft tube[J]. Journal of Fermentation and Bioengineering, 1993, 76(2): 117-122.
92	Lin Y H, Li Y F, Huang M C, et al. Intracellular expression of Vitreoscilla hemoglobin in Aspergillus terreus to alleviate the effect of a short break in aeration during culture[J]. Biotechnology Letters, 2004, 26(13): 1067-1072.
93	Songserm P, Thitiprasert S, Tolieng V, et al. Regulating pyruvate carboxylase in the living culture of Aspergillus terreus NRRL 1960 by L-aspartate for enhanced itaconic acid production[J]. Applied Biochemistry and Biotechnology, 2015, 177(3): 595-609.
94	Li A, Pfelzer N, Zuijderwijk R, et al. Enhanced itaconic acid production in Aspergillus niger using genetic modification and medium optimization[J]. BMC Biotechnology, 2012, 12: 57.
95	Vassilev N, Kautola H, Linko Y Y. Immobilized Aspergillus terreus in itaconic acid production from glucose[J]. Biotechnology Letters, 1992, 14(3): 201-206.
96	Zhao M L, Lu X Y, Zong H, et al. Itaconic acid production in microorganisms[J]. Biotechnology Letters, 2018, 40(3): 455-464.

菌株	策略	碳源	发酵方式	产量/(g/L)	得率/(g/g)	文献
A. terreus NRRL 265	深层发酵	蔗糖	发酵罐	48.7	—	[8]
A. terreus NRRL 1960	孢子或菌丝固定化发酵	木糖和葡萄糖	摇瓶	30	0.54	[47]
A. terreus NRRL 1960	优化培养基组成包括底物和多种微量元素浓度	葡萄糖	发酵罐	91	—	[24]
A. terreus NRRL 1960	优化锰离子和葡萄糖浓度	葡萄糖	发酵罐	130	0.65	[48]
A. terreus DSM 23081	培养2.1 d后将pH控制至3	葡萄糖	发酵罐	146	0.59	[26]
A. terreus DSM 23081	将生产阶段pH提高至3.4	葡萄糖	发酵罐	160 150	0.46 0.56	[27]
A. terreus DSM 23081	麦糠进行碱性预处理，50℃、pH 4.8下用10 FPU/g_生物量 Biogazyme 2x进行酶糖化，再通过阳离子交换剂进行纯化后用于衣康酸发酵合成	麦糠	摇瓶	27.7	0.41	[30]
A. terreus NRRL 1960	纤维素浆水解液用膜过滤灭菌、碳氮比为20∶1和氧可用性为7.33 （空气体积/培养基体积）	纤维素浆水解液	摇瓶	37.5	0.62	[31]
A. terreus A156	过表达来源于Aspergillus niger的截短的pfkA	葡萄糖	摇瓶	31	—	[33]
A. terreus LYT10	过表达cadA	葡萄糖	发酵罐	78.5	0.67	[32]
A. terreus AN37	过表达本源cadA和mfsA突变体	葡萄糖	摇瓶	75	0.68	[34]
A. terreus CICC 40205	过表达A. niger来源的glaA	淀粉水解物	摇瓶	77.6	—	[49]
A. pseudoterreus ATCC32359	过表达全局调节因子LaeA	葡萄糖	摇瓶	30.4	—	[2]
U. zeae	野生型	—	—	15	—	[38]
U. maydis MB215	优化葡萄糖浓度和NH₄Cl浓度	葡萄糖	发酵罐	44.5	0.24	[39]
U. maydis MB215	敲除cyp3并利用启动子P _etef 过表达ria1	葡萄糖	发酵罐	54.8	0.48	[40]
U. maydis MB215	敲除cyp3、MEL、UA和dgat并过表达ria1	葡萄糖	摇瓶	53.5	0.47	[41]
U. maydis MB215	过表达本源rai1和mttA并敲除cyp3、fuz7、MEL、UA和dgat	葡萄糖	发酵罐	74.9	0.54	[50]
U. maydis MB215	过表达本源rai1和mttA并敲除cyp3和fuz7	葡萄糖	发酵罐	220	0.33	[43]
U. cynodontis NBRC9727	过表达本源rai1和mttA并敲除cyp3和fuz7	葡萄糖	发酵罐	22.3	0.42	[42]
Candida sp. strain B-1	野生型	葡萄糖	摇瓶	35	—	[44]
P. antarctica NRRL Y-7808	野生型	葡萄糖	摇瓶	30	0.29	[45]
P. tsukubaensis H488	野生型	葡萄糖	发酵罐	74.7	0.49	[11]
H. mompa TANAKA	野生型	甘薯	摇瓶	0.5	—	[46]

菌株	策略	碳源	发酵方式	产量/(g/L)	得率/(g/g)	文献
A. terreus NRRL 265	深层发酵	蔗糖	发酵罐	48.7	—	[8]
A. terreus NRRL 1960	孢子或菌丝固定化发酵	木糖和葡萄糖	摇瓶	30	0.54	[47]
A. terreus NRRL 1960	优化培养基组成包括底物和多种微量元素浓度	葡萄糖	发酵罐	91	—	[24]
A. terreus NRRL 1960	优化锰离子和葡萄糖浓度	葡萄糖	发酵罐	130	0.65	[48]
A. terreus DSM 23081	培养2.1 d后将pH控制至3	葡萄糖	发酵罐	146	0.59	[26]
A. terreus DSM 23081	将生产阶段pH提高至3.4	葡萄糖	发酵罐	160 150	0.46 0.56	[27]
A. terreus DSM 23081	麦糠进行碱性预处理，50℃、pH 4.8下用10 FPU/g_生物量 Biogazyme 2x进行酶糖化，再通过阳离子交换剂进行纯化后用于衣康酸发酵合成	麦糠	摇瓶	27.7	0.41	[30]
A. terreus NRRL 1960	纤维素浆水解液用膜过滤灭菌、碳氮比为20∶1和氧可用性为7.33 （空气体积/培养基体积）	纤维素浆水解液	摇瓶	37.5	0.62	[31]
A. terreus A156	过表达来源于Aspergillus niger的截短的pfkA	葡萄糖	摇瓶	31	—	[33]
A. terreus LYT10	过表达cadA	葡萄糖	发酵罐	78.5	0.67	[32]
A. terreus AN37	过表达本源cadA和mfsA突变体	葡萄糖	摇瓶	75	0.68	[34]
A. terreus CICC 40205	过表达A. niger来源的glaA	淀粉水解物	摇瓶	77.6	—	[49]
A. pseudoterreus ATCC32359	过表达全局调节因子LaeA	葡萄糖	摇瓶	30.4	—	[2]
U. zeae	野生型	—	—	15	—	[38]
U. maydis MB215	优化葡萄糖浓度和NH₄Cl浓度	葡萄糖	发酵罐	44.5	0.24	[39]
U. maydis MB215	敲除cyp3并利用启动子P _etef 过表达ria1	葡萄糖	发酵罐	54.8	0.48	[40]
U. maydis MB215	敲除cyp3、MEL、UA和dgat并过表达ria1	葡萄糖	摇瓶	53.5	0.47	[41]
U. maydis MB215	过表达本源rai1和mttA并敲除cyp3、fuz7、MEL、UA和dgat	葡萄糖	发酵罐	74.9	0.54	[50]
U. maydis MB215	过表达本源rai1和mttA并敲除cyp3和fuz7	葡萄糖	发酵罐	220	0.33	[43]
U. cynodontis NBRC9727	过表达本源rai1和mttA并敲除cyp3和fuz7	葡萄糖	发酵罐	22.3	0.42	[42]
Candida sp. strain B-1	野生型	葡萄糖	摇瓶	35	—	[44]
P. antarctica NRRL Y-7808	野生型	葡萄糖	摇瓶	30	0.29	[45]
P. tsukubaensis H488	野生型	葡萄糖	发酵罐	74.7	0.49	[11]
H. mompa TANAKA	野生型	甘薯	摇瓶	0.5	—	[46]

菌株	策略	碳源	发酵方式	产量/(g/L)	得率/(g/g)	文献
A. niger AB 1.13	过表达异源cadA	葡萄糖	摇瓶	0.7	0.01	[17]
A. niger ATCC 1015	线粒体定位表达acoA和cadA	葡萄糖	摇瓶	1.2	—	[51]
A. niger ATCC 1015	过表达mttA、mfsA、adi1、tad1、itp1、acoA并敲除ictA	葡萄糖	摇瓶	9.08	0.09	[52]
A. niger YX-1217	过表达由P _glaA 启动子调控的下肽接头连接的acoA和cadA	玉米粉	发酵罐	7.2	—	[53]
A. niger NW186	oahA和goxC突变，过表达异源cadA、mttA 和mfsA	山梨醇和木糖	发酵罐	7.1	—	[54]
A. niger AB 1.13	过表达citB、cadA、mttA和mfsA	葡萄糖	发酵罐	26.2	0.37	[55]
A. niger AB 1.13	过表达acl12、citB、cadA、mttA和mfsA	葡萄糖	发酵罐	42.7	0.26	[56]
S. cerevisiae BY4741	过表达A. terreus来源的cadA	葡萄糖	摇瓶	0.168	—	[57]
S. cerevisiae XYY27	过表达cadA、cyc1t和AAC2	乙醇	摇瓶	0.142	—	[58]
P. kudriavzevii YB4010	过表达异源cadA、本源pk和mttA并敲除icd	葡萄糖	发酵罐	1.23	0.029	[59]
Y. lipolytica PO1f	胞浆中共表达cadA和ACOnoMLS	葡萄糖	发酵罐	4.6	0.058	[60]
Y. lipolytica PO1f	过表达A. terreus来源的cadA、mttA、mfsA和acoA	葡萄糖	发酵罐	22	0.056	[61]
Y. lipolytica Po1g	过氧化物酶体中表达cadA，过表达POT1并敲除icl	废弃食用油	发酵罐	54.6	0.3	[62]
C. glutamicum	过表达cadA与MBP的融合基因；突变异柠檬酸脱氢酶基因	葡萄糖	摇瓶	7.8	0.29	[63]
C. glutamicum	过表达异源的cadA并突变icd	乙酸盐	发酵罐	29.2	0.16	[64]
E. coli BW25113	过表达异源的cadA和acnB，敲除icd	葡萄糖	摇瓶	4.34	—	[65]
E. coli XL1-Blue	过表达高可溶性表达的同义密码子变体scv_cadA	甘油	发酵罐	7.2	—	[66]
E. coli MG1655 (ita23)	过表达cadA和gltA，下调icd，敲除aceA、sucCD、pta、pykA和pykF	葡萄糖	发酵罐	32	0.43	[67]
E. coli MG1655 (ita36A)	过表达cadA和gltA，替换icd启动子为λ启动子，敲除aceA、sucCD、pta、pykA和pykF	葡萄糖	发酵罐	47	0.45	[68]
E. coli MG1655	过表达由GA、ACN和CAD组成的多酶复合体，敲除icd	葡萄糖	摇瓶	3.06	—	[69]
N. crassa FGSC9720	过表达异源的cadA	玉米秸秆	摇瓶	0.02	—	[70]
P. putida	过表达由生物传感器PurtA∶T7pol∶lysY⁺调控的cadA，敲除PHA合成酶	碱预处理木质素	摇瓶	1.3	—	[71]
Synechocystis sp. PCC6803	过表达异源的cadA	CO₂	摇瓶	0.014	—	[72]

菌株	策略	碳源	发酵方式	产量/(g/L)	得率/(g/g)	文献
A. niger AB 1.13	过表达异源cadA	葡萄糖	摇瓶	0.7	0.01	[17]
A. niger ATCC 1015	线粒体定位表达acoA和cadA	葡萄糖	摇瓶	1.2	—	[51]
A. niger ATCC 1015	过表达mttA、mfsA、adi1、tad1、itp1、acoA并敲除ictA	葡萄糖	摇瓶	9.08	0.09	[52]
A. niger YX-1217	过表达由P _glaA 启动子调控的下肽接头连接的acoA和cadA	玉米粉	发酵罐	7.2	—	[53]
A. niger NW186	oahA和goxC突变，过表达异源cadA、mttA 和mfsA	山梨醇和木糖	发酵罐	7.1	—	[54]
A. niger AB 1.13	过表达citB、cadA、mttA和mfsA	葡萄糖	发酵罐	26.2	0.37	[55]
A. niger AB 1.13	过表达acl12、citB、cadA、mttA和mfsA	葡萄糖	发酵罐	42.7	0.26	[56]
S. cerevisiae BY4741	过表达A. terreus来源的cadA	葡萄糖	摇瓶	0.168	—	[57]
S. cerevisiae XYY27	过表达cadA、cyc1t和AAC2	乙醇	摇瓶	0.142	—	[58]
P. kudriavzevii YB4010	过表达异源cadA、本源pk和mttA并敲除icd	葡萄糖	发酵罐	1.23	0.029	[59]
Y. lipolytica PO1f	胞浆中共表达cadA和ACOnoMLS	葡萄糖	发酵罐	4.6	0.058	[60]
Y. lipolytica PO1f	过表达A. terreus来源的cadA、mttA、mfsA和acoA	葡萄糖	发酵罐	22	0.056	[61]
Y. lipolytica Po1g	过氧化物酶体中表达cadA，过表达POT1并敲除icl	废弃食用油	发酵罐	54.6	0.3	[62]
C. glutamicum	过表达cadA与MBP的融合基因；突变异柠檬酸脱氢酶基因	葡萄糖	摇瓶	7.8	0.29	[63]
C. glutamicum	过表达异源的cadA并突变icd	乙酸盐	发酵罐	29.2	0.16	[64]
E. coli BW25113	过表达异源的cadA和acnB，敲除icd	葡萄糖	摇瓶	4.34	—	[65]
E. coli XL1-Blue	过表达高可溶性表达的同义密码子变体scv_cadA	甘油	发酵罐	7.2	—	[66]
E. coli MG1655 (ita23)	过表达cadA和gltA，下调icd，敲除aceA、sucCD、pta、pykA和pykF	葡萄糖	发酵罐	32	0.43	[67]
E. coli MG1655 (ita36A)	过表达cadA和gltA，替换icd启动子为λ启动子，敲除aceA、sucCD、pta、pykA和pykF	葡萄糖	发酵罐	47	0.45	[68]
E. coli MG1655	过表达由GA、ACN和CAD组成的多酶复合体，敲除icd	葡萄糖	摇瓶	3.06	—	[69]
N. crassa FGSC9720	过表达异源的cadA	玉米秸秆	摇瓶	0.02	—	[70]
P. putida	过表达由生物传感器PurtA∶T7pol∶lysY⁺调控的cadA，敲除PHA合成酶	碱预处理木质素	摇瓶	1.3	—	[71]
Synechocystis sp. PCC6803	过表达异源的cadA	CO₂	摇瓶	0.014	—	[72]

菌株	策略	产量/(g/L)	得率/(g/g)	文献
E. coli Rosetta (DE3)	过表达ACO和CAD通过蛋白肽相互作用的自组装酶	8.7	0.1	[83]
E. coli JY002	过表达acn和多拷贝cadA	41.6	0.48	[84]
E. coli BL-CAR470E-DS/A-CS	优化CAD表达并用蛋白支架共定位表达ACO和CAD	51.79	0.56	[85]
E. coli AtCg	过表达双T7启动子调控的AtCadA和CgAcnA，优化催化条件和培养基	67	0.35	[13]
E. coli Lemo21 (DE3)	过表达acn和cadA，基因组上整合表达分子伴侣基因GroESL，催化前细胞冷处理24 h	98.17	0.51	[12]
H. bluephagenesis TDZI-08	过表达cadA、acn和分子伴侣基因GroESL，增加acn表达量，弱化icd表达，优化细胞培养和催化条件	58.73	0.66	[86]
H. bluephagenesis TDZI-08	一锅法合成	40.50	0.68	[87]