中国农业科技导报 ›› 2025, Vol. 27 ›› Issue (1): 25-34.DOI: 10.13304/j.nykjdb.2023.0244
收稿日期:
2023-03-30
接受日期:
2023-08-25
出版日期:
2025-01-15
发布日期:
2025-01-21
通讯作者:
张蕾
作者简介:
冯哲瀚 E-mail: 995494773@qq.com;
Zhehan FENG(), Deping HUA, Xuefeng MEI, Baiping ZHAO, Lei ZHANG(
)
Received:
2023-03-30
Accepted:
2023-08-25
Online:
2025-01-15
Published:
2025-01-21
Contact:
Lei ZHANG
摘要:
乳酸乳球菌是乳酸菌在异源表达蛋白方面的应用与研究中的一种重要模式菌,由于其公认的安全性、益生特性、无包涵体和内毒素、易于表面显示和细胞外分泌使其成为蛋白异源表达的理想宿主。由于乳酸乳球菌刺激黏膜免疫的特性,其在递呈病毒、细菌抗原等方面得到了广泛应用。阐述了乳酸乳球菌表达系统的相关研究进展,着重介绍了乳酸乳球菌表达异源蛋白的分泌和锚定策略,并总结了对乳酸乳球菌作为细胞工厂在食品、医药,特别是抗原呈递方面的应用,最后对乳酸乳球菌表达系统未来的研究方向进行了展望。
中图分类号:
冯哲瀚, 华德平, 梅雪锋, 赵柏萍, 张蕾. 乳酸乳球菌表达系统的研究进展及其应用[J]. 中国农业科技导报, 2025, 27(1): 25-34.
Zhehan FENG, Deping HUA, Xuefeng MEI, Baiping ZHAO, Lei ZHANG. Research Progress and Application of Lactococcus lactis Expression System[J]. Journal of Agricultural Science and Technology, 2025, 27(1): 25-34.
启动子 Promoter | 蛋白质 Protein | 来源 Origin | 宿主 Strain | 参考文献 Reference |
---|---|---|---|---|
P PTS-IIC | 绿色荧光蛋白mut3a Green fluorescent protein mut3a | 水晶果冻水母 Aequoreavictoria | NZ3900 | [ |
P32 | 草酸脱羧酶 Oxalate decarboxylase | 枯草芽孢杆菌 Bacillus subtilis | MG1363 | [ |
P44 | 脂肪酶 Lipase | 猪葡萄球菌 Staphylococcus hyicus | NZ9000 | [ |
P32 | 细菌素肠霉素P Bacteriocins enterocin P | 粪肠球菌P13 Enterococcus faecium P13 | NZ9000 | [ |
P tuf | 白细胞介素-6 Interleukin-6 | 小鼠 | IL1403 | [ |
P23 | Nicotinamide mononucleotide | 土拉弗朗西斯菌 Francisella tularensis | NZ9000 | [ |
P59 | 病毒抗原蛋白 VP2 Virus antigen protein VP2 | 传染性法氏囊病病毒 Infectious bursal disease virus | MG1363 | [ |
P59 | 葡萄球菌核酸酶 Staphylococcal nuclease | 金黄色葡萄球菌 Staphylococcus aureus | MG1363 | [ |
P23 | 溶血素O Listeriolysin O | 李斯特菌 Listeria monocytogenes | MG1363 | [ |
P1 | 脲酶亚基B Urease subunit B | 幽门螺杆菌 Helicobacter pylori | MG1363 | [ |
表1 组成型启动子调控表达异源蛋白
Table 1 Constitutive promoters regulate the expression of heterologous protein
启动子 Promoter | 蛋白质 Protein | 来源 Origin | 宿主 Strain | 参考文献 Reference |
---|---|---|---|---|
P PTS-IIC | 绿色荧光蛋白mut3a Green fluorescent protein mut3a | 水晶果冻水母 Aequoreavictoria | NZ3900 | [ |
P32 | 草酸脱羧酶 Oxalate decarboxylase | 枯草芽孢杆菌 Bacillus subtilis | MG1363 | [ |
P44 | 脂肪酶 Lipase | 猪葡萄球菌 Staphylococcus hyicus | NZ9000 | [ |
P32 | 细菌素肠霉素P Bacteriocins enterocin P | 粪肠球菌P13 Enterococcus faecium P13 | NZ9000 | [ |
P tuf | 白细胞介素-6 Interleukin-6 | 小鼠 | IL1403 | [ |
P23 | Nicotinamide mononucleotide | 土拉弗朗西斯菌 Francisella tularensis | NZ9000 | [ |
P59 | 病毒抗原蛋白 VP2 Virus antigen protein VP2 | 传染性法氏囊病病毒 Infectious bursal disease virus | MG1363 | [ |
P59 | 葡萄球菌核酸酶 Staphylococcal nuclease | 金黄色葡萄球菌 Staphylococcus aureus | MG1363 | [ |
P23 | 溶血素O Listeriolysin O | 李斯特菌 Listeria monocytogenes | MG1363 | [ |
P1 | 脲酶亚基B Urease subunit B | 幽门螺杆菌 Helicobacter pylori | MG1363 | [ |
名称 Name | 功能/应用 Function/ | 参考文献 Reference |
---|---|---|
丙氨酸 Alanine | 甜味剂 Sweetener | [ |
胆盐水解酶 Bile salt hydrolase | 肠道代谢 Intestinal metabolism | [ |
β-倍半水芹烯 β-sesquiphellandrene | 抗菌、抗氧化、抗癌 Antimicrobial, antioxidant, anticancer | [ |
芳樟醇 Linalool | 调味料 Flavouring | [ |
叶酸 Folate | 保健品 Health supplements | [ |
透明质酸 Hyaluronic acid | 化妆品、医疗 Cosmetics, medical | [ |
细菌素 Bacteriocin | 防腐剂 Preservative | [ |
植物甜蛋白马宾灵 Mabinlin | 甜味剂 Sweetener | [ |
倍半萜合酶 Sesquiterpene synthase | 代谢工程 Metabolic engineering | [ |
β-环糊精葡聚糖转移酶 β-cyclodextrin glucanotransferase | 淀粉降解 Starch degradation | [ |
香豆酸CoA连接酶 Coumarate CoA ligase | 代谢工程 Metabolic engineering | [ |
乳酸链球菌素 Nisin | 食品防腐剂 Food preservative | [ |
甜味蛋白 Brazzein | 甜味剂 Sweetener | [ |
核黄素(维生素B12) Riboflavin | 保健品 Health supplements | [ |
醇酰基转移酶 Alcohol acyltransferase | 代谢工程 Alcohol acyltransferase | [ |
白介素‑6 Interleukin-6 | 佐剂、辅药 Adjuvant | [ |
白介素‑12 Interleukin-12 | 辅药、I型过敏反应 Adjuvant,hypersensitivity type I | [ |
转化生长因子β1 Transforming growth factor beta 1 | 炎症性肠病 Inflammatory bowel disease | [ |
花生过敏原 Peanut allergen | I型过敏反应 Hypersensitivity type I | [ |
表2 乳酸乳球菌生产的工业酶、化合物和药物
Table 2 Industrial enzymes and compounds produced by L. lactis
名称 Name | 功能/应用 Function/ | 参考文献 Reference |
---|---|---|
丙氨酸 Alanine | 甜味剂 Sweetener | [ |
胆盐水解酶 Bile salt hydrolase | 肠道代谢 Intestinal metabolism | [ |
β-倍半水芹烯 β-sesquiphellandrene | 抗菌、抗氧化、抗癌 Antimicrobial, antioxidant, anticancer | [ |
芳樟醇 Linalool | 调味料 Flavouring | [ |
叶酸 Folate | 保健品 Health supplements | [ |
透明质酸 Hyaluronic acid | 化妆品、医疗 Cosmetics, medical | [ |
细菌素 Bacteriocin | 防腐剂 Preservative | [ |
植物甜蛋白马宾灵 Mabinlin | 甜味剂 Sweetener | [ |
倍半萜合酶 Sesquiterpene synthase | 代谢工程 Metabolic engineering | [ |
β-环糊精葡聚糖转移酶 β-cyclodextrin glucanotransferase | 淀粉降解 Starch degradation | [ |
香豆酸CoA连接酶 Coumarate CoA ligase | 代谢工程 Metabolic engineering | [ |
乳酸链球菌素 Nisin | 食品防腐剂 Food preservative | [ |
甜味蛋白 Brazzein | 甜味剂 Sweetener | [ |
核黄素(维生素B12) Riboflavin | 保健品 Health supplements | [ |
醇酰基转移酶 Alcohol acyltransferase | 代谢工程 Alcohol acyltransferase | [ |
白介素‑6 Interleukin-6 | 佐剂、辅药 Adjuvant | [ |
白介素‑12 Interleukin-12 | 辅药、I型过敏反应 Adjuvant,hypersensitivity type I | [ |
转化生长因子β1 Transforming growth factor beta 1 | 炎症性肠病 Inflammatory bowel disease | [ |
花生过敏原 Peanut allergen | I型过敏反应 Hypersensitivity type I | [ |
疾病 Disease | 抗原/细胞因子 Antigen/cytokine | 乳酸乳球菌菌株 Strain | 参考文献 Reference |
---|---|---|---|
肺结核 Tubercolosis | 结核分枝杆菌ESAT-6 Mycobacterial ESAT-6 antigen | MG1363 | [ |
志贺菌病 Shigella dysenteriae | 外膜蛋白A Outer membrane protein A | NZ9000 | [ |
炎症性肠病 Inflammatory bowel disease | 热休克蛋白65 Heat shock protein 65 | NCDO2118 | [ |
肠道粘膜炎 Intestinal mucositis | 胰腺炎相关蛋白I Pancreatitis-associated protein I | NZ9000 | [ |
猪链球菌感染 Streptococcus iniae infection | 猪链球菌M样蛋白 S. iniae M-like protein antigen | BFE920 | [ |
Ⅰ型糖尿病 Type Ⅰ diabetes mellitus | 葡萄球菌核酸酶 Staphylococcal nuclease | NZ9000 | [ |
囊虫病 Cysticercosis | 猪带绦虫TSOL18基因 Taenia solium TSOL18 antigen | MG1363 | [ |
幽门螺杆菌 Helicobacter pylori | 幽门螺杆菌HpaA蛋白 Helicobacter pylori HpaA | NZ3900 | [ |
传染性法氏囊病病毒 Infectious bursal disease virus | 病毒衣壳蛋白(VP2) Antigen (VP2) | NZ3900 | [ |
奇异变形杆菌感染 Proteus mirabilis infection | 奇异变形杆菌外膜蛋白A OmpA of P. mirabilis | NZ3900 | [ |
百日咳 Bordetella pertussis infection | F1S1融合蛋白 F1S1 fusion protein | NZ3900 | [ |
猪流行性腹泻病毒(PEDV) Porcine epidemic diarrhea virus (PEDV) | 猪流行性腹泻病毒s1基因 Porcine epidemic diarrhea virus S1 Gene | NZ3900 | [ |
鸭甲型肝炎病毒(DHAV) Duck hepatitis A virus (DHAV) | DHAV-3的VP1蛋白 VP1 protein of DHAV type 3 | NZ3900 | [ |
空肠弯曲杆菌感染 Campylobacter jejuni infection | cjaA基因 cjaA gene | NZ3900 | [ |
表3 乳酸乳球菌表达抗原的实际应用
Table 3 Practical application of different antigens expressed by L. lactis
疾病 Disease | 抗原/细胞因子 Antigen/cytokine | 乳酸乳球菌菌株 Strain | 参考文献 Reference |
---|---|---|---|
肺结核 Tubercolosis | 结核分枝杆菌ESAT-6 Mycobacterial ESAT-6 antigen | MG1363 | [ |
志贺菌病 Shigella dysenteriae | 外膜蛋白A Outer membrane protein A | NZ9000 | [ |
炎症性肠病 Inflammatory bowel disease | 热休克蛋白65 Heat shock protein 65 | NCDO2118 | [ |
肠道粘膜炎 Intestinal mucositis | 胰腺炎相关蛋白I Pancreatitis-associated protein I | NZ9000 | [ |
猪链球菌感染 Streptococcus iniae infection | 猪链球菌M样蛋白 S. iniae M-like protein antigen | BFE920 | [ |
Ⅰ型糖尿病 Type Ⅰ diabetes mellitus | 葡萄球菌核酸酶 Staphylococcal nuclease | NZ9000 | [ |
囊虫病 Cysticercosis | 猪带绦虫TSOL18基因 Taenia solium TSOL18 antigen | MG1363 | [ |
幽门螺杆菌 Helicobacter pylori | 幽门螺杆菌HpaA蛋白 Helicobacter pylori HpaA | NZ3900 | [ |
传染性法氏囊病病毒 Infectious bursal disease virus | 病毒衣壳蛋白(VP2) Antigen (VP2) | NZ3900 | [ |
奇异变形杆菌感染 Proteus mirabilis infection | 奇异变形杆菌外膜蛋白A OmpA of P. mirabilis | NZ3900 | [ |
百日咳 Bordetella pertussis infection | F1S1融合蛋白 F1S1 fusion protein | NZ3900 | [ |
猪流行性腹泻病毒(PEDV) Porcine epidemic diarrhea virus (PEDV) | 猪流行性腹泻病毒s1基因 Porcine epidemic diarrhea virus S1 Gene | NZ3900 | [ |
鸭甲型肝炎病毒(DHAV) Duck hepatitis A virus (DHAV) | DHAV-3的VP1蛋白 VP1 protein of DHAV type 3 | NZ3900 | [ |
空肠弯曲杆菌感染 Campylobacter jejuni infection | cjaA基因 cjaA gene | NZ3900 | [ |
1 | DUWAT P, SOURICE S, CESSELIN B, et al.. Respiration capacity of the fermenting bacterium Lactococcus lactis and its positive effects on growth and survival [J]. J. Bacteriol., 2001, 183(15):4509-4516. |
2 | SONG A A, IN L L A, LIM S H E, et al.. A review on Lactococcus lactis: from food to factory [J/OL]. Microb. Cell Fact., 2017, 16(1): 55 [2023-02-22]. . |
3 | 高莹, 李淼, 孙元, 等. 乳酸乳球菌表达系统的发展现状与前景展望[J]. 微生物学报, 2022, 62(3): 895-905. |
GAO Y, LI M, SUN Y, et al.. Development and prospects of Lactococcus lactis expression system [J]. Acta Microbiol. Sin., 2022, 62(3): 895-905. | |
4 | SRIRAMAN K, JAYARAMAN G. HtrA is essential for efficient secretion of recombinant proteins by Lactococcus lactis [J]. Appl. Environ. Microbiol., 2008, 74(23): 7442-7446. |
5 | LE LOIR Y, AZEVEDO V, OLIVEIRA S C, et al.. Protein secretion in Lactococcus lactis : an efficient way to increase the overall heterologous protein production [J/OL]. Microb. Cell Fact., 2005, 4(1): 2 [2023-02-22]. . |
6 | MCCRACKEN A, TURNER M S, GIFFARD P, et al.. Analysis of promoter sequences from Lactobacillus and Lactococcus and their activity in several Lactobacillus species [J]. Arch. Microbiol., 2000, 173(5-6): 383-389. |
7 | JENSEN P R, HAMMER K. Artificial promoters for metabolic optimization [J]. Biotechnol. Bioeng., 1998, 58(2-3): 191-195. |
8 | RUD I, JENSEN P R, NATERSTAD K, et al.. A synthetic promoter library for constitutive gene expression in Lactobacillus plantarum [J]. Microbiology (Reading), 2006, 152(Pt4): 1011-1019. |
9 | KIM E B, PIAO DA C, SON J S, et al.. Cloning and characterization of a novel tuf promoter from Lactococcus lactis subsp. lactis IL1403 [J]. Curr. Microbiol., 2009, 59(4): 425-431. |
10 | OGAUGWU C E, CHENG Q, FIECK A, et al.. Characterization of a Lactococcus lactis promoter for heterologous protein production [J]. Biotechnol. Rep. (Amst), 2018, 17: 86-92. |
11 | ZHAO C M, YANG H, ZHU X J, et al.. Oxalate-degrading enzyme recombined lactic acid bacteria strains reduce hyperoxaluria [J]. Urology, 2018, 113: 253.e1-253.e7. |
12 | DROUAULT S, ANBA J, BONNEAU S, et al.. The peptidyl-prolyl isomerase motif is lacking in PmpA, the PrsA-like protein involved in the secretion machinery of Lactococcus lactis [J]. Appl. Environ. Microbiol., 2002, 68(8): 3932-3942. |
13 | BORRERO J, JIMENEZ J J, GUTIEZ L, et al.. Use of the usp45 lactococcal secretion signal sequence to drive the secretion and functional expression of enterococcal bacteriocins in Lactococcus lactis [J]. Appl. Microbiol. Biotechnol., 2011, 89(1): 131-143. |
14 | LI H S, PIAO D C, JIANG T, et al.. Recombinant interleukin 6 with M cell-targeting moiety produced in Lactococcus lactis IL1403 as a potent mucosal adjuvant for peroral immunization [J]. Vaccine, 2015, 33(16): 1959-1967. |
15 | KONG L H, LIU T Y, YAO Q S, et al.. Enhancing the biosynthesis of nicotinamide mononucleotide in Lactococcus lactis by heterologous expression of FtnadE [J]. J. Sci. Food Agric., 2023, 103(1): 450-456. |
16 | DIEYE Y, HOEKMAN A J, CLIER F, et al.. Ability of Lactococcus lactis to export viral capsid antigens: a crucial step for development of live vaccines [J]. Appl. Environ. Microbiol., 2003, 69(12): 7281-7288. |
17 | DIEYE Y, USAI S, CLIER F, et al.. Design of a protein-targeting system for lactic acid bacteria [J]. J. Bacteriol., 2001, 183(14): 4157-4166. |
18 | BAHEY-EL-DIN M, CASEY P G, GRIFFIN B T, et al.. Efficacy of a Lactococcus lactis DeltapyrG vaccine delivery platform expressing chromosomally integrated hly from Listeria monocytogenes [J]. Bioeng. Bugs, 2010, 1(1): 66-74. |
19 | LEE M H, ROUSSEL Y, WILKS M, et al.. Expression of Helicobacter pylori urease subunit B gene in Lactococcus lactis MG1363 and its use as a vaccine delivery system against H. pylori infection in mice [J]. Vaccine, 2001, 19(28-29): 3927-3935. |
20 | GUO T, HU S, KONG J. Functional analysis and randomization of the nisin-inducible promoter for tuning gene expression in Lactococcus lactis [J]. Curr. Microbiol., 2013, 66(6): 548-554. |
21 | KUIPERS O P, BEERTHUYZEN M M, DE RUYTER P G, et al.. Autoregulation of nisin biosynthesis in Lactococcus lactis by signal transduction [J]. J. Biol. Chem., 1995, 270(45): 27299-27304. |
22 | MORELLO E, BERMÚDEZ-HUMARÁN L G, LLULL D, et al.. Lactococcus lactis, an efficient cell factory for recombinant protein production and secretion [J]. J. Mol. Microbiol. Biotechnol., 2008, 14(1-3): 48-58. |
23 | LLULL D, POQUET I. New expression system tightly controlled by zinc availability in Lactococcus lactis [J]. Appl. Environ. Microbiol., 2004, 70(9): 5398-5406. |
24 | JØRGENSEN C M, VRANG A, MADSEN S M. Recombinant protein expression in Lactococcus lactis using the P170 expression system [J]. FEMS Microbiol. Lett., 2014, 351(2): 170-178. |
25 | TANHAEIAN A, MIRZAII M, PIRKHEZRANIAN Z, et al.. Generation of an engineered food-grade Lactococcus lactis strain for production of an antimicrobial peptide: in vitro and in silico evaluation [J/OL]. BMC Biotechnol., 2020, 20(1): 19 [2023-02-22]. . |
26 | BENBOUZIANE B, RIBELLES P, AUBRY C, et al.. Development of a stress-inducible controlled expression (SICE) system in Lactococcus lactis for the production and delivery of therapeutic molecules at mucosal surfaces [J]. J. Biotechnol., 2013, 168(2): 120-129. |
27 | SCHNEEWIND O, MISSIAKAS D M. Protein secretion and surface display in gram-positive bacteria [J]. Philos. Trans. R. Soc. Lond B Biol. Sci., 2012, 367(1592): 1123-1139. |
28 | POQUET I, SAINT V, SEZNEC E, et al.. HtrA is the unique surface housekeeping protease in Lactococcus lactis and is required for natural protein processing [J]. Mol. Microbiol., 2000, 35(5): 1042-1051. |
29 | DESVAUX M, HÉBRAUD M, TALON R, et al.. Secretion and subcellular localizations of bacterial proteins: a semantic awareness issue [J]. Trends Microbiol., 2009, 17(4): 139-145. |
30 | NG D T, SARKAR C A. Engineering signal peptides for enhanced protein secretion from Lactococcus lactis [J]. Appl. Environ. Microbiol., 2013, 79(1): 347-356. |
31 | BARADARAN A, SIEO C C, FOO H L, et al.. Cloning and in silico characterization of two signal peptides from Pediococcus pentosaceus and their function for the secretion of heterologous protein in Lactococcus lactis [J]. Biotechnol. Lett., 2013, 35(2): 233-238. |
32 | SUBRAMANIAM M, BARADARAN A, ROSLI M I, et al.. Effect of signal peptides on the secretion of β-cyclodextrin glucanotransferase in Lactococcus lactis NZ9000 [J]. J. Mol. Microbiol. Biotechnol., 2012, 22(6): 361-372. |
33 | NEEF J, KOEDIJK D G, BOSMA T, et al.. Efficient production of secreted staphylococcal antigens in a non-lysing and proteolytically reduced Lactococcus lactis strain [J]. Appl. Microbiol. Biotechnol., 2014, 98(24): 10131-10141. |
34 | VAN DIJL J M, HECKER M. Bacillus subtilis: from soil bacterium to super-secreting cell factory [J/OL]. Microb. Cell Fact., 2013, 12:3 [2023-02-22]. . |
35 | YOSHIDA K, VAN DIJL J M. Engineering Bacillus subtilis cells as factories: enzyme secretion and value-added chemical production [J]. Biotechnol. Bioprocess Eng., 2020, 25(6): 872-885. |
36 | SAMAZAN F, ROKBI B, SEGUIN D, et al.. Production, secretion and purification of a correctly folded staphylococcal antigen in Lactococcus lactis [J/OL]. Microb. Cell Fact., 2015, 14:104 [2023-02-22]. . |
37 | BERMÚDEZ-HUMARÁN L G, MOTTA J P, AUBRY C, et al.. Serine protease inhibitors protect better than IL-10 and TGF-β anti-inflammatory cytokines against mouse colitis when delivered by recombinant lactococci [J/OL]. Microb. Cell Fact., 2015, 14: 26 [2023-02-22]. . |
38 | TRÉMILLON N, ISSALY N, MOZO J, et al.. Production and purification of staphylococcal nuclease in Lactococcus lactis using a new expression-secretion system and a pH-regulated mini-reactor [J/OL]. Microb. Cell Fact., 2010, 9(1): 37 [2023-02-22]. . |
39 | LEENHOUTS K, BUIST G, KOK J. Anchoring of proteins to lactic acid bacteria [J]. Antonie Van Leeuwenhoek, 1999, 76(1-4): 367-376. |
40 | MAZMANIAN S K, LIU G, TON-THAT H, et al.. Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall [J]. Science, 1999, 285(5428): 760-763. |
41 | NAVARRE W W, SCHNEEWIND O. Proteolytic cleavage and cell wall anchoring at the LPXTG motif of surface proteins in gram-positive bacteria [J]. Mol. Microbiol., 1994, 14(1): 115-121. |
42 | BERLEC A, ZADRAVEC P, JEVNIKAR Z, et al.. Identification of candidate carrier proteins for surface display on Lactococcus lactis by theoretical and experimental analyses of the surface proteome [J]. Appl. Environ. Microbiol., 2011, 77(4): 1292-1300. |
43 | VAN ROOSMALEN M L, KANNINGA R, KHATTABI M E L, et al.. Mucosal vaccine delivery of antigens tightly bound to an adjuvant particle made from food-grade bacteria [J]. Methods, 2006, 38(2): 144-149. |
44 | BARADARAN A, YUSOFF K, SHAFEE N, et al.. Newcastle disease virus hemagglutinin neuraminidase as a potential cancer targeting agent [J]. J. Cancer, 2016, 7(4): 462-466. |
45 | KALYANASUNDRAM J, CHIA S L, SONG A A, et al.. Surface display of glycosylated Tyrosinase related protein-2 (TRP-2) tumour antigen on Lactococcus lactis [J/OL]. BMC Biotechnol., 2015, 15:113 [2023-02-22]. . |
46 | HOLS P, KLEEREBEZEM M, SCHANCK A N, et al.. Conversion of Lactococcus lactis from homolactic to homoalanine fermentation through metabolic engineering [J]. Nat. Biotechnol., 1999, 17(6): 588-592. |
47 | DONG Z, ZHANG J, LI H, et al.. Codon and propeptide optimizations to improve the food-grade expression of bile salt hydrolase in Lactococcus lactis [J]. Protein Pept. Lett., 2015, 22(8): 727-735. |
48 | SONG A A, ABDULLAH J O, ABDULLAH M P, et al.. Overexpressing 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) in the lactococcal mevalonate pathway for heterologous plant sesquiterpene production [J/OL]. PLoS One, 2012, 7(12): e52444 [2023-02-22]. . |
49 | HERNÁNDEZ I, MOLENAAR D, BEEKWILDER J, et al.. Expression of plant flavor genes in Lactococcus lactis [J]. Appl. Environ. Microbiol., 2007, 73(5): 1544-1552. |
50 | SYBESMA W, BURGESS C, STARRENBURG M, et al.. Multivitamin production in Lactococcus lactis using metabolic engineering [J]. Metab. Eng., 2004, 6(2): 109-115. |
51 | RAJENDRAN V, PUVENDRAN K, GURU B, et al. Design of aqueous two-phase systems for purification of hyaluronic acid produced by metabolically engineered Lactococcus lactis [J]. J. Sep. Sci., 2016, 39(4):655-662. |
52 | ÜNLÜ G, NIELSEN B, IONITA C. Inhibition of Listeria monocytogenes in hot dogs by surface application of freeze-dried bacteriocin-containing powders from lactic acid bacteria [J]. Probiotics Antimicro. Prot., 2016, 8(2): 102-110. |
53 | GU W, XIA Q, YAO J, et al.. Recombinant expressions of sweet plant protein mabinlin II in Escherichia coli and food-grade Lactococcus lactis [J]. World J. Microbiol. Biotechnol., 2015, 31(4): 557-567. |
54 | SONG A A L, ABDULLAH J O, ABDULLAH M P, et al.. Functional expression of an orchid fragrance gene in Lactococcus lactis [J]. Int. J. Mol. Sci., 2012, 13(2): 1582-1597. |
55 | MARTíNEZ-CUESTA M C, GASSON M J, NARBAD A. Heterologous expression of the plant coumarate: CoA ligase in Lactococcus lactis [J]. Lett. Appl. Microbiol., 2005, 40(1): 44-49. |
56 | ZHANG X J, FENG S Y, LI Z T, et al.. Expression of Helicobacter pylori hspA gene in Lactococcus lactis NICE system and experimental study on its immunoreactivity [J/OL]. Gastroenterol. Res. Pract., 2015, 2015:750932 [2023-02-22]. . |
57 | BERLEC A, RAVNIKAR M, STRUKELJ B. Lactic acid bacteria as oral delivery systems for biomolecules [J]. Pharmazie, 2012, 67(11): 891-898. |
58 | SYBESMA W, VAN DEN BORN E, STARRENBURG M, et al.. Controlled modulation of folate polyglutamyl tail length by metabolic engineering of Lactococcus lactis [J]. Appl. Environ. Microbiol., 2003, 69(12): 7101-7107. |
59 | STEIDLER L, HANS W, SCHOTTE L, et al.. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10 [J]. Science, 2000, 289(5483): 1352-1355. |
60 | GLENTING J, POULSEN L K, KATO K, et al.. Production of recombinant peanut allergen Ara h 2 using Lactococcus lactis [J/OL]. Microb. Cell Fact., 2007, 6:28 [2023-02-22]. . |
61 | POUWELS P H, LEER R J, SHAW M, et al.. Lactic acid bacteria as antigen delivery vehicles for oral immunization purposes [J]. Int. J. Food Microbiol., 1998, 41(2): 155-167. |
62 | DUARTE S O D, MONTEIRO G A. Plasmid replicons for the production of pharmaceutical-grade pDNA, proteins andantigens by Lactococcus lactis cell factories [J/OL]. Int. J. Mol. Sci., 2021, 22(3): 1379 [2023-02-22]. . |
63 | BAKARI S, LEMBROUK M, SOURD L, et al.. Lactococcus lactis is an efficient expression system for mammalian membrane proteins involved in liver detoxification, CYP3A4, and MGST1 [J]. Mol. Biotechnol., 2016, 58(4): 299-310. |
64 | MAO R, ZHOU K, HAN Z, et al.. Subtilisin QK-2: secretory expression in Lactococcus lactis and surface display onto gram-positive enhancer matrix (GEM) particles [J/OL]. Microb. Cell Fact., 2016, 15:80 [2023-02-22]. . |
65 | MA C, ZHANG L, GAO M, et al.. Construction of Lactococcus lactis expressing secreted and anchored Eimeria tenella 3-1E protein and comparison of protective immunity against homologous challenge [J]. Exp. Parasitol., 2017, 178:14-20. |
66 | RIBEIRO L A, AZEVEDO V, LE LOIR Y, et al.. Production and targeting of the Brucella abortus antigen L7/L12 in Lactococcus lactis: a first step towards food-grade live vaccines against brucellosis [J]. Appl. Environ. Microbiol., 2002, 68(2): 910-916. |
67 | PEREIRA V B, CUNHA V PDA, PREISSER T M, et al.. Lactococcus lactis carrying a DNA vaccine coding for the ESAT-6 antigen increases IL-17 cytokine secretion and boosts the BCG vaccine immune response [J]. J. Appl. Microbiol., 2017, 122(6): 1657-1662. |
68 | YAGNIK B, SHARMA D, PADH H, et al.. Immunization with r-Lactococcus lactis expressing outer membrane protein A of shigella dysenteriae type-1: evaluation of oral and intranasal route of administration [J]. J. Appl. Microbiol., 2017, 122(2): 493-505. |
69 | GOMES-SANTOS A C, DE OLIVEIRA R P, MOREIRA T G, et al.. Hsp65-producing Lactococcus lactis prevents inflammatory intestinal disease in mice by IL-10- and TLR2-dependent pathways [J/OL]. Front. Immunol., 2017, 8:30 [2023-02-22]. . |
70 | CARVALHO R D, BREYNER N, MENEZES-GARCIA Z, et al.. Secretion of biologically active pancreatitis-associated protein I (PAP) by genetically modified dairy Lactococcus lactis NZ9000 in the prevention of intestinal mucositis [J/OL]. Microb. Cell Fact., 2017, 16(1): 27 [2023-02-22]. . |
71 | KIM D, BECK B R, LEE S M, et al.. Pellet feed adsorbed with the recombinant Lactococcus lactis BFE920 expressing SiMA antigen induced strong recall vaccine effects against Streptococcus iniae infection in olive flounder (Paralichthys olivaceus) [J]. Fish Shellfish Immunol., 2016, 55:374-383. |
72 | LANG J, WANG X, LIU K, et al.. Oral delivery of staphylococcal nuclease by Lactococcus lactis prevents type 1 diabetes mellitus in NOD mice [J]. Appl. Microbiol. Biotechnol., 2017, 101(20): 7653-7262. |
73 | ZHOU B Y, SUN J C, LI X, et al.. Analysis of Immune responses in mice orally immunized with recombinant pMG36e-SP-TSOL18/Lactococcus lactis and pMG36e-TSOL18/Lactococcus lactis vaccines of Taenia solium [J/OL]. J. Immunol. Res., 2018, 2018: 9262631 [2023-02-22]. . |
74 | ZHANG R, WANG C, CHENG W, et al.. Delivery of Helicobacter pylori HpaA to gastrointestinal mucosal immune sites using Lactococcus lactis and its immune efficacy in mice [J]. Biotechnol. Lett., 2018, 40(3): 585-590. |
75 | LIU L, ZHANG W, SONG Y, et al.. Recombinant Lactococcus lactis co-expressing OmpH of an M cell-targeting ligand and IBDV-VP2 protein provide immunological protection in chickens [J]. Vaccine, 2018, 36(5): 729-735. |
76 | ZHOU J, WEI K, WANG C, et al.. Oral immunisation with Taishan Pinus massoniana pollen polysaccharide adjuvant with recombinant Lactococcus lactis-expressing Proteus mirabilis ompA confers optimal protection in mice [J]. Allergol. Immunopathol. (Madr), 2017, 45(5): 496-505. |
77 | TORKASHVAND A, BAHRAMI F, ADIB M, et al.. Mucosal and systemic immune responses elicited by recombinant Lactococcus lactis expressing a fusion protein composed of pertussis toxin and filamentous hemagglutinin from Bordetella pertussis [J]. Microb. Pathog., 2018, 120:155-160. |
78 | GUO M, YI S, GUO Y, et al.. Construction of a recombinant Lactococcus lactis strain expressing a variant porcine epidemic diarrhea virus S1 gene and its immunogenicity analysis in mice [J]. Viral Immunol., 2019, 32(3): 144-150. |
79 | SONG S, LI P, ZHANG R, et al.. Oral vaccine of recombinant Lactococcus lactis expressing the VP1 protein of duck hepatitis A virus type 3 induces mucosal and systemic immune responses [J]. Vaccine, 2019, 37(31): 4364-4369. |
80 | WANG C, ZHOU H, GUO F, et al.. Oral immunization of chickens with Lactococcus lactis expressing cjaA temporarily reduces campylobacter jejuni colonization [J]. Foodborne Pathog. Dis., 2020, 17(6): 366-372. |
81 | KUNJI E R, CHAN K W, SLOTBOOM D J, et al.. Eukaryotic membrane protein overproduction in Lactococcus lactis [J]. Curr. Opin. Biotechnol., 2005, 16(5): 546-551. |
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