综述与专题评论

乳铁蛋白的重组表达系统及法规管理现状概述

  • 吴晓文 ,
  • 张长太 ,
  • 李佳佳 ,
  • 凡孝菊 ,
  • 周景文
展开
  • 1(江苏创健医疗科技股份有限公司,江苏 常州,213000)
    2(江南大学 未来食品科学中心,江苏 无锡,214000)
第一作者: 硕士(凡孝菊高级工程师和周景文教授为共同通信作者,E-mail:fanxiaoju@trautec.com.cn;zhoujw1982@jiangnan.edu.cn)

收稿日期: 2023-04-20

  修回日期: 2023-06-05

  网络出版日期: 2024-06-11

基金资助

江苏省自然科学基金前沿引领技术基础研究专项(BK20202002)

Overview of recombinant expression systems and regulation status of lactoferrin

  • WU Xiaowen ,
  • ZHANG Changtai ,
  • LI Jiajia ,
  • FAN Xiaoju ,
  • ZHOU Jingwen
Expand
  • 1(Jiangsu Trautec Medical Technology Co.Ltd., Changzhou 213000, China)
    2(Science Center for Future Foods, Jiangnan University, Wuxi 214000, China)

Received date: 2023-04-20

  Revised date: 2023-06-05

  Online published: 2024-06-11

摘要

乳铁蛋白是一种铁结合糖蛋白,广泛存在于哺乳动物的乳汁和黏膜分泌物当中。乳铁蛋白具有广谱抑菌、抗病毒、免疫调节等生理功能,在婴幼儿配方乳粉、营养补充剂、化妆品等领域都有应用。近年来,随着基因工程技术的不断发展,来自不同物种的乳铁蛋白在常见的原核体系、真核体系与转基因哺乳动物中均得到了成功表达,重组产物的表达量及其与天然乳铁蛋白的结构相似度也在不断提升。该文对乳铁蛋白的生物学活性、重组表达系统以及目前的法规管理情况进行综述,并讨论了重组乳铁蛋白的研究难点和未来发展方向。

本文引用格式

吴晓文 , 张长太 , 李佳佳 , 凡孝菊 , 周景文 . 乳铁蛋白的重组表达系统及法规管理现状概述[J]. 食品与发酵工业, 2024 , 50(9) : 321 -329 . DOI: 10.13995/j.cnki.11-1802/ts.035889

Abstract

Lactoferrin is an iron-binding glycoprotein widely found in mammal milk and mucosal secretions.Lactoferrin has broad-spectrum antibacterial, antiviral, immunomodulatory, and other physiological functions, and is used in various fields, such as infant formula milk powder, nutritional supplements, and cosmetics.In recent years, with the continuous development of genetic engineering technology, lactoferrin from different species has been successfully expressed in common prokaryotic expression systems, eukaryotic expression systems, and transgenic mammals.Meanwhile, the expression of recombinant products and their structural similarity to natural lactoferrin have been increasing.This report reviewed the biological activity, recombinant expression systems, and current regulations of lactoferrin.Furthermore, the challenges and future development directions of recombinant lactoferrin were discussed.

参考文献

[1] SCHANBACHER F L, GOODMAN R E, TALHOUK R S.Bovine mammary lactoferrin:Implications from messenger ribonucleic acid (mRNA) sequence and regulation contrary to other milk Proteins[J].Journal of Dairy Science, 1993, 76(12):3812-3831.
[2] SORENSEN M, SORENSEN S P L. The proteins in whey[J]. Comptes rendus des Travaux du Laboratoire Carlsberg, 1939, 23(7): 55-99.
[3] JOHANSON B. Isolation of an iron-containing red protein from milk[J]. Acta Chemica Scandinavica, 1960, 14(2): 510-512.
[4] WANG B, TIMILSENA Y P, BLANCH E, et al.Lactoferrin:Structure, function, denaturation and digestion[J].Critical Reviews in Food Science and Nutrition, 2019, 59(4):580-596.
[5] METZ-BOUTIGUE M H, JOLLÈS J, MAZURIER J, et al.Human lactotransferrin:Amino acid sequence and structural comparisons with other transferrins[J].European Journal of Biochemistry, 1984, 145(3):659-676.
[6] BAKER H M, BAKER C J, SMITH C A, et al.Metal substitution in transferrins:Specific binding of cerium(IV) revealed by the crystal structure of cerium-substituted human lactoferrin[J].Journal of Biological Inorganic Chemistry:JBIC:a Publication of the Society of Biological Inorganic Chemistry, 2000, 5(6):692-698.
[7] TENG C T.Lactoferrin gene expression and regulation:An overview[J].Biochemistry and Cell Biology, 2002, 80(1):7-16.
[8] MOORE S A, ANDERSON B F, GROOM C R, et al.Three-dimensional structure of diferric bovine lactoferrin at 2.8 Å resolution[J].Journal of Molecular Biology, 1997, 274(2):222-236.
[9] WANG J R, TIAN Z G, TENG D, et al.Cloning, expression and characterization of Kunming mice lactoferrin and its N-lobe[J].Biometals:an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine, 2010, 23(3):523-530.
[10] DONG Z Y, ZHANG Y Z.Molecular cloning and expression of yak (Bos grunniens) lactoferrin cDNA in Pichia pastoris[J].Biotechnology Letters, 2006, 28(16):1285-1292.
[11] SUN X L, BAKER H M, SHEWRY S C, et al.Structure of recombinant human lactoferrin expressed in Aspergillus awamori[J].Acta Crystallographica.Section D, Biological Crystallography, 1999, 55(Pt 2):403-407.
[12] 许强, 王克夷.异源表达系统中蛋白质糖基化[J].生物化学与生物物理学报, 1999(2):111-115.
XU Q, WANG K Y.Protein glycosylation in heterologous expression system[J].Acta Biochimica et Biophysica Sinica, 1999(2):111-115.
[13] WANG X Y, GUO H Y, ZHANG W, et al.Effect of iron saturation level of lactoferrin on osteogenic activity in vitro and in vivo[J].Journal of Dairy Science, 2013, 96(1):33-39.
[14] LEGRAND D, ELASS E, CARPENTIER M, et al.Lactoferrin:A modulator of immune and inflammatory responses[J].Cellular and Molecular Life Sciences:CMLS, 2005, 62(22):2549-2559.
[15] HAYES T G, FALCHOOK G F, VARADHACHARY G R, et al.Phase I trial of oral talactoferrin Alfa in refractory solid tumors[J].Investigational New Drugs, 2006, 24(3):233-240.
[16] SINGH P K, PARSEK M R, GREENBERG E P, et al.A component of innate immunity prevents bacterial biofilm development[J].Nature, 2002, 417(6888):552-555.
[17] YAMAUCHI K, TOMITA M, GIEHL T J, et al.Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment[J].Infection and Immunity, 1993, 61(2):719-728.
[18] VALENTI P, ANTONINI G.Lactoferrin:An important host defence against microbial and viral attack[J].Cellular and Molecular Life Sciences:CMLS, 2005, 62(22):2576-2587.
[19] ELLISON R T, GIEHL T J.Killing of gram-negative bacteria by lactoferrin and lysozyme[J].Journal of Clinical Investigation, 1991, 88(4):1080-1091.
[20] ONISHI J, ROY M K, JUNEJA L R, et al.A lactoferrin-derived peptide with cationic residues concentrated in a region of its helical structure induces necrotic cell death in a leukemic cell line (HL-60)[J].Journal of Peptide Science:an Official Publication of the European Peptide Society, 2008, 14(9):1032-1038.
[21] FERNANDES K E, WEEKS K, CARTER D A.Lactoferrin is broadly active against yeasts and highly synergistic with amphotericin B[J].Antimicrobial Agents and Chemotherapy, 2020, 64(5):e02284-e02219.
[22] ANDRÉS M T, VIEJO-DÍAZ M, FIERRO J F.Human lactoferrin induces apoptosis-like cell death in Candida albicans:Critical role of K+-channel-mediated K+ efflux[J].Antimicrobial Agents and Chemotherapy, 2008, 52(11):4081-4088.
[23] ANDRÉS M T, ACOSTA-ZALDÍVAR M, GONZÁLEZ-SEISDEDOS J, et al.Cytosolic acidification is the first transduction signal of lactoferrin-induced regulated cell death pathway[J].International Journal of Molecular Sciences, 2019, 20(23):5838.
[24] ACOSTA-ZALDÍVAR M, ANDRÉS M T, REGO A, et al.Human lactoferrin triggers a mitochondrial- and caspase-dependent regulated cell death in Saccharomyces cerevisiae[J].Apoptosis:an International Journal on Programmed Cell Death, 2016, 21(2):163-173.
[25] HAMMER J, HAAHEIM H, GUTTEBERG T, et al.Bovine lactoferrin is more efficient than bovine lactoferricin in inhibiting HSV-I/-II replication in vitro[Z].Lactoferrin:structure, function and applications.Elsevier Science.2000:239-243
[26] MARCHETTI M, SUPERTI F, AMMENDOLIA M G, et al.Inhibition of poliovirus type 1 infection by iron-, manganese- and zinc-saturated lactoferrin[J].Medical Microbiology and Immunology, 1999, 187(4):199-204.
[27] HASEGAWA K, MOTSUCHI W, TANAKA S, et al.Inhibition with lactoferrin of in vitro infection with human herpes virus[J].Japanese Journal of Medical Science & Biology, 1994, 47(2):73-85.
[28] BELJAARS L, VAN DER STRATE B W A, BAKKER H I, et al.Inhibition of cytomegalovirus infection by lactoferrin in vitro and in vivo[J].Antiviral Research, 2004, 63(3):197-208.
[29] PUDDU P, BORGHI P, GESSANI S, et al.Antiviral effect of bovine lactoferrin saturated with metal ions on early steps of human immunodeficiency virus type 1 infection[J].The International Journal of Biochemistry & Cell Biology, 1998, 30(9):1055-1063.
[30] IKEDA M, NOZAKI A, SUGIYAMA K, et al.Characterization of antiviral activity of lactoferrin against hepatitis C virus infection in human cultured cells[J].Virus Research, 2000, 66(1):51-63.
[31] VAN DER STRATE B W A, BELJAARS L, MOLEMA G, et al.Antiviral activities of lactoferrin[J].Antiviral Research, 2001, 52(3):225-239.
[32] WEIMER K E D, ROARK H, FISHER K, et al.Breast milk and saliva lactoferrin levels and postnatal cytomegalovirus infection[J].American Journal of Perinatology, 2021, 38(10):1070-1077.
[33] SUPERTI F.Lactoferrin from bovine milk:A protective companion for life[J].Nutrients, 2020, 12(9):2562.
[34] 中国营养学会妇幼营养分会. 乳铁蛋白婴幼儿健康效应专家共识[J].临床儿科杂志, 2018, 36(11):884-888.
Maternal and Child Nutrition Branch of Chinese Nutrition Society.Expert consensus on the health effects of lactofemic in infants and young children[J].Journal of Clinical Pediatrics, 2018, 36(11):884-888.
[35] 中国医疗保健国际交流促进会营养与代谢管理分会. 乳铁蛋白临床应用中国专家共识[J].中华预防医学杂志, 2022, 56(12):1694-1701.
Nutrition and Metabolism Management Branch of China International Exchange and Promotive Association for Medical and Health Care.Consensus of Chinese experts on clinical application of lactoferrin[J].Chinese Journal of Preventive Medicine, 2022, 56(12):1694-1701.
[36] GONZÁLEZ-CHÁVEZ S A, ARÉVALO-GALLEGOS S, RASCÓN-CRUZ Q.Lactoferrin:Structure, function and applications[J].International Journal of Antimicrobial Agents, 2009, 33(4):301.e1-301.e8.
[37] 刘中原, 李延平.细菌脂多糖的生物活性及作用机制[J].医学综述, 2010, 16(2):166-169.
LIU Z Y, LI Y P.Biological activity and mechanism of bacterial lipopolysaccharide[J].Medical Recapitulate, 2010, 16(2):166-169.
[38] HU L L, GAO C H, HONG C, et al.Expression, purification, and breast cancer cell inhibiting effect of recombinant human lactoferrin C-lobe[J].Bioscience, Biotechnology, and Biochemistry, 2016, 80(2):257-263.
[39] GARCÍA-MONTOYA I, GONZÁLEZ-CHÁVEZ S A, SALAZAR-MARTÍNEZ J, et al.Expression and characterization of recombinant bovine lactoferrin in E.coli[J].Biometals:an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine, 2013, 26(1):113-122.
[40] JIN L, LI L H, ZHOU L X, et al.Improving expression of bovine lactoferrin N-lobe by promoter optimization and codon engineering in Bacillus subtilis and its antibacterial activity[J].Journal of Agricultural and Food Chemistry, 2019, 67(35):9749-9756.
[41] WEINBERG E D.The Lactobacillus anomaly:Total iron abstinence[J].Perspectives in Biology and Medicine, 1997, 40(4):578-583.
[42] GRZYWACZ K, BUTCHER J, ROMAIN G, et al.The impact of probiotics and lactoferrin supplementation on piglet gastrointestinal microbial communities[J].Biometals:an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine, 2019, 32(3):533-543.
[43] CHEN H L, LAI Y W, CHEN C S, et al.Probiotic Lactobacillus casei expressing human lactoferrin elevates antibacterial activity in the gastrointestinal tract[J].Biometals:an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine, 2010, 23(3):543-554.
[44] JENKINS N, PAREKH R B, JAMES D C.Getting the glycosylation right:Implications for the biotechnology industry[J].Nature Biotechnology, 1996, 14(8):975-981.
[45] LIANG Q W, RICHARDSON T.Expression and characterization of human lactoferrin in yeast Saccharomyces cerevisiae[J].Journal of Agricultural and Food Chemistry, 1993, 41(10):1800-1807.
[46] 唐香山, 张学文.酿酒酵母表达系统[J].生命科学研究, 2004, 8(S1):106-109.
TANG X S, ZHANG X W.Saccharomyces serevisiae expression system[J].Life Science Research, 2004, 8(S1):106-109.
[47] PARAMASIVAM M, SARAVANAN K, UMA K, et al.Expression, purification, and characterization of equine lactoferrin in Pichia pastoris[J].Protein Expression and Purification, 2002, 26(1):28-34.
[48] IGLESIAS-FIGUEROA B, VALDIVIEZO-GODINA N, SIQUEIROS-CENDÓN T, et al.High-level expression of recombinant bovine lactoferrin in Pichia pastoris with antimicrobial activity[J].International Journal of Molecular Sciences, 2016, 17(6):902.
[49] LI J B, ZHU W Z, LUO M R, et al.Molecular cloning, expression and purification of lactoferrin from Tibetan sheep mammary gland using a yeast expression system[J].Protein Expression and Purification, 2015, 109:35-39.
[50] ZHANG T, LIU H, LV B, et al.Regulating strategies for producing carbohydrate active enzymes by filamentous fungal cell factories[J].Frontiers in Bioengineering and Biotechnology, 2020, 8:691.
[51] WARD P P, MAY G S, HEADON D R, et al.An inducible expression system for the production of human lactoferrin in Aspergillus nidulans[J].Gene, 1992, 122(1):219-223.
[52] WARD P P, LO J Y, DUKE M, et al.Production of biologically active recombinant human lactoferrin in Aspergillus oryzae[J].Bio/technology (Nature Publishing Company), 1992, 10(7):784-789.
[53] WARD P P, PIDDINGTON C S, CUNNINGHAM G A, et al.A system for production of commercial quantities of human lactoferrin:A broad spectrum natural antibiotic[J].Bio/technology (Nature Publishing Company), 1995, 13(5):498-503.
[54] RAMALINGAM S S, CRAWFORD J, CHANG A, et al.Fortis-M, a randomized, double-blind, placebo-controlled phase 3 study of oral talactoferrin Alfa with best supportive care in patients with advanced non-small cell lung cancer following two or more prior regimens- by the fortis-M study group[J].Annals of Oncology, 2012, 23:ixe23.
[55] WEBER W, FUSSENEGGER M.Inducible gene expression in mammalian cells and mice[J].Methods in Molecular Biology, 2004, 267:451-466.
[56] WANG M, SUN Z L, YU T, et al.Large-scale production of recombinant human lactoferrin from high-expression, marker-free transgenic cloned cows[J].Scientific Reports, 2017, 7(1):10733.
[57] CUI S X, LV X Q, SUN G Y, et al.Recent advances and prospects in purification and heterologous expression of lactoferrin[J].Food Bioengineering, 2022, 1(1):58-67.
[58] YU H Q, CHEN J Q, SUN W, et al.The dominant expression of functional human lactoferrin in transgenic cloned goats using a hybrid lactoferrin expression construct[J].Journal of Biotechnology, 2012, 161(3):198-205.
[59] CUI D, LI J, ZHANG L L, et al.Generation of bi-transgenic pigs overexpressing human lactoferrin and lysozyme in milk[J].Transgenic Research, 2015, 24(2):365-373.
[60] NUIJENS J H, VAN BERKEL P H C, GEERTS M E J, et al.Characterization of recombinant human lactoferrin secreted in milk of transgenic mice[J].Journal of Biological Chemistry, 1997, 272(13):8802-8807.
[61] VAN BERKEL P H C, WELLING M M, GEERTS M, et al.Large scale production of recombinant human lactoferrin in the milk of transgenic cows[J].Nature Biotechnology, 2002, 20(5):484-487.
[62] STOWELL K M, RADO T A, FUNK W D, et al.Expression of cloned human lactoferrin in baby-hamster kidney cells[J].The Biochemical Journal, 1991, 276 (Pt 2):349-355.
[63] KRUZEL M L, ACTOR J K, ZIMECKI M, et al.Novel recombinant human lactoferrin:Differential activation of oxidative stress related gene expression[J].Journal of Biotechnology, 2013, 168(4):666-675.
[64] SEMAK I, BUDZEVICH A, MALIUSHKOVA E, et al.Development of dairy herd of transgenic goats as biofactory for large-scale production of biologically active recombinant human lactoferrin[J].Transgenic Research, 2019, 28(5-6):465-478.
[65] 纪颖, 艾连中, 邢明霞, 等.基于牛乳铁蛋白的生产技术创新及应用研究进展[J].食品与发酵工业, 2022, 48(15):332-340.
JI Y, AI L Z, XING M X, et al.Advances on bovine lactoferrin-based technical innovation and application[J].Food and Fermentation Industries, 2022, 48(15):332-340.
[66] KROLITZKI E, SCHWAMINGER S P, PAGEL M, et al.Current practices with commercial scale bovine lactoferrin production and alternative approaches[J].International Dairy Journal, 2022, 126:105263.
[67] WAKABAYASHI H, YAMAUCHI K, ABE F.Quality control of commercial bovine lactoferrin[J].Biometals:an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine, 2018, 31(3):313-319.
[68] CONESA C, CALVO M, SÁNCHEZ L.Recombinant human lactoferrin:A valuable protein for pharmaceutical products and functional foods[J].Biotechnology Advances, 2010, 28(6):831-838.
[69] ZHOU C, SUN N.Allergenicity assessment of a genetically modified protein-recombinant human lactoferrin[J].Journal of Allergy & Therapy, 2013, S3:1-6.
[70] 戴亚妮, 杨雪珍, 刘燊, 等.重组人乳铁蛋白急性经口毒性试验和90天喂养试验[J].卫生研究, 2018, 47(2):286-289;311.
DAI Y N, YANG X Z, LIU S, et al.Acute oral toxicity and 90 days feeding test of recombinant human lactoferrin[J].Journal of Hygiene Research, 2018, 47(2):286-289;311.
[71] TurtleTree steps into functional protein space with world’s first fermentation-produced lactoferrin.[EB/OL].Food Ingredients First 819, 2022 https://wwwfoodingredientsfirstcom/news/turtletree-steps-into-functional-protein-space-with-worlds-first-fermentation-produced-lactoferrinhtml.
[72] De novo dairy milks new cult food science investment into scaling precision fermentation dairy[EB/OL].Food Ingredients First 282, 2022 https://wwwfoodingredientsfirstcom/news/de-novo-dairy-milks-new-cult-food-science-investment-into-scaling-precision-fermentation-dairyhtml.
文章导航

/