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2025年4月4日 周五
首页 > 过刊浏览>2023年第50卷第10期 >4667-4680. DOI:10.13344/j.microbiol.china.230136
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大肠杆菌的耐酸机制及其改造研究进展
作者:
基金项目:

国家重点研发计划(2021YFC2104400)；国家自然科学基金(NSFC22078240)


Advances in acid-resistant mechanisms and modifications of Escherichia coli
Author:
  • HAO Xueyan

    HAO Xueyan

    Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;Frontiers Research Institude for Synthetic Biology, Tianjin University, Tianjin 300072, China
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  • LIU Mengxiao

    LIU Mengxiao

    Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;Frontiers Research Institude for Synthetic Biology, Tianjin University, Tianjin 300072, China
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  • HAN Ziyi

    HAN Ziyi

    Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;Frontiers Research Institude for Synthetic Biology, Tianjin University, Tianjin 300072, China
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  • FANG Lixia

    FANG Lixia

    Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;Frontiers Research Institude for Synthetic Biology, Tianjin University, Tianjin 300072, China
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  • CAO Yingxiu

    CAO Yingxiu

    Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;Frontiers Research Institude for Synthetic Biology, Tianjin University, Tianjin 300072, China
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  • 摘要
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    摘要:

    微生物细胞在自然环境或工业应用中经常受到酸胁迫，严重制约细胞生长性能和产物合成效率。为了在各种酸性环境中生存，耐酸细菌发展出多种保护机制来维持细胞内pH稳态，如氢离子消耗、细胞膜保护、代谢修饰等。因此，深入研究耐酸机制、改进菌株耐酸能力对于利用微生物发酵合成高附加值产品具有重要意义。作为模式微生物，大肠杆菌耐酸机制的研究较为透彻，近年来其耐酸性改造也取得了重大进展。本文主要总结了大肠杆菌的氧化或葡萄糖抑制系统(acid resistance system 1, AR1)、谷氨酸依赖型耐酸系统(acid resistance system 2, AR2)、精氨酸依赖型耐酸系统(acid resistance system 3, AR3)、赖氨酸依赖型耐酸系统(acid resistance system 4, AR4)和鸟氨酸依赖型耐酸系统(acid resistance system 5, AR5)、细胞膜保护以及生物大分子修复等方面的耐酸机制，并概述了利用传统代谢工程、全局转录工程和适应性实验室进化等方法构建大肠杆菌耐酸菌株的研究进展，同时展望了大肠杆菌耐酸机制及其改造的后续研究方向。

    Abstract:

    Microbial cells are often subjected to acid stress in natural environments or industrial applications, which severely restricts cell growth and product synthesis efficiency. In order to survive in acidic environments, acid-resistant bacteria have developed diverse protective mechanisms such as hydrogen ion consumption, membrane protection, and metabolic modification to maintain intracellular pH homeostasis. Therefore, in-depth research on acid-resistant mechanisms and improving acid resistance of strains are important for microbial biosynthesis of value-added products. As a model microorganism, Escherichia coli has been well studied regarding the acid-resistant mechanisms. In recent years, significant progress has been achieved in the research on the acid-resistant modification of E. coli. This paper reviews the acid-resistant mechanisms of E. coli in terms of oxidative or glucose-repressed system (acid resistance system 1, AR1), glutamate-dependent acid resistant system (acid resistance system 2, AR2), arginine-dependent acid resistant system (acid resistance system 3, AR3), lysine-dependent acid resistant system (acid resistance system 4, AR4), ornithine-dependent acid resistant system (acid resistance system 5, AR5), cell membrane protection, and biomolecular repair. Furthermore, we summarize the progress in constructing acid-resistant E. coli strains by metabolic engineering, global transcriptional engineering, and adaptive laboratory evolution. Finally, we discuss the subsequent research directions for further deciphering the acid-resistant mechanisms and improving acid resistance of E. coli.

    参考文献
    [1] LIN ZL, ZHANG Y, WANG JQ. Engineering of transcriptional regulators enhances microbial stress tolerance[J]. Biotechnology Advances, 2013, 31(6):986-991.
    [2] XU JN, GUO L, ZHAO N, MENG XM, ZHANG J, WANG TR, WEI XY, FAN MT. Response mechanisms to acid stress of acid-resistant bacteria and biotechnological applications in the food industry[J]. Critical Reviews in Biotechnology, 2023, 43(2):258-274.
    [3] 韩吉娜, 罗欣, 朱立贤, 张一敏, 董鹏程. 大肠埃希氏菌的诱导耐酸响应及其交叉保护作用机制研究进展[J/OL]. 食品科学, (20220715)[2023-06-05]. https://gfffgc1d129f57bb244a4hfxbwppkfn0on6n9wfgfy.eds.tju.edu.cn/kcms/detail/11.2206.TS.20220715.0954.004.html. HAN JN, LUO X, ZHU LX, ZHANG YM, DONG PC. Research Progress on the Mechanisms of Escherichia coli to Acid Tolerance Response and Cross-protection[J]. Food Science, (20220715)[2023-06-05]. https://gfffgc1d129f57bb244a4hfxbwppkfn0on6n9wfgfy.eds.tju.edu.cn/kcms/detail/11.2206.TS.20220715.0954.004.html (in Chinese).
    [4] CASTANIE-CORNET MP, PENFOUND TA, SMITH D, ELLIOTT JF, FOSTER JW. Control of acid resistance in Escherichia coli[J]. Journal of Bacteriology, 1999, 181(11):3525-3535.
    [5] FOSTER JW. Escherichia coli acid resistance:tales of an amateur acidophile[J]. Nature Reviews Microbiology, 2004, 2(11):898-907.
    [6] BAK G, HAN K, KIM D, LEE Y. Roles of rpoS-activating small RNAs in pathways leading to acid resistance of Escherichia coli[J]. MicrobiologyOpen, 2014, 3(1):15-28.
    [7] LI GT, MORIGEN, YAO Y. TorR/TorS Two-Component system resists extreme acid environment by regulating the key response factor RpoS in Escherichia coli[J]. Gene, 2022, 821:146295.
    [8] UPPAL S, MAURYA SR, HIRE RS, JAWALI N. Cyclic AMP receptor protein regulates cspE, an early cold-inducible gene, in Escherichia coli[J]. Journal of Bacteriology, 2011, 193(22):6142-6151.
    [9] RICHARD H, FOSTER JW. Escherichia coli glutamate- and arginine-dependent acid resistance systems increase internal pH and reverse transmembrane potential[J]. Journal of Bacteriology, 2004, 186(18):6032-6041.
    [10] de BIASE D, PENNACCHIETTI E. Glutamate decarboxylase-dependent acid resistance in orally acquired bacteria:function, distribution and biomedical implications of the gadBC operon[J]. Molecular Microbiology, 2012, 86(4):770-786.
    [11] LU PL, MA D, CHEN YL, GUO YY, CHEN GQ, DENG HT, SHI YG. l-glutamine provides acid resistance for Escherichia coli through enzymatic release of ammonia[J]. Cell Research, 2013, 23(5):635-644.
    [12] OPDYKE JA, KANG JG, STORZ G. GadY, a small-RNA regulator of acid response genes in Escherichia coli[J]. Journal of Bacteriology, 2004, 186(20):6698-6705.
    [13] SCHWARZ J, SCHUMACHER K, BRAMEYER S, JUNG K. Bacterial battle against acidity[J]. FEMS Microbiology Reviews, 2022, 46(6):fuac037.
    [14] KANJEE U, HOURY WA. Mechanisms of acid resistance in Escherichia coli[J]. Annual Review of Microbiology, 2013, 67:65-81.
    [15] CHARLIER D, GLANSDORFF N. Biosynthesis of arginine and polyamines[J]. EcoSal Plus, 2004, 1(1):DOI:10.1128/ecosalplus.3.6.1.10.
    [16] FANG YL, KOLMAKOVA-PARTENSKY L, MILLER C. A bacterial arginine-agmatine exchange transporter involved in extreme acid resistance[J]. Journal of Biological Chemistry, 2007, 282(1):176-182.
    [17] CASALINO M, PROSSEDA G, BARBAGALLO M, IACOBINO A, CECCARINI P, CARMELA LATELLA M, NICOLETTI M, COLONNA B. Interference of the CadC regulator in the arginine-dependent acid resistance system of Shigella and enteroinvasive E. coli[J]. International Journal of Medical Microbiology, 2010, 300(5):289-295.
    [18] MOREAU PL. The lysine decarboxylase CadA protects Escherichia coli starved of phosphate against fermentation acids[J]. Journal of Bacteriology, 2007, 189(6):2249-2261.
    [19] HANEBURGER I, FRITZ G, JURKSCHAT N, TETSCH L, EICHINGER A, SKERRA A, GERLAND U, JUNG K. Deactivation of the E. coli pH stress sensor CadC by cadaverine[J]. Journal of Molecular Biology, 2012, 424(1/2):15-27.
    [20] LINDNER E, WHITE SH. Topology, dimerization, and stability of the single-span membrane protein CadC[J]. Journal of Molecular Biology, 2014, 426(16):2942-2957.
    [21] KANJEE U, GUTSCHE I, ALEXOPOULOS E, ZHAO BY, EL BAKKOURI M, THIBAULT G, LIU KY, RAMACHANDRAN S, SNIDER J, PAI EF, HOURY WA. Linkage between the bacterial acid stress and stringent responses:the structure of the inducible lysine decarboxylase[J]. The EMBO Journal, 2011, 30(5):931-944.
    [22] KASHIWAGI K, SUZUKI T, SUZUKI F, FURUCHI T, KOBAYASHI H, IGARASHI K. Coexistence of the genes for putrescine transport protein and ornithine decarboxylase at 16 min on Escherichia coli chromosome[J]. Journal of Biological Chemistry, 1991, 266(31):20922-20927.
    [23] GOLD A, CHEN L, ZHU JJ. More than meets the eye:untargeted metabolomics and lipidomics reveal complex pathways spurred by activation of acid resistance mechanisms in Escherichia coli[J]. Journal of Proteome Research, 2022, 21(12):2958-2968.
    [24] GAO XP, XU K, AHMAD N, QIN L, LI C. Recent advances in engineering of microbial cell factories for intelligent pH regulation and tolerance[J]. Biotechnology Journal, 2021, 16(9):2100151.
    [25] WILKS JC, SLONCZEWSKI JL. pH of the cytoplasm and periplasm of Escherichia coli:rapid measurement by green fluorescent protein fluorimetry[J]. Journal of Bacteriology, 2007, 189(15):5601-5607.
    [26] ZHANG JL, BAI QY, PENG YZ, FAN J, JIN CC, CAO YX, YUAN YJ. High production of triterpenoids in Yarrowia lipolytica through manipulation of lipid components[J]. Biotechnology for Biofuels, 2020, 13(1):1-13.
    [27] XU W, MUKHERJEE S, NING Y, HSU FF, ZHANG K. Cyclopropane fatty acid synthesis affects cell shape and acid resistance in Leishmania mexicana[J]. International Journal for Parasitology, 2018, 48(3/4):245-256.
    [28] XU Y, ZHAO Z, TONG WH, DING YM, LIU B, SHI YX, WANG JC, SUN SM, LIU M, WANG YH, QI QS, XIAN M, ZHAO G. An acid-tolerance response system protecting exponentially growing Escherichia coli[J]. Nature Communications, 2020, 11:1496.
    [29] BEKHIT A, FUKAMACHI T, SAITO H, KOBAYASHI H. The role of OmpC and OmpF in acidic resistance in Escherichia coli[J]. Biological and Pharmaceutical Bulletin, 2011, 34(3):330-334.
    [30] PEREZ-RATHKE A, FAHIE MA, CHISHOLM C, LIANG J, CHEN M. Mechanism of OmpG pH-dependent gating from loop ensemble and single channel studies[J]. Journal of the American Chemical Society, 2018, 140(3):1105-1115.
    [31] van de GUCHTE M, SERROR P, CHERVAUX C, SMOKVINA T, EHRLICH SD, MAGUIN E. Stress responses in lactic acid bacteria[M]//Lactic Acid Bacteria:Genetics, Metabolism and Applications. Dordrecht:Springer Netherlands, 2002:187-216.
    [32] STRACY M, JACIUK M, UPHOFF S, KAPANIDIS AN, NOWOTNY M, SHERRATT DJ, ZAWADZKI P. Single-molecule imaging of UvrA and UvrB recruitment to DNA lesions in living Escherichia coli[J]. Nature Communications, 2016, 7:12568.
    [33] FENG X, HE CY, JIAO LX, LIANG XH, ZHAO RX, GUO YC. Analysis of differential expression proteins reveals the key pathway in response to heat stress in Alicyclobacillus acidoterrestris DSM 3922T[J]. Food Microbiology, 2019, 80:77-84.
    [34] RADICELLA JP, CLARK EA, FOX MS. Some mismatch repair activities in Escherichia coli[J]. Proceedings of the National Academy of Sciences of the United States of America, 1988, 85(24):9674-9678.
    [35] GHODKE H, PAUDEL BP, LEWIS JS, JERGIC S, GOPAL K, ROMERO ZJ, WOOD EA, WOODGATE R, COX MM, van OIJEN AM. Spatial and temporal organization of RecA in the Escherichia coli DNA-damage response[J]. eLife, 2019, 8:42761.
    [36] RIPPA V, DUILIO A, Di PASQUALE P, AMORESANO A, LANDINI P, VOLKERT MR. Preferential DNA damage prevention by the E. coli AidB gene:a new mechanism for the protection of specific genes[J]. DNA Repair, 2011, 10(9):934-941.
    [37] 朱浩, 刘楠. 分子伴侣蛋白介导的革兰阴性菌耐酸机制研究进展[J]. 中国药科大学学报, 2021, 52(2):164-170. ZHU H, LIU N. Advances in research progress on acid tolerance mechanism of Gram-negative bacteria mediated by molecular chaperone protein[J]. Journal of China Pharmaceutical University, 2021, 52(2):164-170(in Chinese).
    [38] SALMON L, STULL F, SAYLE S, CATO C, AKGÜL Ş, FOIT L, AHLSTROM LS, EISENMESSER EZ, AL-HASHIMI HM, BARDWELL JCA, HOROWITZ S. The mechanism of HdeA unfolding and chaperone activation[J]. Journal of Molecular Biology, 2018, 430(1):33-40.
    [39] FU XM, WANG Y, SHAO HQ, MA J, SONG XW, ZHANG M, CHANG ZY. DegP functions as a critical protease for bacterial acid resistance[J]. The FEBS Journal, 2018, 285(18):3525-3538.
    [40] CALLONI G, CHEN TT, SCHERMANN SM, CHANG HC, GENEVAUX P, AGOSTINI F, TARTAGLIA GG, HAYER-HARTL M, HARTL FU. DnaK functions as a central hub in the E. coli chaperone network[J]. Cell Reports, 2012, 1(3):251-264.
    [41] LI MX, ZHANG JL, BAI QY, FANG LX, SONG H, CAO YX. Non-homologous end joining-mediated insertional mutagenesis reveals a novel target for enhancing fatty alcohols production in Yarrowia lipolytica[J]. Frontiers in Microbiology, 2022, 13:898884.
    [42] CAI G, LIN ZQ, SHI SB. Development and expansion of the CRISPR/Cas9 toolboxes for powerful genome engineering in yeast[J]. Enzyme and Microbial Technology, 2022, 159:110056.
    [43] 李书廷, 洪坤强, 汪保卫, 陈聪, 陈涛, 王智文. 大肠杆菌乙酸耐受性菌株的构建及其耐受机制研究进展[J]. 微生物学通报, 2020, 47(12):4250-4259. LI ST, HONG KQ, WANG BW, CHEN C, CHEN T, WANG ZW. Advances in construction of acetic acid tolerance Escherichia coli[J]. Microbiology China, 2020, 47(12):4250-4259(in Chinese).
    [44] NEGRETE A, SHILOACH J. Constitutive expression of the sRNA GadY decreases acetate production and improves E. coli growth[J]. Microbial Cell Factories, 2015, 14:148.
    [45] AISO T, KAMIYA S, YONEZAWA H, GAMOU S. Overexpression of an antisense RNA, ArrS, increases the acid resistance of Escherichia coli[J]. Microbiology, 2014, 160(5):954-961.
    [46] GAO XX, YANG XF, LI JH, ZHANG Y, CHEN P, LIN ZL. Engineered global regulator H-NS improves the acid tolerance of E. coli[J]. Microbial Cell Factories, 2018, 17(1):1-13.
    [47] TAN ZG, BLACK W, YOON JM, SHANKS JV, JARBOE LR. Improving Escherichia coli membrane integrity and fatty acid production by expression tuning of FadL and OmpF[J]. Microbial Cell Factories, 2017, 16(1):1-15.
    [48] FANG LX, FAN J, LUO SL, CHEN YR, WANG CY, CAO YX, SONG H. Genome-scale target identification in Escherichia coli for high-titer production of free fatty acids[J]. Nature Communications, 2021, 12:4976.
    [49] YAO XR, LIU P, CHEN B, WANG XY, TAO F, LIN ZL, YANG XF. Synthetic acid stress-tolerance modules improve growth robustness and lysine productivity of industrial Escherichia coli in fermentation at low pH[J]. Microbial Cell Factories, 2022, 21(1):1-14.
    [50] WANG L, WANG X, HE ZQ, ZHOU SJ, XU L, TAN XY, XU T, LI BZ, YUAN YJ. Engineering prokaryotic regulator IrrE to enhance stress tolerance in budding yeast[J]. Biotechnology for Biofuels, 2020, 13(1):1-18.
    [51] TYO KE, ALPER HS, STEPHANOPOULOS GN. Expanding the metabolic engineering toolbox:more options to engineer cells[J]. Trends in Biotechnology, 2007, 25(3):132-137.
    [52] LUO JM, ZHU WC, CAO ST, LU ZY, ZHANG MH, SONG B, SHEN YB, WANG M. Improving biotransformation efficiency of Arthrobacter simplex by enhancement of cell stress tolerance and enzyme activity[J]. Journal of Agricultural and Food Chemistry, 2021, 69(2):704-716.
    [53] GENG HF, JIANG RR. cAMP receptor protein (CRP)-mediated resistance/tolerance in bacteria:mechanism and utilization in biotechnology[J]. Applied Microbiology and Biotechnology, 2015, 99(11):4533-4543.
    [54] BASAK S, GENG H, JIANG R. Rewiring global regulator cAMP receptor protein (CRP) to improve E.coli tolerance towards low pH[J]. Journal of Biotechnology, 2014, 173:68-75.
    [55] CHONG HQ, YEOW J, WANG I, SONG H, JIANG RR. Improving acetate tolerance of Escherichia coli by rewiring its global regulator cAMP receptor protein (CRP)[J]. PLoS One, 2013, 8(10):e77422.
    [56] BASAK S, JIANG RR. Enhancing E. coli tolerance towards oxidative stress via engineering its global regulator cAMP receptor protein (CRP)[J]. PLoS One, 2012, 7(12):e51179.
    [57] ALPER H, STEPHANOPOULOS G. Global transcription machinery engineering:a new approach for improving cellular phenotype[J]. Metabolic Engineering, 2007, 9(3):258-267.
    [58] GAO X, JIANG L, ZHU LY, XU Q, XU X, HUANG H. Tailoring of global transcription sigma D factor by random mutagenesis to improve Escherichia coli tolerance towards low-pHs[J]. Journal of Biotechnology, 2016, 224:55-63.
    [59] SANDBERG TE, SALAZAR MJ, WENG LL, PALSSON BO, FEIST AM. The emergence of adaptive laboratory evolution as an efficient tool for biological discovery and industrial biotechnology[J]. Metabolic Engineering, 2019, 56:1-16.
    [60] DU B, OLSON CA, SASTRY AV, FANG X, PHANEUF PV, CHEN K, WU MY, SZUBIN R, XU SB, GAO Y, HEFNER Y, FEIST AM, PALSSON BO. Adaptive laboratory evolution of Escherichia coli under acid stress[J]. Microbiology, 2020, 166(2):141-148.
    [61] SEONG W, HAN GH, LIM HS, BAEK JI, KIM SJ, KIM D, KIM SK, LEE H, KIM H, LEE SG, LEE DH. Adaptive laboratory evolution of Escherichia coli lacking cellular byproduct formation for enhanced acetate utilization through compensatory ATP consumption[J]. Metabolic Engineering, 2020, 62:249-259.
    [62] HUGHES BS, CULLUM AJ, BENNETT AF. Evolutionary adaptation to environmental pH in experimental lineages of Escherichia coli[J]. Evolution, 2007, 61(7):1725-1734.
    [63] HARDEN MM, HE A, CREAMER K, CLARK MW, HAMDALLAH I, MARTINEZ KA 2nd, KRESSLEIN RL, BUSH SP, SLONCZEWSKI JL. Acid-adapted strains of Escherichia coli K-12 obtained by experimental evolution[J]. Applied and Environmental Microbiology, 2015, 81(6):1932-1941.
    [64] DRAGOSITS M, MOZHAYSKIY V, QUINONES- SOTO S, PARK J, TAGKOPOULOS I. Evolutionary potential, cross-stress behavior and the genetic basis of acquired stress resistance in Escherichia coli[J]. Molecular Systems Biology, 2013, 9:643.
    [65] YANG JH, ZHANG J, ZHU ZM, JIANG XY, ZHENG TF, DU GC. Revealing novel synergistic defense and acid tolerant performance of Escherichia coli in response to organic acid stimulation[J]. Applied Microbiology and Biotechnology, 2022, 106(22):7577-7594.
    [66] YANG JH, PENG Z, ZHU Q, ZHANG J, DU GC.[NiFe] Hydrogenase accessory proteins HypB-HypC accelerate proton conversion to enhance the acid resistance and d-lactic acid production of Escherichia coli[J]. ACS Synthetic Biology, 2022, 11(4):1521-1530.
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郝雪雁,刘梦晓,韩紫依,房立霞,曹英秀. 大肠杆菌的耐酸机制及其改造研究进展[J]. 微生物学通报, 2023, 50(10): 4667-4680

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  • 收稿日期:2023-02-21
  • 录用日期:2023-04-13
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