دورية أكاديمية
A Markov model of glycosylation elucidates isozyme specificity and glycosyltransferase interactions for glycoengineering
| العنوان: | A Markov model of glycosylation elucidates isozyme specificity and glycosyltransferase interactions for glycoengineering |
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| المؤلفون: | Liang, Chenguang, Chiang, Austin W. T., Hansen, Anders H., Arnsdorf, Johnny, Schoffelen, Sanne, Sorrentino, James T., Kellman, Benjamin P., Bao, Bokan, Voldborg, Bjørn G., Lewis, Nathan E. |
| المصدر: | Liang , C , Chiang , A W T , Hansen , A H , Arnsdorf , J , Schoffelen , S , Sorrentino , J T , Kellman , B P , Bao , B , Voldborg , B G & Lewis , N E 2020 , ' A Markov model of glycosylation elucidates isozyme specificity and glycosyltransferase interactions for glycoengineering ' , Current Research in Biotechnology , vol. 2 , pp. 22-36 . https://doi.org/10.1016/j.crbiot.2020.01.001Test |
| سنة النشر: | 2020 |
| المجموعة: | Technical University of Denmark: DTU Orbit / Danmarks Tekniske Universitet |
| مصطلحات موضوعية: | Glycosylation model, Glycomics, Systems glycobiology, Glycoengineering, Isozyme specificity, Glycosyltransferase interactions |
| الوصف: | Glycosylated biopharmaceuticals are important in the global pharmaceutical market. Despite the importance of their glycan structures, our limited knowledge of the glycosylation machinery still hinders controllability of this critical quality attribute. To facilitate discovery of glycosyltransferase specificity and predict glycoengineering efforts, here we extend the approach to model N-linked protein glycosylation as a Markov process. Our model leverages putative glycosyltransferase (GT) specificity to define the biosynthetic pathways for all measured glycans, and the Markov chain modelling is used to learn glycosyltransferase isoform activities and predict glycosylation following glycosyltransferase knock-in/knockout. We apply our methodology to four different glycoengineered therapeutics (i.e., Rituximab, erythropoietin, Enbrel, and alpha-1 antitrypsin) produced in CHO cells. Our model accurately predicted N-linked glycosylation following glycoengineering and further quantified the impact of glycosyltransferase mutations on reactions catalyzed by other glycosyltransferases. By applying these learned GT-GT interaction rules identified from single glycosyltransferase mutants, our model further predicts the outcome of multi-gene glycosyltransferase mutations on the diverse biotherapeutics. Thus, this modeling approach enables rational glycoengineering and the elucidation of relationships between glycosyltransferases, thereby facilitating biopharmaceutical research and aiding the broader study of glycosylation to elucidate the genetic basis of complex changes in glycosylation. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://orbit.dtu.dk/en/publications/74da1088-d9ca-45bb-bcfb-73e554d9af88Test |
| DOI: | 10.1016/j.crbiot.2020.01.001 |
| الإتاحة: | https://doi.org/10.1016/j.crbiot.2020.01.001Test https://orbit.dtu.dk/en/publications/74da1088-d9ca-45bb-bcfb-73e554d9af88Test https://backend.orbit.dtu.dk/ws/files/235837502/1_s2.0_S2590262820300010_main.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.8B0B9C2F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.crbiot.2020.01.001 |
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