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A Review on the Use of the Signal Peptide in Recombinant Interferon beta Secretion in Escherichia coli

Yıl 2019, Cilt 45, Sayı 1, 10 - 21, 30.04.2019

Öz

Eukaryotic and prokaryotic expression systems are used with similar processes for the production of rIFN-β1a and rIFN-β1b which are from the recombinant interferon beta (rIFN-β) protein varieties. The difficulties in purification of the produced rIFN-β1a by eukaryotic expression systems and the influence of its biological activity make recombinant protein production difficult with these processes. In the production of rIFN-β1b, where prokaryotic expression systems were used, purification and activity problems were found to be less frequent. Better use of product secretion capability in Escherichia coli from prokaryotic bacteria indicates that this system will be preferred in the production of rIfN-β1b. If the construct is designed to secrete recombinant proteins out of the host cell from which the recombinant proteins are produced, it is envisaged that the host cells will not fragment during purification, thereby facilitating product purification processes. The use of E. coli with type I and type II secretion in the production of rIFN-β1b proteins will reduce the purification and activity problems in the secretion of rIFN-β1b produced in this host, as well as the toxic effect of rIFN-β1b to the host cell is expected to diminish. To this end, various approaches are contemplated to overcome the disadvantages of the E. coli production system, such as transferring the DmsA signal peptide, the Tat-type signal peptide, to the expression vector pET22b, in addition to the PelB signal peptide, the Sec signal peptide. In this review, information about the properties of IFNs, the clinical applications of rIFN-β and the researches based on the investigations of rIFN-β1b production  methods, and information about the use of signal peptides in the process of producing rIFN-β1b in E. coli host cells were highlighted.

Kaynakça

  • Allen J, Feng P, Patkar A, Haney KL, Chew L Sengchanthalangsy LLP (2015). Method for producing soluble recombinant interferon protein without denaturing. US20160032345A1.
  • Beladiya C, Tripathy RK, Bajaj P, Aggarwal G, Pande AH (2015). Expression, purification and immobilization of recombinant AiiA enzyme onto magnetic nanoparticles. Protein Expression and Purification 113: 56-62. DOI: 10.1016/j.pep.2015.04.014
  • Binet R, Létoffé S, Ghigo JM, Delepelaire P, Wandersman C (1997). Protein secretion by gram-negative bacterial ABC exporters–a review. Gene 192: 7-11. PMID: 9224868
  • Chelbi-Alix, M.K., Wietzerbin, J. (2007). “IFN, a growing cytokine family: 50 years of IFN research”, Biochimie, 89, 713-718. DOI: 10.1016/j.biochi.2007.05.001
  • Chevaliez S, Pawlotsky JM (2009). Interferons and Their Use in Persistent Viral Infections. In: Kräusslich HG, Bartenschlager R. (eds) Antiviral strategies. Handbook of Experimental Pharmacol 189 Springer Berlin Heidelberg. e-ISBN 978-3-540-79086-0
  • Choi JH, Lee SY (2004). Secretory and extracellular production of recombinant proteins using Escherichia coli. Appl Microbiol and Biotech 64: 625-635. DOI: 10.1007/s00253-004-1559-9
  • Cianciotto NP (2005). Type II secretion: a protein secretion system for all seasons. Trends in Microbiol 13(12): 581-588. DOI: 10.1016/j.tim.2005.09.005
  • Conradt HS, Egge H, Peter-Katalinic J, Reiser W, Siklosi T, Schaper K (1987). Structure of the carbohydrate moiety of human IFN-ß secreted by a recombinant Chinese hamster ovary cell line. J of Biological Chem 262: 14600-14605.
  • Dissing-Olesen L, Thaysen-Andersen M, Meldgaard M, Højrup P, Finsen B (2008). The function of the human IFN-ß 1a glycan determined in vivo. J of Pharmacol and Experimental Therapeutics 326: 338-347. DOI: 10.1124/jpet.108.138263
  • Feizi A, Österlund T, Petranovic D, Bordel S, Nielsen J (2013). Genome-scale modeling of the protein secretory machinery in yeast. PLoS One 8: 1-13. DOI: 10.1371/journal.pone.0063284
  • Goodbourn S, Didcock L, Randall RE (2000). Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. J of General Virol 81: 2341–2364. DOI: 10.1099/0022-1317-81-10-2341
  • Hermant P, Michaels T (2014). Interferon-λ in the context of viral infections: production, response and therapeutic implications. J of Innate Immunity 6: 563-574. DOI: 10.1159/000360084
  • Kamionka, M (2011). Engineering of therapeutic proteins production in Escherichia coli. Current Pharmaceut Biotech 12: 268-274. DOI : 0.2174/138920111794295693
  • Kagawa Y, Takasaki S, Utsumi J, Hosoi K, Shimizu H, Kochibe N, Kobata A (1988). Comparative study of the asparagine-linked sugar chains of natural human IFN-β 1 and recombinant human IFN-β 1 produced by three different mammalian cells. J of Biological Chem 263: 17508-17515.
  • Kieseier BC, Arnold DL, Balcer LJ, Boyko AA, Pelletier J, Liu S, Zhu Y, Seddighzadeh A, Hung S, Deykin A, Sheikh SI, Calabresi PA (2015). Peginterferon beta-1a in multiple sclerosis: 2-year results from ADVANCE. Multiple Sclerosis J 21: 1025-1035. DOI: 10.1177/1352458514557986
  • Mark DF, Lu SD, Creasey AA, Yamamoto R, Lin LS (1984). Site-specific mutagenesis of the human fibroblast IFN gene. Proc Nat Acad Sci USA. 81: 5662-5666. DOI: 10.1073/pnas.81.18.5662
  • Mattanovich D, Gasser B, Hohenblum H, Sauer M (2004). Stress in recombinant protein producing yeasts. J of Biotech 113: 112-135. DOI: 10.1016/j.jbiotec.2004.04.035
  • Mergulhao FJ, Summers DK, Monteiro GA (2005). Recombinant protein secretion in Escherichia coli. Biotech Adv 23: 177-202. DOI: 10.1016/j.biotechadv.2004.11.003
  • Moradian C, Fazeli MR, Abedi D (2013). Over expression of the Interferon ß-1b by optimizing induction conditions using response surface methodology. J of Biology and Today's World 2: 217-226. DOI: 10.15412/J.JBTW.01020401
  • Morowvat MH, Babaeipour V, Rajabi-Memari H, Vahidi H, Maghsoudi N (2014). Overexpression of recombinant human beta interferon (rhINF-ß) in periplasmic space of Escherichia coli. Iranian J of Pharmaceut Res 13: 151-60.
  • Morowvat, M.H., Babaeipour, V., Memari, H.R., Vahidi, H. (2015). “Optimization of fermentation conditions for recombinant human interferon beta production by Escherichia coli using the response surface methodology”, Jundishapur J of Microbiol 8: 1-9 101. DOI: 10.5812/jjm.8(4)2015.16236
  • Parker BS, Rautela J, Hertzog PJ (2016). Antitumour actions of interferons: implications for cancer therapy. Nature Rev Cancer 16: 131-144. DOI: 10.1038/nrc.2016.14
  • Pestka S, Langer JA, Zoon KC, Samuel CE (1987). Interferons and their actions. Ann Rev of Biochem 56(1): 727-777. DOI: 10.1146/annurev.bi.56.070187.003455 Pestka S, Krause CD, Walter MR (2004). Interferons, interferon-like cytokines, and their receptors. Immunol Rev 202: 8-32. DOI: 10.1111/j.0105-2896.2004.00204.x
  • Rao DVK, Ramu CT, Rao JV, Narasu ML, Rao AKSB (2009). Cloning, High Expression and Purification of Recombinant Human Interferon-ß-1b in Escherichia coli. Appl Biochem Biotech 158: 140–154. DOI: 10.1007/s12010-008-8318-9
  • Randall RE, Goodbourn S (2008). Interferons and viruses: An interplay between induction, signalling, antiviral responses and virus countermeasures. J General Virology 89: 1–47. DOI: 10.1099/vir.0.83391-0
  • Rodriguez J, Spearman M, Tharmalingam T, Sunley K, Lodewyks C, Huzel N, Butler M (2010). High productivity of human recombinant beta-interferon from a low-temperature perfusion culture. J. Biotech 150: 509-518. DOI: 10.1016/j.jbiotec.2010.09.959
  • Sambrook J, Russel DW (2001). Molecular Cloning: A Laboratory Manual 3rd ed Cold Spring Harbor Laboratory Press, New York, USA.
  • Sasaki R, Kanda T, Nakamoto S, Haga Y, Nakamura M, Yasui S, Jiang X, Wu S, Arai M, Yokosuka O (2015). Natural interferon-beta treatment for patients with chronic hepatitis C in Japan. World J. Hepatol 7: 1125-1132. DOI: 10.4254/wjh.v7.i8.1125
  • Schmidt FR (2004). Recombinant expression systems in the pharmaceutical industry. Appl Microbiol Biotech 65: 363-372. DOI: 10.1007/s00253-004-1656-9
  • Sivashanmugam A, Murray V, Cui C, Zhang Y, Wang J, Li Q (2009). Practical protocols for production of very high yields of recombinant proteins using Escherichia coli. Protein Sci 18: 936-948. DOI: 10.1002/pro.102
  • Smeekens SP, Ng A, Kumar V, Johnson MD, Plantinga TS, van Diemen C, Arts P, Verwiel ET, Gresnigt MS, Fransen K, van Sommeren S, Oosting M, Cheng SC, Joosten LA, Hoischen A, Kullberg BJ, Scott WK, Perfect JR, van der Meer JW, Wijmenga C, Netea MG, Xavier RJ (2013). Functional genomics identifies type I IFN pathway as central for host defense against Candida albicans. Nature Commun 4: 1342. DOI: 10.1038/ncomms2343
  • Sorensen PS, Ross C, Clemmesen KM, Bendtzen K, Frederiksen JL, Jensen K, Kristensen O, Petersen T, Rasmussen S, Ravnborg M, Stenager E, Koch-Henriksen N (2003). Danish Multiple Sclerosis Study Group. Clinical importance of neutralising antibodies against IFN β in patients with relapsing-remitting multiple sclerosis. Lancet 362: 1184-91. DOI: 10.1016/S0140-6736(03)14541-2
  • Stefan A, Alfarano P, Merulla D, Mattana P, Rolli E, Mangino P, Masotti L, Hochkoeppler A (2009). The regulatory elements of araBAD operon, contrary to lac-based expression systems, afford hypersynthesis of murine and human IFNs in Escherichia coli. Biotech Prog 25: 1612-1619. DOI: 10.1002/btpr.270
  • Stifter SA, Gould JA, Mangan NE, Reid HH, Rossjohn J, Hertzog PJ, de Weerd NA (2014). Purification and biological characterization of soluble, recombinant mouse IFN-ß expressed in insect cells. Protein Exp Purif 94: 7–14. DOI: 10.1016/j.pep.2013.10.019
  • Tayal V, Kalra BS (2008). Cytokines and anti-cytokines as therapeutics-an update. Eur J Pharmacol 579: 1-12. DOI: 10.1016/j.ejphar.2007.10.049
  • vanBeers MMC, Sauerborn M, Gilli F, Brinks V, Schellekens H, Jiskoot W (2011). Oxidized and aggregated recombinant human interferon beta is immunogenic in human interferon beta transgenic mice. Pharmaceut Res 28: 2393–2402. DOI: 10.1007/s11095-011-0451-4.
  • Villela AD, Renard G, Palma MS, Chies JM, Dalmora SL, Basso LA, Santos, DS (2010). Human IFN β1ser17: coding DNA synthesis, expression, purification and characterization of bioactive recombinant protein. J of Microbial & Biochemical Tech 2: 111-117.
  • Walsh G (2014). Biopharmaceut Benchmarks. Nature Biotech 32: 992–1000.

Escherichia coli’de Yenibileşenli İnterferon beta Salgılanmasında Sinyal Peptidi Kullanımı Üzerine bir Derleme

Yıl 2019, Cilt 45, Sayı 1, 10 - 21, 30.04.2019

Öz

: Rekombinant interferon beta (rİFN-β) proteini çeşitlerinden rİFN-β1a ve rİFN-β1b üretimi için benzer süreçler ile ökaryotik ve prokaryotik ekspresyon sistemleri kullanılmaktadır. Ökaryotik ekspresyon sistemleri ile üretilen rİFN-β1a’nın saflaştırılmasında zorlukların yaşanması ve biyolojik aktivitesinin etkilenmesi bu süreçler ile rekombinant protein üretimini güçleştirmektedir. Prokaryotik ekspresyon sistemlerinin kullanıldığı rİFN-β1b üretiminde ise saflaştırma ve aktivite sorunlarının daha az gerçekleştiği belirlenmiştir. Prokaryotik bakterilerden Escherichia coli’de bulunan ürün salgılama özelliğinin daha iyi kullanılması, bu sistemin rİFN-β1b üretiminde daha fazla tercih edileceğini göstermektedir. Rekombinant proteinlerin üretildikleri konakçı hücreden dışarı salgılatılacak şekilde yapı tasarlanması durumunda, saflaştırma sırasında E. coli konakçı hücreler parçalanmayacağından ürün saflaştırma işlemlerini kolaylaştıracağı öngörülmektedir. Tip I ve tip II salgılama sistemine sahip olan E. coli’nin rİFN-β1b proteinlerinin üretiminde kullanımı, bu konakçıda üretilen rİFN-β1b’nin hücre dışına salgılatılmasında saflaştırma ve aktivite sorunlarını azaltacağı, ayrıca rİFN-β1b’nin konakçı hücreye yapacağı toksik etkininde ortadan kalkacağı tahmin edilmektedir. Bu amaçla E. coli üretim sistemindeki dezavantajları gidermek için Sec sinyal peptidi olan PelB sinyal peptidine ilave olarak Tat tipi sinyal peptidi olan DmsA sinyal peptidi’nin pET22b ifade vektörüne aktarılmasıyla rİFN-β1b proteinlerinin hücre dışına salgılatılması işlemi gibi çeşitli yaklaşımlar tasarlanmaktadır. Bu derlemede, İFN’ların özelliklerine, rİFN-β’nın klinik uygulamalarına ve rİFN-β1b üretim yöntemleri ile ilgili yapılmış araştırmalara dayalı bilgi ve ve rİFN-β1b’nin E. coli konakçı hücrelerinde üretilmesi sürecinde sinyal peptidlerinin kullanımı ile ilgili bilgilere dikkat çekilmiştir.

Kaynakça

  • Allen J, Feng P, Patkar A, Haney KL, Chew L Sengchanthalangsy LLP (2015). Method for producing soluble recombinant interferon protein without denaturing. US20160032345A1.
  • Beladiya C, Tripathy RK, Bajaj P, Aggarwal G, Pande AH (2015). Expression, purification and immobilization of recombinant AiiA enzyme onto magnetic nanoparticles. Protein Expression and Purification 113: 56-62. DOI: 10.1016/j.pep.2015.04.014
  • Binet R, Létoffé S, Ghigo JM, Delepelaire P, Wandersman C (1997). Protein secretion by gram-negative bacterial ABC exporters–a review. Gene 192: 7-11. PMID: 9224868
  • Chelbi-Alix, M.K., Wietzerbin, J. (2007). “IFN, a growing cytokine family: 50 years of IFN research”, Biochimie, 89, 713-718. DOI: 10.1016/j.biochi.2007.05.001
  • Chevaliez S, Pawlotsky JM (2009). Interferons and Their Use in Persistent Viral Infections. In: Kräusslich HG, Bartenschlager R. (eds) Antiviral strategies. Handbook of Experimental Pharmacol 189 Springer Berlin Heidelberg. e-ISBN 978-3-540-79086-0
  • Choi JH, Lee SY (2004). Secretory and extracellular production of recombinant proteins using Escherichia coli. Appl Microbiol and Biotech 64: 625-635. DOI: 10.1007/s00253-004-1559-9
  • Cianciotto NP (2005). Type II secretion: a protein secretion system for all seasons. Trends in Microbiol 13(12): 581-588. DOI: 10.1016/j.tim.2005.09.005
  • Conradt HS, Egge H, Peter-Katalinic J, Reiser W, Siklosi T, Schaper K (1987). Structure of the carbohydrate moiety of human IFN-ß secreted by a recombinant Chinese hamster ovary cell line. J of Biological Chem 262: 14600-14605.
  • Dissing-Olesen L, Thaysen-Andersen M, Meldgaard M, Højrup P, Finsen B (2008). The function of the human IFN-ß 1a glycan determined in vivo. J of Pharmacol and Experimental Therapeutics 326: 338-347. DOI: 10.1124/jpet.108.138263
  • Feizi A, Österlund T, Petranovic D, Bordel S, Nielsen J (2013). Genome-scale modeling of the protein secretory machinery in yeast. PLoS One 8: 1-13. DOI: 10.1371/journal.pone.0063284
  • Goodbourn S, Didcock L, Randall RE (2000). Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. J of General Virol 81: 2341–2364. DOI: 10.1099/0022-1317-81-10-2341
  • Hermant P, Michaels T (2014). Interferon-λ in the context of viral infections: production, response and therapeutic implications. J of Innate Immunity 6: 563-574. DOI: 10.1159/000360084
  • Kamionka, M (2011). Engineering of therapeutic proteins production in Escherichia coli. Current Pharmaceut Biotech 12: 268-274. DOI : 0.2174/138920111794295693
  • Kagawa Y, Takasaki S, Utsumi J, Hosoi K, Shimizu H, Kochibe N, Kobata A (1988). Comparative study of the asparagine-linked sugar chains of natural human IFN-β 1 and recombinant human IFN-β 1 produced by three different mammalian cells. J of Biological Chem 263: 17508-17515.
  • Kieseier BC, Arnold DL, Balcer LJ, Boyko AA, Pelletier J, Liu S, Zhu Y, Seddighzadeh A, Hung S, Deykin A, Sheikh SI, Calabresi PA (2015). Peginterferon beta-1a in multiple sclerosis: 2-year results from ADVANCE. Multiple Sclerosis J 21: 1025-1035. DOI: 10.1177/1352458514557986
  • Mark DF, Lu SD, Creasey AA, Yamamoto R, Lin LS (1984). Site-specific mutagenesis of the human fibroblast IFN gene. Proc Nat Acad Sci USA. 81: 5662-5666. DOI: 10.1073/pnas.81.18.5662
  • Mattanovich D, Gasser B, Hohenblum H, Sauer M (2004). Stress in recombinant protein producing yeasts. J of Biotech 113: 112-135. DOI: 10.1016/j.jbiotec.2004.04.035
  • Mergulhao FJ, Summers DK, Monteiro GA (2005). Recombinant protein secretion in Escherichia coli. Biotech Adv 23: 177-202. DOI: 10.1016/j.biotechadv.2004.11.003
  • Moradian C, Fazeli MR, Abedi D (2013). Over expression of the Interferon ß-1b by optimizing induction conditions using response surface methodology. J of Biology and Today's World 2: 217-226. DOI: 10.15412/J.JBTW.01020401
  • Morowvat MH, Babaeipour V, Rajabi-Memari H, Vahidi H, Maghsoudi N (2014). Overexpression of recombinant human beta interferon (rhINF-ß) in periplasmic space of Escherichia coli. Iranian J of Pharmaceut Res 13: 151-60.
  • Morowvat, M.H., Babaeipour, V., Memari, H.R., Vahidi, H. (2015). “Optimization of fermentation conditions for recombinant human interferon beta production by Escherichia coli using the response surface methodology”, Jundishapur J of Microbiol 8: 1-9 101. DOI: 10.5812/jjm.8(4)2015.16236
  • Parker BS, Rautela J, Hertzog PJ (2016). Antitumour actions of interferons: implications for cancer therapy. Nature Rev Cancer 16: 131-144. DOI: 10.1038/nrc.2016.14
  • Pestka S, Langer JA, Zoon KC, Samuel CE (1987). Interferons and their actions. Ann Rev of Biochem 56(1): 727-777. DOI: 10.1146/annurev.bi.56.070187.003455 Pestka S, Krause CD, Walter MR (2004). Interferons, interferon-like cytokines, and their receptors. Immunol Rev 202: 8-32. DOI: 10.1111/j.0105-2896.2004.00204.x
  • Rao DVK, Ramu CT, Rao JV, Narasu ML, Rao AKSB (2009). Cloning, High Expression and Purification of Recombinant Human Interferon-ß-1b in Escherichia coli. Appl Biochem Biotech 158: 140–154. DOI: 10.1007/s12010-008-8318-9
  • Randall RE, Goodbourn S (2008). Interferons and viruses: An interplay between induction, signalling, antiviral responses and virus countermeasures. J General Virology 89: 1–47. DOI: 10.1099/vir.0.83391-0
  • Rodriguez J, Spearman M, Tharmalingam T, Sunley K, Lodewyks C, Huzel N, Butler M (2010). High productivity of human recombinant beta-interferon from a low-temperature perfusion culture. J. Biotech 150: 509-518. DOI: 10.1016/j.jbiotec.2010.09.959
  • Sambrook J, Russel DW (2001). Molecular Cloning: A Laboratory Manual 3rd ed Cold Spring Harbor Laboratory Press, New York, USA.
  • Sasaki R, Kanda T, Nakamoto S, Haga Y, Nakamura M, Yasui S, Jiang X, Wu S, Arai M, Yokosuka O (2015). Natural interferon-beta treatment for patients with chronic hepatitis C in Japan. World J. Hepatol 7: 1125-1132. DOI: 10.4254/wjh.v7.i8.1125
  • Schmidt FR (2004). Recombinant expression systems in the pharmaceutical industry. Appl Microbiol Biotech 65: 363-372. DOI: 10.1007/s00253-004-1656-9
  • Sivashanmugam A, Murray V, Cui C, Zhang Y, Wang J, Li Q (2009). Practical protocols for production of very high yields of recombinant proteins using Escherichia coli. Protein Sci 18: 936-948. DOI: 10.1002/pro.102
  • Smeekens SP, Ng A, Kumar V, Johnson MD, Plantinga TS, van Diemen C, Arts P, Verwiel ET, Gresnigt MS, Fransen K, van Sommeren S, Oosting M, Cheng SC, Joosten LA, Hoischen A, Kullberg BJ, Scott WK, Perfect JR, van der Meer JW, Wijmenga C, Netea MG, Xavier RJ (2013). Functional genomics identifies type I IFN pathway as central for host defense against Candida albicans. Nature Commun 4: 1342. DOI: 10.1038/ncomms2343
  • Sorensen PS, Ross C, Clemmesen KM, Bendtzen K, Frederiksen JL, Jensen K, Kristensen O, Petersen T, Rasmussen S, Ravnborg M, Stenager E, Koch-Henriksen N (2003). Danish Multiple Sclerosis Study Group. Clinical importance of neutralising antibodies against IFN β in patients with relapsing-remitting multiple sclerosis. Lancet 362: 1184-91. DOI: 10.1016/S0140-6736(03)14541-2
  • Stefan A, Alfarano P, Merulla D, Mattana P, Rolli E, Mangino P, Masotti L, Hochkoeppler A (2009). The regulatory elements of araBAD operon, contrary to lac-based expression systems, afford hypersynthesis of murine and human IFNs in Escherichia coli. Biotech Prog 25: 1612-1619. DOI: 10.1002/btpr.270
  • Stifter SA, Gould JA, Mangan NE, Reid HH, Rossjohn J, Hertzog PJ, de Weerd NA (2014). Purification and biological characterization of soluble, recombinant mouse IFN-ß expressed in insect cells. Protein Exp Purif 94: 7–14. DOI: 10.1016/j.pep.2013.10.019
  • Tayal V, Kalra BS (2008). Cytokines and anti-cytokines as therapeutics-an update. Eur J Pharmacol 579: 1-12. DOI: 10.1016/j.ejphar.2007.10.049
  • vanBeers MMC, Sauerborn M, Gilli F, Brinks V, Schellekens H, Jiskoot W (2011). Oxidized and aggregated recombinant human interferon beta is immunogenic in human interferon beta transgenic mice. Pharmaceut Res 28: 2393–2402. DOI: 10.1007/s11095-011-0451-4.
  • Villela AD, Renard G, Palma MS, Chies JM, Dalmora SL, Basso LA, Santos, DS (2010). Human IFN β1ser17: coding DNA synthesis, expression, purification and characterization of bioactive recombinant protein. J of Microbial & Biochemical Tech 2: 111-117.
  • Walsh G (2014). Biopharmaceut Benchmarks. Nature Biotech 32: 992–1000.

Ayrıntılar

Birincil Dil Türkçe
Konular Biyoloji
Bölüm Araştırma Makaleleri
Yazarlar

Mehmet ÖZTÜRK (Sorumlu Yazar)
BOLU ABANT İZZET BAYSAL ÜNİVERSİTESİ
Türkiye


Yakup ERMURAT
BOLU ABANT İZZET BAYSAL ÜNİVERSİTESİ
Türkiye

Yayımlanma Tarihi 30 Nisan 2019
Yayınlandığı Sayı Yıl 2019, Cilt 45, Sayı 1

Kaynak Göster

Bibtex @derleme { sufefd454514, journal = {Selçuk Üniversitesi Fen Fakültesi Fen Dergisi}, issn = {}, eissn = {2458-9411}, address = {Selçuk Üniversitesi Fen Fakültesi Biyoloji Bölümü 3. Kat No: 324, Selçuklu, 42250, KONYA}, publisher = {Selçuk Üniversitesi}, year = {2019}, volume = {45}, pages = {10 - 21}, doi = {}, title = {Escherichia coli’de Yenibileşenli İnterferon beta Salgılanmasında Sinyal Peptidi Kullanımı Üzerine bir Derleme}, key = {cite}, author = {Öztürk, Mehmet and Ermurat, Yakup} }
APA Öztürk, M. & Ermurat, Y. (2019). Escherichia coli’de Yenibileşenli İnterferon beta Salgılanmasında Sinyal Peptidi Kullanımı Üzerine bir Derleme . Selçuk Üniversitesi Fen Fakültesi Fen Dergisi , 45 (1) , 10-21 . Retrieved from https://dergipark.org.tr/tr/pub/sufefd/issue/44924/454514
MLA Öztürk, M. , Ermurat, Y. "Escherichia coli’de Yenibileşenli İnterferon beta Salgılanmasında Sinyal Peptidi Kullanımı Üzerine bir Derleme" . Selçuk Üniversitesi Fen Fakültesi Fen Dergisi 45 (2019 ): 10-21 <https://dergipark.org.tr/tr/pub/sufefd/issue/44924/454514>
Chicago Öztürk, M. , Ermurat, Y. "Escherichia coli’de Yenibileşenli İnterferon beta Salgılanmasında Sinyal Peptidi Kullanımı Üzerine bir Derleme". Selçuk Üniversitesi Fen Fakültesi Fen Dergisi 45 (2019 ): 10-21
RIS TY - JOUR T1 - Escherichia coli’de Yenibileşenli İnterferon beta Salgılanmasında Sinyal Peptidi Kullanımı Üzerine bir Derleme AU - Mehmet Öztürk , Yakup Ermurat Y1 - 2019 PY - 2019 N1 - DO - T2 - Selçuk Üniversitesi Fen Fakültesi Fen Dergisi JF - Journal JO - JOR SP - 10 EP - 21 VL - 45 IS - 1 SN - -2458-9411 M3 - UR - Y2 - 2018 ER -
EndNote %0 Selçuk Üniversitesi Fen Fakültesi Fen Dergisi Escherichia coli’de Yenibileşenli İnterferon beta Salgılanmasında Sinyal Peptidi Kullanımı Üzerine bir Derleme %A Mehmet Öztürk , Yakup Ermurat %T Escherichia coli’de Yenibileşenli İnterferon beta Salgılanmasında Sinyal Peptidi Kullanımı Üzerine bir Derleme %D 2019 %J Selçuk Üniversitesi Fen Fakültesi Fen Dergisi %P -2458-9411 %V 45 %N 1 %R %U
ISNAD Öztürk, Mehmet , Ermurat, Yakup . "Escherichia coli’de Yenibileşenli İnterferon beta Salgılanmasında Sinyal Peptidi Kullanımı Üzerine bir Derleme". Selçuk Üniversitesi Fen Fakültesi Fen Dergisi 45 / 1 (Nisan 2019): 10-21 .
AMA Öztürk M. , Ermurat Y. Escherichia coli’de Yenibileşenli İnterferon beta Salgılanmasında Sinyal Peptidi Kullanımı Üzerine bir Derleme. sufefd. 2019; 45(1): 10-21.
Vancouver Öztürk M. , Ermurat Y. Escherichia coli’de Yenibileşenli İnterferon beta Salgılanmasında Sinyal Peptidi Kullanımı Üzerine bir Derleme. Selçuk Üniversitesi Fen Fakültesi Fen Dergisi. 2019; 45(1): 10-21.
IEEE M. Öztürk ve Y. Ermurat , "Escherichia coli’de Yenibileşenli İnterferon beta Salgılanmasında Sinyal Peptidi Kullanımı Üzerine bir Derleme", Selçuk Üniversitesi Fen Fakültesi Fen Dergisi, c. 45, sayı. 1, ss. 10-21, Nis. 2019


Selçuk Üniversitesi Fen Fakültesi Adına Dekan Prof. Dr. Semahat KÜÇÜKKOLBAŞI
Selçuk Üniversitesi Fen Fakültesi Fen Dergisi temel bilimlerde ve diğer uygulamalı bilimlerde özgün sonuçları olan Türkçe ve İngilizce makaleleri kabul eder. Dergide ayrıca güncel yenilikleri içeren derlemelere de yer verilebilir.
Selçuk Üniversitesi Fen Fakültesi Fen Dergisi;
İlk olarak 1981 yılında S.Ü. Fen-Edebiyat Fakültesi Dergisi olarak yayın hayatına başlamış; 1984 yılına kadar (Sayı 1-4) bu adla yayınlanmıştır.
1984 yılında S.Ü. Fen-Edeb. Fak. Fen Dergisi olarak adı değiştirilmiş 5. sayıdan itibaren bu isimle yayınlanmıştır.
3 Aralık 2008 tarih ve 27073 sayılı Resmi Gazetede yayımlanan 2008/4344 sayılı Bakanlar Kurulu Kararı ile Fen-Edebiyat Fakültesi; Fen Fakültesi ve Edebiyat Fakültesi olarak ayrılınca 2009 yılından itibaren dergi Fen Fakültesi Fen Dergisi olarak çıkmıştır.


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