Derleme
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Laktik Asit Bakterilerinde CRISPR/Cas Sisteminin Biyoteknoloji ve Genetik Mühendisliğinde Kullanımı

Yıl 2020, Cilt: 18 Sayı: 3, 303 - 311, 29.10.2020
https://doi.org/10.24323/akademik-gida.818183

Öz

Laktik asit bakterileri (LAB) düşük GC içeriğine sahip, Gram pozitif, spor oluşturmayan, hareketsiz, fakültatif anaerob, asidik ortama dayanıklı ve çeşitli besinleri fermente etme yeteneğindeki bakterilerden oluşan bir gruptur. Bu grup genellikle probiyotik ve starter kültür olarak kullanılan bakterileri içerir. “Düzenli aralıklarla kümelenmiş kısa palindromik tekrarlar (CRISPR)” ve “CRISPR ilişkili Cas proteinleri”den oluşan CRISPR/Cas sisteminin keşfi ile bu konuda yapılan çalışmalar hız kazanmış ve genom düzenlemeleri kolayca yapılmaya başlanmıştır. Söz konusu sistem yardımıyla yapılan genom düzenlemeleri ve sistemin diğer genetik mühendisliği yöntemleriyle birleştirilmesi, LAB’ın ve probiyotiklerin endüstri ve klinikte kullanımına yönelik yeni bir çığır açacaktır. Bu derleme, CRISPR/Cas sisteminin genel işleyişi, LAB’ta hangi sistemlerden oluştuğu, biyoteknoloji ve genetik mühendisliğindeki mevcut uygulamaları ile gelecekteki potansiyel uygulamaları konusunda geniş bir bakış açısı sağlayacaktır.

Kaynakça

  • [1] Nethery, M.A., Henriksen, E.D., Daughtry, K.V., Johanningsmeier, S.D., Barrangou, R. (2019). Comparative genomics of eight Lactobacillus buchneri strains isolated from food spoilage. BMC Genomics, 20, 1–12.
  • [2] Stout, E., Klaenhammer, T., Barrangou, R. (2017). CRISPR-Cas technologies and applications in food bacteria. Annual Review of Food Science and Technology, 8, 413–437.
  • [3] Sanozky-Dawes, R., Selle, K., O’Flaherty, S., Klaenhammer, T., Barrangou, R. (2015). Occurrence and activity of a type II CRISPR-Cas system in Lactobacillus gasseri. Microbiology (United Kingdom), 161, 1752–1761.
  • [4] Gümüş, N., Tezcanlı Kaymaz, B. (2018). CRISPR/Cas9 Age in Genome Editing and Leukemia Applications. Kafkas Journal of Medical Sciences, 8, 232–248.
  • [5] Horvath, P., Coûté-Monvoisin, A.C., Romero, D.A., Boyaval, P., Fremaux, C., Barrangou, R. (2009). Comparative analysis of CRISPR loci in lactic acid bacteria genomes. International Journal of Food Microbiology, 131, 62–70.
  • [6] Börner, R.A., Kandasamy, V., Axelsen, A.M., Nielsen, A.T., Bosma, E.F. (2019). Genome editing of lactic acid bacteria: Opportunities for food, feed, pharma and biotech. FEMS Microbiology Letters, 366, 1–12.
  • [7] Yörük, G.N., Güner, A. (2010). Laktik asit bakterilerinin sınıflandırılması ve Weissella türlerinin gıda mikrobiyolojisinde önemi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 6, 163–176.
  • [8] Yao, R., Liu, D., Jia, X., Zheng, Y., Liu, W., Xiao, Y. (2018). CRISPR-Cas9/Cas12a biotechnology and application in bacteria. Synthetic and Systems Biotechnology, 3, 135–149.
  • [9] Roberts, A., Barrangou, R. (2020). Applications of CRISPR-Cas systems in lactic acid bacteria. FEMS Microbiology Reviews, 1–15.
  • [10] Hidalgo-Cantabrana, C., O’Flaherty, S., Barrangou, R. (2017). CRISPR-Based engineering of next-generation lactic acid bacteria. Current Opinion in Microbiology, 37, 79–87.
  • [11] Pijkeren, J.P., Van, Barrangou, R. (2018). Genome editing of food-grade lactobacilli to develop therapeutic probiotics. Bugs as Drugs, 5, 389–408.
  • [12] Pan, M., Barrangou, R. (2020). Combining omics technologies with CRISPR-based genome editing to study food microbes. Current Opinion in Biotechnology, 61, 198–208.
  • [13] Hao, M., Cui, Y., Qu, X. (2018). Analysis of CRISPR-cas system in Streptococcus thermophilus and its application. Frontiers in Microbiology, 9, 1–7.
  • [14] Barrangou, R., Dudley, E.G. (2016). CRISPR-Based typing and next-generation tracking technologies. Annual Review of Food Science and Technology, 7, 395–411.
  • [15] Golubov, A. (2016). Chapter6: CRISPR: Bacteria Immune System. In Genome Stability: From Virus to Human Application. Elsevier Inc. 87-96.
  • [16] Alkhnbashi, O.S., Meier, T., Mitrofanov, A., Backofen, R., Voß, B. (2020). CRISPR-Cas bioinformatics. In Methods, 172, 3-11.
  • [17] Barrangou, R., Marraffini, L.A. (2014). CRISPR-cas systems: Prokaryotes upgrade to adaptive immunity. In Molecular Cell, 54, 234-244.
  • [18] Crawley, A.B., Henriksen, E.D., Stout, E., Brandt, K., Barrangou, R. (2018). Characterizing the activity of abundant, diverse and active CRISPR-Cas systems in lactobacilli. Scientific Reports, 8, 1-12.
  • [19] Common, J., Morley, D., Westra, E.R., Van Houte, S. (2019). CRISPR-Cas immunity leads to a coevolutionary arms race between Streptococcus thermophilus and lytic phage. Philosophical Transactions of the Royal Society B: Biological Sciences, 374, 1-11.
  • [20] Hidalgo-Cantabrana, C., Goh, Y.J., Pan, M., Sanozky-Dawes, R., Barrangou, R. (2019). Genome editing using the endogenous type I CRISPR-Cas system in Lactobacillus crispatus. Proceedings of the National Academy of Sciences of the United States of America, 116, 15774–15783.
  • [21] McGinn, J., Marraffini, L.A. (2019). Molecular mechanisms of CRISPR–Cas spacer acquisition. Nature Reviews Microbiology, 17, 7–12.
  • [22] Makarova, K.S., Haft, D.H., Barrangou, R., Brouns, S.J.J., Charpentier, E., Horvath, P., Moineau, S., Mojica, F.J.M., Wolf, Y.I., Yakunin, A.F., Van Der Oost, J., Koonin, E.V. (2011). Evolution and classification of the CRISPR-Cas systems. Nature Reviews Microbiology, 9, 467–477.
  • [23] Nethery, M.A., Barrangou, R. (2019). Predicting and visualizing features of CRISPR–Cas systems. In Methods in Enzymology (1st ed., Vol. 616). Elsevier Inc.
  • [24] Grissa, I., Vergnaud, G., Pourcel, C. (2007). CRISPRFinder: A web tool to identify clustered regularly interspaced short palindromic repeats. Nucleic Acids Research, 35, 52–57.
  • [25] Aydin, S., Personne, Y., Newire, E., Laverick, R., Russell, O., Roberts, A.P., Enne, V.I. (2017). Presence of Type I-F CRISPR/Cas systems is associated with antimicrobial susceptibility in Escherichia coli. Journal of Antimicrobial Chemotherapy, 72, 2213–2218.
  • [26] Leenay, R.T., Vento, J.M., Shah, M., Martino, M.E., Leulier, F., Beisel, C.L. (2019). Genome editing with CRISPR-Cas9 in Lactobacillus plantarum revealed that editing outcomes can vary across strains and between methods. Biotechnology Journal, 14, 1–11.
  • [27] Plavec, T.V., Berlec, A. (2020). Safety Aspects of Genetically Modified Lactic Acid Bacteria. Microorganisms, 8, 297.
  • [28] Peters, J.M., Koo, B.M., Patino, R., Heussler, G.E., Hearne, C.C., Qu, J., Inclan, Y.F., Hawkins, J.S., Lu, C.H.S., Silvis, M.R., Harden, M.M., Osadnik, H., Peters, J.E., Engel, J.N., Dutton, R.J., Grossman, A.D., Gross, C.A., Rosenberg, O.S. (2019). Enabling genetic analysis of diverse bacteria with Mobile-CRISPRi. Nature Microbiology, 4, 244–250.
  • [29] Xiong, Z.Q., Wei, Y.Y., Kong, L.H., Song, X., Yi, H.X., Ai, L.Z. (2020). Short communication: An inducible CRISPR/dCas9 gene repression system in Lactococcus lactis. Journal of Dairy Science, 103, 161–165.
  • [30] Muysson, J., Miller, L., Allie, R., Inglis, D.L. (2019). The Use of CRISPR-Cas9 Genome Editing to Determine the Importance of Glycerol Uptake in Wine Yeast During Icewine Fermentation. Fermentation, 5, 1-15.
  • [31] Song, X., Huang, H., Xiong, Z., Ai, L., Yang, S. (2017). CRISPR-Cas9D10A Nickase-Assisted Genome Editing in Lactobacillus casei. 83, 1–14.
  • [32] Oh, J.H., Van Pijkeren, J.P. (2014). CRISPR-Cas9-assisted recombineering in Lactobacillus reuteri. Nucleic Acids Research, 42, 1–11.
  • [33] Stout, E.A., Sanozky-Dawes, R., Goh, Y.J., Crawley, A.B., Klaenhammer, T.R., Barrangou, R. (2018). Deletion-based escape of CRISPR-CAS9 targeting in Lactobacillus gasseri. Microbiology (United Kingdom), 164, 1098–1111.
  • [34] Sundaresan, R., Keilbarth, M.W., Rajan, R., Sundaresan, R., Parameshwaran, H.P., Yogesha, S.D., Keilbarth, M.W., Rajan, R. (2017). RNA-Independent DNA cleavage activities of Cas9 and Cas12a. CellReports, 21, 3728–3739.
  • [35] Huang, H., Song, X., Yang, S. (2019). Development of a RecE/T-Assisted CRISPR–Cas9 Toolbox for Lactobacillus. Biotechnology Journal, 14, 1–12.
  • [36] Els, S. Van Der, James, J.K., Kleerebezem, M., Bron, P.A. (2018). Versatile Cas9-Driven Subpopulation Selection Toolbox for Lactococcus lactis. Applied and Environmental Microbiology, 84(8):e02752-17 84.
  • [37] Guo, T., Xin, Y., Zhang, Y., Gu, X., Kong, J. (2019). A rapid and versatile tool for genomic engineering in Lactococcus lactis. Microbial Cell Factories, 72, 1–12.
  • [38] Briner, A.E., Lugli, G.A., Milani, C., Duranti, S., Turroni, F., Gueimonde, M., Margolles, A., Van Sinderen, D., Ventura, M., Barrangou, R. (2015). Occurrence and diversity of CRISPR-Cas systems in the genus bifidobacterium. PLoS ONE, 10, 1–16.
  • [39] Pan, M., Nethery, M.A., Hidalgo-Cantabrana, C., Barrangou, R. (2020). Comprehensive Mining and Characterization of CRISPR-Cas Systems in Bifidobacterium. Microorganisms, 8, 720.
  • [40] Hidalgo-Cantabrana, C., Crawley, A. B., Sanchez, B., Barrangou, R. (2017). Characterization and exploitation of CRISPR loci in Bifidobacterium longum. Frontiers in Microbiology, 8, 1–16.
  • [41] Bagherpour, G., Ghasemi, H., Zand, B., Zarei, N., Roohvand, F., Ardakani, E.M., Azizi, M., Khalaj, V. (2018). Oral administration of recombinant Saccharomyces boulardii expressing ovalbumin-CPE fusion protein induces antibody response in mice. Frontiers in Microbiology, 9, 1–9.
  • [42] Klaenhammer, T.R. (1991). Development of bacteriophage-resistant strains of lactic acid bacteria. Biochemical Society Transactions, 19, 675–681.
  • [43] Spus, M., Li, M., Alexeeva, S., Wolkers-Rooijackers, J.C.M., Zwietering, M.H., Abee, T., Smid, E.J. (2015). Strain diversity and phage resistance in complex dairy starter cultures. Journal of Dairy Science, 98, 5173–5182.
  • [44] Zhou, D., Jiang, Z., Pang, Q., Zhu, Y., Wang, Q., Qi, Q. (2019). CRISPR/Cas9-assisted seamless genome editing in Lactobacillus plantarum and its application in N-acetylglucosamine production. Applied and Environmental Microbiology, 85, 1–11.
  • [45] Selle, K., Klaenhammer, T.R., Barrangou, R. (2015). CRISPR-based screening of genomic island excision events in bacteria. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 112, 1–6.

Utilization of CRISPR/Cas System of Lactic Acid Bacteria in Biotechnology and Genetic Engineering

Yıl 2020, Cilt: 18 Sayı: 3, 303 - 311, 29.10.2020
https://doi.org/10.24323/akademik-gida.818183

Öz

Lactic acid bacteria (LAB) are a group of low-GC content, Gram-positive, facultative anaerob, non-motile, non-spore-forming, acid tolerant bacteria that can ferment various nutrients. This group of bacteria mostly contains starter cultures and probiotics. Discovery of “Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)” and “CRISPR-related Cas” proteins accelerated studies pertaining to the subject and provided a simplified genom editing mechanism. Genom editing via CRISPR/Cas system and combination of this system with other genetic tools will break new ground on industrial and clinical applications of lactic acid bacteria and probiotics. This review aims to provide an insight on how CRISPR/Cas system works, which types of CRISPR/Cas system lactic acid bacteria and probiotics contain, how it is applied to biotechnology and genetic engineering as well as the future potential applications.

Kaynakça

  • [1] Nethery, M.A., Henriksen, E.D., Daughtry, K.V., Johanningsmeier, S.D., Barrangou, R. (2019). Comparative genomics of eight Lactobacillus buchneri strains isolated from food spoilage. BMC Genomics, 20, 1–12.
  • [2] Stout, E., Klaenhammer, T., Barrangou, R. (2017). CRISPR-Cas technologies and applications in food bacteria. Annual Review of Food Science and Technology, 8, 413–437.
  • [3] Sanozky-Dawes, R., Selle, K., O’Flaherty, S., Klaenhammer, T., Barrangou, R. (2015). Occurrence and activity of a type II CRISPR-Cas system in Lactobacillus gasseri. Microbiology (United Kingdom), 161, 1752–1761.
  • [4] Gümüş, N., Tezcanlı Kaymaz, B. (2018). CRISPR/Cas9 Age in Genome Editing and Leukemia Applications. Kafkas Journal of Medical Sciences, 8, 232–248.
  • [5] Horvath, P., Coûté-Monvoisin, A.C., Romero, D.A., Boyaval, P., Fremaux, C., Barrangou, R. (2009). Comparative analysis of CRISPR loci in lactic acid bacteria genomes. International Journal of Food Microbiology, 131, 62–70.
  • [6] Börner, R.A., Kandasamy, V., Axelsen, A.M., Nielsen, A.T., Bosma, E.F. (2019). Genome editing of lactic acid bacteria: Opportunities for food, feed, pharma and biotech. FEMS Microbiology Letters, 366, 1–12.
  • [7] Yörük, G.N., Güner, A. (2010). Laktik asit bakterilerinin sınıflandırılması ve Weissella türlerinin gıda mikrobiyolojisinde önemi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 6, 163–176.
  • [8] Yao, R., Liu, D., Jia, X., Zheng, Y., Liu, W., Xiao, Y. (2018). CRISPR-Cas9/Cas12a biotechnology and application in bacteria. Synthetic and Systems Biotechnology, 3, 135–149.
  • [9] Roberts, A., Barrangou, R. (2020). Applications of CRISPR-Cas systems in lactic acid bacteria. FEMS Microbiology Reviews, 1–15.
  • [10] Hidalgo-Cantabrana, C., O’Flaherty, S., Barrangou, R. (2017). CRISPR-Based engineering of next-generation lactic acid bacteria. Current Opinion in Microbiology, 37, 79–87.
  • [11] Pijkeren, J.P., Van, Barrangou, R. (2018). Genome editing of food-grade lactobacilli to develop therapeutic probiotics. Bugs as Drugs, 5, 389–408.
  • [12] Pan, M., Barrangou, R. (2020). Combining omics technologies with CRISPR-based genome editing to study food microbes. Current Opinion in Biotechnology, 61, 198–208.
  • [13] Hao, M., Cui, Y., Qu, X. (2018). Analysis of CRISPR-cas system in Streptococcus thermophilus and its application. Frontiers in Microbiology, 9, 1–7.
  • [14] Barrangou, R., Dudley, E.G. (2016). CRISPR-Based typing and next-generation tracking technologies. Annual Review of Food Science and Technology, 7, 395–411.
  • [15] Golubov, A. (2016). Chapter6: CRISPR: Bacteria Immune System. In Genome Stability: From Virus to Human Application. Elsevier Inc. 87-96.
  • [16] Alkhnbashi, O.S., Meier, T., Mitrofanov, A., Backofen, R., Voß, B. (2020). CRISPR-Cas bioinformatics. In Methods, 172, 3-11.
  • [17] Barrangou, R., Marraffini, L.A. (2014). CRISPR-cas systems: Prokaryotes upgrade to adaptive immunity. In Molecular Cell, 54, 234-244.
  • [18] Crawley, A.B., Henriksen, E.D., Stout, E., Brandt, K., Barrangou, R. (2018). Characterizing the activity of abundant, diverse and active CRISPR-Cas systems in lactobacilli. Scientific Reports, 8, 1-12.
  • [19] Common, J., Morley, D., Westra, E.R., Van Houte, S. (2019). CRISPR-Cas immunity leads to a coevolutionary arms race between Streptococcus thermophilus and lytic phage. Philosophical Transactions of the Royal Society B: Biological Sciences, 374, 1-11.
  • [20] Hidalgo-Cantabrana, C., Goh, Y.J., Pan, M., Sanozky-Dawes, R., Barrangou, R. (2019). Genome editing using the endogenous type I CRISPR-Cas system in Lactobacillus crispatus. Proceedings of the National Academy of Sciences of the United States of America, 116, 15774–15783.
  • [21] McGinn, J., Marraffini, L.A. (2019). Molecular mechanisms of CRISPR–Cas spacer acquisition. Nature Reviews Microbiology, 17, 7–12.
  • [22] Makarova, K.S., Haft, D.H., Barrangou, R., Brouns, S.J.J., Charpentier, E., Horvath, P., Moineau, S., Mojica, F.J.M., Wolf, Y.I., Yakunin, A.F., Van Der Oost, J., Koonin, E.V. (2011). Evolution and classification of the CRISPR-Cas systems. Nature Reviews Microbiology, 9, 467–477.
  • [23] Nethery, M.A., Barrangou, R. (2019). Predicting and visualizing features of CRISPR–Cas systems. In Methods in Enzymology (1st ed., Vol. 616). Elsevier Inc.
  • [24] Grissa, I., Vergnaud, G., Pourcel, C. (2007). CRISPRFinder: A web tool to identify clustered regularly interspaced short palindromic repeats. Nucleic Acids Research, 35, 52–57.
  • [25] Aydin, S., Personne, Y., Newire, E., Laverick, R., Russell, O., Roberts, A.P., Enne, V.I. (2017). Presence of Type I-F CRISPR/Cas systems is associated with antimicrobial susceptibility in Escherichia coli. Journal of Antimicrobial Chemotherapy, 72, 2213–2218.
  • [26] Leenay, R.T., Vento, J.M., Shah, M., Martino, M.E., Leulier, F., Beisel, C.L. (2019). Genome editing with CRISPR-Cas9 in Lactobacillus plantarum revealed that editing outcomes can vary across strains and between methods. Biotechnology Journal, 14, 1–11.
  • [27] Plavec, T.V., Berlec, A. (2020). Safety Aspects of Genetically Modified Lactic Acid Bacteria. Microorganisms, 8, 297.
  • [28] Peters, J.M., Koo, B.M., Patino, R., Heussler, G.E., Hearne, C.C., Qu, J., Inclan, Y.F., Hawkins, J.S., Lu, C.H.S., Silvis, M.R., Harden, M.M., Osadnik, H., Peters, J.E., Engel, J.N., Dutton, R.J., Grossman, A.D., Gross, C.A., Rosenberg, O.S. (2019). Enabling genetic analysis of diverse bacteria with Mobile-CRISPRi. Nature Microbiology, 4, 244–250.
  • [29] Xiong, Z.Q., Wei, Y.Y., Kong, L.H., Song, X., Yi, H.X., Ai, L.Z. (2020). Short communication: An inducible CRISPR/dCas9 gene repression system in Lactococcus lactis. Journal of Dairy Science, 103, 161–165.
  • [30] Muysson, J., Miller, L., Allie, R., Inglis, D.L. (2019). The Use of CRISPR-Cas9 Genome Editing to Determine the Importance of Glycerol Uptake in Wine Yeast During Icewine Fermentation. Fermentation, 5, 1-15.
  • [31] Song, X., Huang, H., Xiong, Z., Ai, L., Yang, S. (2017). CRISPR-Cas9D10A Nickase-Assisted Genome Editing in Lactobacillus casei. 83, 1–14.
  • [32] Oh, J.H., Van Pijkeren, J.P. (2014). CRISPR-Cas9-assisted recombineering in Lactobacillus reuteri. Nucleic Acids Research, 42, 1–11.
  • [33] Stout, E.A., Sanozky-Dawes, R., Goh, Y.J., Crawley, A.B., Klaenhammer, T.R., Barrangou, R. (2018). Deletion-based escape of CRISPR-CAS9 targeting in Lactobacillus gasseri. Microbiology (United Kingdom), 164, 1098–1111.
  • [34] Sundaresan, R., Keilbarth, M.W., Rajan, R., Sundaresan, R., Parameshwaran, H.P., Yogesha, S.D., Keilbarth, M.W., Rajan, R. (2017). RNA-Independent DNA cleavage activities of Cas9 and Cas12a. CellReports, 21, 3728–3739.
  • [35] Huang, H., Song, X., Yang, S. (2019). Development of a RecE/T-Assisted CRISPR–Cas9 Toolbox for Lactobacillus. Biotechnology Journal, 14, 1–12.
  • [36] Els, S. Van Der, James, J.K., Kleerebezem, M., Bron, P.A. (2018). Versatile Cas9-Driven Subpopulation Selection Toolbox for Lactococcus lactis. Applied and Environmental Microbiology, 84(8):e02752-17 84.
  • [37] Guo, T., Xin, Y., Zhang, Y., Gu, X., Kong, J. (2019). A rapid and versatile tool for genomic engineering in Lactococcus lactis. Microbial Cell Factories, 72, 1–12.
  • [38] Briner, A.E., Lugli, G.A., Milani, C., Duranti, S., Turroni, F., Gueimonde, M., Margolles, A., Van Sinderen, D., Ventura, M., Barrangou, R. (2015). Occurrence and diversity of CRISPR-Cas systems in the genus bifidobacterium. PLoS ONE, 10, 1–16.
  • [39] Pan, M., Nethery, M.A., Hidalgo-Cantabrana, C., Barrangou, R. (2020). Comprehensive Mining and Characterization of CRISPR-Cas Systems in Bifidobacterium. Microorganisms, 8, 720.
  • [40] Hidalgo-Cantabrana, C., Crawley, A. B., Sanchez, B., Barrangou, R. (2017). Characterization and exploitation of CRISPR loci in Bifidobacterium longum. Frontiers in Microbiology, 8, 1–16.
  • [41] Bagherpour, G., Ghasemi, H., Zand, B., Zarei, N., Roohvand, F., Ardakani, E.M., Azizi, M., Khalaj, V. (2018). Oral administration of recombinant Saccharomyces boulardii expressing ovalbumin-CPE fusion protein induces antibody response in mice. Frontiers in Microbiology, 9, 1–9.
  • [42] Klaenhammer, T.R. (1991). Development of bacteriophage-resistant strains of lactic acid bacteria. Biochemical Society Transactions, 19, 675–681.
  • [43] Spus, M., Li, M., Alexeeva, S., Wolkers-Rooijackers, J.C.M., Zwietering, M.H., Abee, T., Smid, E.J. (2015). Strain diversity and phage resistance in complex dairy starter cultures. Journal of Dairy Science, 98, 5173–5182.
  • [44] Zhou, D., Jiang, Z., Pang, Q., Zhu, Y., Wang, Q., Qi, Q. (2019). CRISPR/Cas9-assisted seamless genome editing in Lactobacillus plantarum and its application in N-acetylglucosamine production. Applied and Environmental Microbiology, 85, 1–11.
  • [45] Selle, K., Klaenhammer, T.R., Barrangou, R. (2015). CRISPR-based screening of genomic island excision events in bacteria. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 112, 1–6.
Toplam 45 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Gıda Mühendisliği
Bölüm Derleme Makaleler
Yazarlar

Özge Kahraman Ilıkkan Bu kişi benim 0000-0001-5843-6868

Yayımlanma Tarihi 29 Ekim 2020
Gönderilme Tarihi 30 Ocak 2020
Yayımlandığı Sayı Yıl 2020 Cilt: 18 Sayı: 3

Kaynak Göster

APA Kahraman Ilıkkan, Ö. (2020). Laktik Asit Bakterilerinde CRISPR/Cas Sisteminin Biyoteknoloji ve Genetik Mühendisliğinde Kullanımı. Akademik Gıda, 18(3), 303-311. https://doi.org/10.24323/akademik-gida.818183
AMA Kahraman Ilıkkan Ö. Laktik Asit Bakterilerinde CRISPR/Cas Sisteminin Biyoteknoloji ve Genetik Mühendisliğinde Kullanımı. Akademik Gıda. Ekim 2020;18(3):303-311. doi:10.24323/akademik-gida.818183
Chicago Kahraman Ilıkkan, Özge. “Laktik Asit Bakterilerinde CRISPR/Cas Sisteminin Biyoteknoloji Ve Genetik Mühendisliğinde Kullanımı”. Akademik Gıda 18, sy. 3 (Ekim 2020): 303-11. https://doi.org/10.24323/akademik-gida.818183.
EndNote Kahraman Ilıkkan Ö (01 Ekim 2020) Laktik Asit Bakterilerinde CRISPR/Cas Sisteminin Biyoteknoloji ve Genetik Mühendisliğinde Kullanımı. Akademik Gıda 18 3 303–311.
IEEE Ö. Kahraman Ilıkkan, “Laktik Asit Bakterilerinde CRISPR/Cas Sisteminin Biyoteknoloji ve Genetik Mühendisliğinde Kullanımı”, Akademik Gıda, c. 18, sy. 3, ss. 303–311, 2020, doi: 10.24323/akademik-gida.818183.
ISNAD Kahraman Ilıkkan, Özge. “Laktik Asit Bakterilerinde CRISPR/Cas Sisteminin Biyoteknoloji Ve Genetik Mühendisliğinde Kullanımı”. Akademik Gıda 18/3 (Ekim 2020), 303-311. https://doi.org/10.24323/akademik-gida.818183.
JAMA Kahraman Ilıkkan Ö. Laktik Asit Bakterilerinde CRISPR/Cas Sisteminin Biyoteknoloji ve Genetik Mühendisliğinde Kullanımı. Akademik Gıda. 2020;18:303–311.
MLA Kahraman Ilıkkan, Özge. “Laktik Asit Bakterilerinde CRISPR/Cas Sisteminin Biyoteknoloji Ve Genetik Mühendisliğinde Kullanımı”. Akademik Gıda, c. 18, sy. 3, 2020, ss. 303-11, doi:10.24323/akademik-gida.818183.
Vancouver Kahraman Ilıkkan Ö. Laktik Asit Bakterilerinde CRISPR/Cas Sisteminin Biyoteknoloji ve Genetik Mühendisliğinde Kullanımı. Akademik Gıda. 2020;18(3):303-11.

Cited By

CRISPR/Cas9 Systems and Gene Editing Technology
Osmaniye Korkut Ata Üniversitesi Fen Bilimleri Enstitüsü Dergisi
https://doi.org/10.47495/okufbed.1085220

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Akademik Gıda (Academic Food Journal) is licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0).