Progress in the synthesis of L-threonine by metabolic engineering of Escherichia coli
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    Abstract:

    l-threonine is one of the eight essential amino acids that cannot be synthesized by the human body and must be taken from food. It is an important component of protein synthesis and is widely used in food, feed, medicine and other fields. At present, Escherichia coli can achieve a high threonine yield in fermentation, being the main bacterium used for industrial production of threonine. With the development of metabolic engineering, the modification of strains is no longer limited to mutagenesis, and the directed modification of strains greatly improves the production of l-threonine, facilitating the development of the l-threonine industry. This paper introduces the physicochemical properties and synthesis pathway of l-threonine and reviews the achievements in improving l-threonine production by metabolic engineering, aiming to enrich the knowledge about the modification of Escherichia coli for efficient synthesis of threonine.

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    [1] 华经产业研究院: 2022年全球及中国氨基酸产业规模、需求量及进出口情况分析[OL]. [2023-08-16]. https://caifuhao.eastmoney.com/news/20221126095619445727920. Hua Jing Industrial Research Institute: Analysis of global and Chinese amino acid industry scale, demand, import and export in 2022[OL]. [2023-08-16]. https://caifuhao.eastmoney.com/news/20221126095619445727920(in Chinese).
    [2] WANG J, CHENG LK, CHEN N. High-level production of l-threonine by recombinant Escherichia coli with combined feeding strategies[J]. Biotechnology, Biotechnological Equipment, 2014, 28(3): 495-501.
    [3] WANG SW, FANG Y, WANG Z, ZHANG SY, WANG LJ, GUO Y, WANG XY. Improving l-threonine production in Escherichia coli by elimination of transporters ProP and ProVWX[J]. Microbial Cell Factories, 2021, 20(1): 58.
    [4] 刘旭峰, 王宁, 郝亚男, 李英滋, 范晓光, 谢希贤. CRISPRi干扰中心代谢基因转录对苏氨酸合成的影响[J]. 食品与发酵工业, 2019, 45(8): 1-7. LIU XF, WANG N, HAO YN, LI YZ, FAN XG, XIE XX. Threonine synthesis under interfered transcriptions of genes involved in central metabolic pathway by CRISPRi[J]. Food and Fermentation Industries, 2019, 45(8): 1-7(in Chinese).
    [5] YANG Q, CAI DB, CHEN WS, CHEN HY, LUO W. Combined metabolic analyses for the biosynthesis pathway of l-threonine in Escherichia coli[J]. Frontiers in Bioengineering and Biotechnology, 2022, 10: 1010931.
    [6] GU PF, YANG F, SU TY, LI FF, LI YK, QI QS. Construction of an l-serine producing Escherichia coli via metabolic engineering[J]. Journal of Industrial Microbiology & Biotechnology, 2014, 41(9): 1443-1450.
    [7] KRUSE D, KRÄMER R, EGGELING L, RIEPING M, PFEFFERLE W, TCHIEU J, CHUNG Y, SAIER M, BURKOVSKI A. Influence of threonine exporters on threonine production in Escherichia coli[J]. Applied Microbiology and Biotechnology, 2002, 59(2): 205-210.
    [8] KIM SH, SCHNEIDER BL, REITZER L. Genetics and regulation of the major enzymes of alanine synthesis in Escherichia coli[J]. Journal of Bacteriology, 2010, 192(20): 5304-5311.
    [9] DUAN M, CHEN S, LIU XL, LIU JH, ZHU DQ. The application of Corynebacterium glutamicum in l-threonine biosynthesis[J]. Fermentation, 2023, 9(9): 822.
    [10] MCCOY RH, MEYER CE, ROSE WC. Feeding experiments with mixtures of highly purified amino acids viii. Isolation and identification of a new essential amino acid[J]. Journal of Biological Chemistry, 1935, 112: 283-302.
    [11] GONG DK, QIAO J, LI HD, LI Y, HUANG DY, WANG Z, HU XQ, WANG XY. Deleting chaperone-usher fimbriae operons to improve l-threonine production in Escherichia coli[J]. Systems Microbiology and Biomanufacturing, 2024, 4(1): 175-187.
    [12] DONG XY, QUINN PJ, WANG XY. Metabolic engineering of Escherichia coli and Corynebacterium glutamicum for the production of l-threonine[J]. Biotechnology Advances, 2011, 29(1): 11-23.
    [13] LI YJ, WEI HB, WANG T, XU QY, ZHANG CL, FAN XG, MA Q, CHEN N, XIE XX. Current status on metabolic engineering for the production of l-aspartate family amino acids and derivatives[J]. Bioresource Technology, 2017, 245(Pt B): 1588-1602.
    [14] ZHAO L, ZHANG HL, WANG XY, HAN GQ, MA WJ, HU XQ, LI Y. Transcriptomic analysis of an l-threonine-producing Escherichia coli TWF001[J]. Biotechnology and Applied Biochemistry, 2020, 67(3): 414-429.
    [15] LEE JH, LEE DE, LEE BU, KIM HS. Global analyses of transcriptomes and proteomes of a parent strain and an l-threonine-overproducing mutant strain[J]. Journal of Bacteriology, 2003, 185(18): 5442-5451.
    [16] HOLTZ WJ, KEASLING JD. Engineering static and dynamic control of synthetic pathways[J]. Cell, 2010, 140(1): 19-23.
    [17] ANESIADIS N, CLUETT WR, MAHADEVAN R. Dynamic metabolic engineering for increasing bioprocess productivity[J]. Metabolic Engineering, 2008, 10(5): 255-266.
    [18] YANG J, FANG Y, WANG JL, WANG CH, ZHAO L, WANG XY. Deletion of regulator-encoding genes fadR, fabR and iclR to increase l-threonine production in Escherichia coli[J]. Applied Microbiology and Biotechnology, 2019, 103(11): 4549-4564.
    [19] HAO RX, WANG SM, JIN X, YANG XY, QI QS, LIANG QF. Dynamic and balanced regulation of the thrABC operon gene for efficient synthesis of l-threonine[J]. Frontiers in Bioengineering and Biotechnology, 2023, 11: 1118948.
    [20] LIU JH, LI HL, XIONG H, XIE XX, CHEN N, ZHAO GR, CAIYIN Q, ZHU HJ, QIAO JJ. Two-stage carbon distribution and cofactor generation for improving l-threonine production of Escherichia coli[J]. Biotechnology and Bioengineering, 2019, 116(1): 110-120.
    [21] SUN WJ, SHI SQ, CHEN J, ZHAO W, CHEN TP, LI GX, ZHANG KJ, YU B, LIU D, CHEN Y, YING HJ, OUYANG PK. Blue light signaling regulates Escherichia coli W1688 biofilm formation and l-threonine production[J]. Microbiology Spectrum, 2022, 10(5): e0246022.
    [22] 胥健萍, 王颖, 李春, 周晓宏. 微生物细胞工厂中代谢途径动态调控策略与网络构建[J]. 化工进展, 2022, 41(12): 6511-6521. XU JP, WANG Y, LI C, ZHOU XH. Dynamic regulation strategies and regulation network construction of metabolic pathways in microbial cell factories[J]. Chemical Industry and Engineering Progress, 2022, 41(12): 6511-6521(in Chinese).
    [23] KIM YH, PARK JS, CHO JY, CHO KM, PARK YH, LEE J. Proteomic response analysis of a threonine-overproducing mutant of Escherichia coli[J]. The Biochemical Journal, 2004, 381(Pt 3): 823-829.
    [24] TSUGE Y, MATSUZAWA H. Recent progress in production of amino acid-derived chemicals using Corynebacterium glutamicum[J]. World Journal of Microbiology & Biotechnology, 2021, 37(3): 49.
    [25] KIM D, SEO SW, GAO Y, NAM H, GUZMAN GI, CHO BK, PALSSON BO. Systems assessment of transcriptional regulation on central carbon metabolism by Cra and CRP[J]. Nucleic Acids Research, 2018, 46(6): 2901-2917.
    [26] LEE KH, PARK JH, KIM TY, KIM HU, LEE SY. Systems metabolic engineering of Escherichia coli for l-threonine production[J]. Molecular Systems Biology, 2007, 3: 149.
    [27] LEE JH, SUNG BH, KIM MS, BLATTNER FR, YOON BH, KIM JH, KIM SC. Metabolic engineering of a reduced-genome strain of Escherichia coli for l-threonine production[J]. Microbial Cell Factories, 2009, 8: 2.
    [28] LIVSHITS VA, ZAKATAEVA NP, ALESHIN VV, VITUSHKINA MV. Identification and characterization of the new gene rhtA involved in threonine and homoserine efflux in Escherichia coli[J]. Research in Microbiology, 2003, 154(2): 123-135.
    [29] ZENG MX, WU H, HAN ZL, DU ZY, YU XB, LUO W. Metabolic engineering of Escherichia coli for production of 2,5-dimethylpyrazine[J]. Journal of Agricultural and Food Chemistry, 2024, 72(8): 4267-4276.
    [30] SU BL, LAI PX, DENG MR, ZHU HH. Design of a dual-responding genetic circuit for high-throughput identification of l-threonine-overproducing Escherichia coli[J]. Bioresource Technology, 2024, 395: 130407.
    [31] KANG Z, GAO CJ, WANG Q, LIU HM, QI QS. A novel strategy for succinate and polyhydroxybutyrate co-production in Escherichia coli[J]. Bioresource Technology, 2010, 101(19): 7675-7678.
    [32] WANG JL, MA WJ, FANG Y, YANG J, ZHAN J, CHEN SW, WANG XY. Increasing l-threonine production in Escherichia coli by overexpressing the gene cluster phaCAB[J]. Journal of Industrial Microbiology and Biotechnology, 2019, 46(11): 1557-1568.
    [33] DING ZX, FANG Y, ZHU LF, WANG JL, WANG XY. Deletion of arcA, iclR, and tdcC in Escherichia coli to improve l-threonine production[J]. Biotechnology and Applied Biochemistry, 2019, 66(5): 794-807.
    [34] 赵慧. 代谢工程改造大肠杆菌生产l-苏氨酸[D]. 无锡: 江南大学硕士学位论文, 2018. ZHAO H. Metabolic engineering of Escherichia coli for l-threonine production[D]. Wuxi: Master’s Thesis of Jiangnan University, 2018(in Chinese).
    [35] OGAWA-MIYATA Y, KOJIMA H, SANO K. Mutation analysis of the feedback inhibition site of aspartokinase III of Escherichia coli K-12 and its use in l-threonine production[J]. Bioscience, Biotechnology, and Biochemistry, 2001, 65(5): 1149-1154.
    [36] ZHANG YF, MENG QL, MA HW, LIU YF, CAO GQ, ZHANG XR, ZHENG P, SUN JB, ZHANG DW, JIANG WX, MA YH. Determination of key enzymes for threonine synthesis through in vitro metabolic pathway analysis[J]. Microbial Cell Factories, 2015, 14: 86.
    [37] SCHÜTZE A, BENNDORF D, PÜTTKER S, production of l-serine through a novel identified exporter combined with synthetic pathway in Corynebacterium glutamicum[J]. Microbial Cell Factories, 2020, 19(1): 115.J]. Frontiers in Microbiology, 2020, 11: 233.
    [38] de MEY M, de MAESENEIRE S, SOETAERT W, VANDAMME E. Minimizing acetate formation in E. coli fermentations[J]. Journal of Industrial Microbiology & Biotechnology, 2007, 34(11): 689-700.
    [39] DONG XY, ZHAO Y, HU JY, LI Y, WANG XY. Attenuating l-lysine production by deletion of ddh and lysE and their effect on l-threonine and l-isoleucine production in Corynebacterium glutamicum[J]. Enzyme and Microbial Technology, 2016, 93/94: 70-78.
    [40] XIE XX, LIANG Y, LIU HL, LIU Y, XU QY, ZHANG CL, CHEN N. Modification of glycolysis and its effect on the production of l-threonine in Escherichia coli[J]. Journal of Industrial Microbiology & Biotechnology, 2014, 41(6): 1007-1015.
    [41] 冯志彬, 徐庆阳, 陈宁. 代谢副产物对l-苏氨酸发酵的影响及应对措施[J]. 食品与发酵工业, 2007, 33(6): 32-36. FENG ZB, XU QY, CHEN N. The effects of byproducts on l-threonine fermentation and resolved schemes[J]. Food and Fermentation Industries, 2007, 33(6): 32-36(in Chinese).
    [42] WANG M, CHEN BQ, FANG YM, TAN TW. Cofactor engineering for more efficient production of chemicals and biofuels[J]. Biotechnology Advances, 2017, 35(8): 1032-1039.
    [43] SHEN CR, LIAO JC. Synergy as design principle for metabolic engineering of 1-propanol production in Escherichia coli[J]. Metabolic Engineering, 2013, 17: 12-22.
    [44] SATOWA D, FUJIWARA R, UCHIO S, NAKANO M, OTOMO C, HIRATA Y, MATSUMOTO T, NODA S, TANAKA T, KONDO A. Metabolic engineering of E. coli for improving mevalonate production to promote NADPH regeneration and enhance acetyl-CoA supply[J]. Biotechnology and Bioengineering, 2020, 117(7): 2153-2164.
    [45] 马倩, 夏利, 谭淼, 孙全伟, 杨蒙雅, 张颖, 陈宁. 氨基酸生产的代谢工程研究进展与发展趋势[J]. 生物工程学报, 2021, 37(5): 1677-1696. MA Q, XIA L, TAN M, SUN QW, YANG MY, ZHANG Y, CHEN N. Advances and prospects in metabolic engineering for the production of amino acids[J]. Chinese Journal of Biotechnology, 2021, 37(5): 1677-1696(in Chinese).
    [46] XU YR, LIU YF, LI FR, CAO GQ, ZHENG P, SUN JB, WEN JP, ZHANG DW. Identification of a new gene yecC involved in threonine export in Escherichia coli[J]. Fems Microbiology Letters, 2017, 364(17): fnx174.
    [47] 杨冬美, 李华, 李由然, 张梁, 丁重阳, 李赢, 顾正华, 石贵阳. 大肠杆菌TdcC、SstT和LIV-1系统缺失对胞外l-苏氨酸积累的影响[J]. 微生物学通报, 2017, 44(1): 20-29. YANG DM, LI H, LI YR, ZHANG L, DING ZY, LI Y, GU ZH, SHI GY. Effects of TdcC, SstT, and LIV-1 systems deletion of Escherichia coli on extracellular l-threonine accumulation[J]. Microbiology China, 2017, 44(1): 20-29(in Chinese).
    [48] 赵磊. 大肠杆菌l-苏氨酸生产菌代谢工程改造优化[D]. 无锡: 江南大学博士学位论文, 2020. ZHAO L. Metabolic engineering modification of an Escherichia coli l-threonine production strain[D]. Wuxi: Doctoral Dissertation of Jiangnan University, 2020(in Chinese).
    [49] QIAO J, TAN X, REN HY, WU Z, HU XQ, WANG XY. Construction of an Escherichia coli strain lacking fimbriae by deleting 64 genes and its application for efficient production of poly(3-hydroxybutyrate) and l-threonine[J]. Applied and Environmental Microbiology, 2021, 87(12): e0038121.
    [50] LI YX, HAO GX, GALVANI CD, MENG YZ, FUENTE L, HOCH HC, BURR TJ. Type I and type IV pili of Xylella fastidiosa affect twitching motility, biofilm formation and cell-cell aggregation[J]. Microbiology, 2007, 153(Pt 3): 719-726.
    [51] 于海波, 徐建中, 刘立明, 张伟国. 重组大肠杆菌全细胞催化l-苏氨酸合成2,5-二甲基吡嗪[J]. 生物工程学报, 2021, 37(1): 228-241. YU HB, XU JZ, LIU LM, ZHANG WG. Biosynthesis of 2,5-dimethylpyrazine from l-threonine by whole-cell biocatalyst of recombinant Escherichia coli[J]. Chinese Journal of Biotechnology, 2021, 37(1): 228-241(in Chinese).
    [52] 闫继爱, 张雪, 张芸, 左佃光, 陈宁, 温廷益. 利用Red同源重组技术构建产l-苏氨酸的基因工程菌[J]. 中国生物工程杂志, 2010, 30(3): 79-84. YAN JA, ZHANG X, ZHANG Y, ZUO DG, CHEN N, WEN TY. Construction of genetic engineering strains for l-threonine production by red recombination[J]. China Biotechnology, 2010, 30(3): 79-84(in Chinese).
    [53] 朱向东. 微生物发酵工艺优化研究进展[J]. 化工管理, 2019(16): 202, 205. ZHU XD. Research progress on optimization of microbial fermentation process[J]. Chemical Enterprise Management, 2019(16): 202, 205(in Chinese).
    [54] JEONG JY, KIM YJ, CHO N, SHIN D, NAM TW, RYU S, SEOK YJ. Expression of ptsG encoding the major glucose transporter is regulated by ArcA in Escherichia coli[J]. The Journal of Biological Chemistry, 2004, 279(37): 38513-38518.
    [55] SU YW, GUO QQ, WANG S, ZHANG X, WANG J. Effects of betaine supplementation on l-threonine fed-batch fermentation by Escherichia coli[J]. Bioprocess and Biosystems Engineering, 2018, 41(10): 1509-1518.
    [56] LI YJ, ZHANG DZ, CAI NY, HAN C, MAO Q, WANG T, ZHOU Q, CHEN N, XIE XX. Betaine supplementation improved l-threonine fermentation of Escherichia coli THRD by upregulating zwf (glucose-6-phosphate dehydrogenase) expression[J]. Electronic Journal of Biotechnology, 2019, 39: 67-73.
    [57] LEE MH, LEE HW, PARK JH, AHN JO, JUNG JK, HWANG YI. Improved l-threonine production of Escherichia coli mutant by optimization of culture conditions[J]. Journal of Bioscience and Bioengineering, 2006, 101(2): 127-130.
    [58] CHEN N, HUANG J, FENG ZB, YU L, XU QY, WEN TY. Optimization of fermentation conditions for the biosynthesis of l-threonine by Escherichia coli[J]. Applied Biochemistry and Biotechnology, 2009, 158(3): 595-604.
    [59] OKAMOTO K, IKEDA M. Development of an industrially stable process for l-threonine fermentation by an l-methionine-auxotrophic mutant of Escherichia coli[J]. Journal of Bioscience and Bioengineering, 2000, 89(1): 87-89.
    [60] AZZAM MM, CHEN W, XIA WG, WANG S, ZHANG YN, EL-SENOUSEY HK, ZHENG CT. The impact of Bacillus subtilis DSM32315 and l-Threonine supplementation on the amino acid composition of eggs and early post-hatch performance of ducklings[J]. Frontiers in Veterinary Science, 2023, 10: 1238070.
    [61] CHALVON-DEMERSAY T, LUISE D, le FLOC’H N, TESSERAUD S, LAMBERT W, BOSI P, TREVISI P, BEAUMONT M, CORRENT E. Functional amino acids in pigs and chickens: implication for gut health[J]. Frontiers in Veterinary Science, 2021, 8: 663727.
    [62] WANG SM, CHEN XM, JIN X, GU F, JIANG W, QI QS, LIANG QF. Creating polyploid Escherichia coli and its application in efficient l-threonine production[J]. Advanced Science, 2023, 10(31): e2302417.
    [63] ZHAO L, LU Y, YANG J, FANG Y, ZHU LF, DING ZX, WANG CH, MA WJ, HU XQ, WANG XY. Expression regulation of multiple key genes to improve l-threonine in Escherichia coli[J]. Microbial Cell Factories, 2020, 19(1): 46.
    [64] WANG SM, HAO RX, JIN X, LI XM, QI QS, LIANG QF. Dynamic regulation of transporter expression to increase l-threonine production using l-threonine biosensors[J]. Fermentation, 2022, 8(6): 250.
    [65] FANG Y, WANG JL, MA WJ, YANG J, ZHANG HL, ZHAO L, CHEN SS, ZHANG SY, HU XQ, LI Y, WANG XY. Rebalancing microbial carbon distribution for l-threonine maximization using a thermal switch system[J]. Metabolic Engineering, 2020, 61: 33-46.
    [66] ZHU LF, FANG Y, DING ZX, ZHANG SY, WANG XY. Developing an l-threonine-producing strain from wild-type Escherichia coli by modifying the glucose uptake, glyoxylate shunt, and l-threonine biosynthetic pathway[J]. Biotechnology and Applied Biochemistry, 2019, 66(6): 962-976.
    [67] 王钰, 郑平, 孙际宾. 谷氨酸棒杆菌的代谢工程使能技术研究进展[J]. 生物工程学报, 2021, 37(5): 1603-1618. WANG Y, ZHENG P, SUN JB. Recent advances in developing enabling technologies for Corynebacterium glutamicum metabolic engineering[J]. Chinese Journal of Biotechnology, 2021, 37(5): 1603-1618(in Chinese).
    [68] WANG YS, BAI YL, ZENG Q, JIANG ZY, LIU YZ, WANG XY, LIU XT, LIU CL, MIN WH. Recent advances in the metabolic engineering and physiological opportunities for microbial synthesis of l-aspartic acid family amino acids: a review[J]. International Journal of Biological Macromolecules, 2023, 253(Pt 3): 126916.
    [69] ZHANG XM, GAO YJ, CHEN ZW, XU GQ, ZHANG XJ, LI H, SHI JS, KOFFAS MAG, XU ZH. High-yield
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LUO Xiaoping, SU Buli, DENG Mingrong, XU Xiaolong, ZHU Honghui. Progress in the synthesis of L-threonine by metabolic engineering of Escherichia coli. [J]. Acta Microbiologica Sinica, 2024, 64(8): 2648-2660

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  • Received:January 31,2024
  • Revised:May 28,2024
  • Online: August 06,2024
  • Published: August 04,2024
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