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  • 标题:A gene responsible for prolyl-hydroxylation of moss-produced recombinant human erythropoietin
  • 本地全文:下载
  • 作者:Juliana Parsons ; Friedrich Altmann ; Manuela Graf
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2013
  • 卷号:3
  • 期号:1
  • DOI:10.1038/srep03019
  • 语种:English
  • 出版社:Springer Nature
  • 摘要:Recombinant production of pharmaceutical proteins is crucial, not only for personalized medicine. While most biopharmaceuticals are currently produced in mammalian cell culture, plant-made pharmaceuticals gain momentum. Post-translational modifications in plants are similar to those in humans, however, existing differences may affect quality, safety and efficacy of the products. A frequent modification in higher eukaryotes is prolyl-4-hydroxylase (P4H)-catalysed prolyl-hydroxylation. P4H sequence recognition sites on target proteins differ between humans and plants leading to non-human posttranslational modifications of recombinant human proteins produced in plants. The resulting hydroxyprolines display the anchor for plant-specific O-glycosylation, which bears immunogenic potential for patients. Here we describe the identification of a plant gene responsible for non-human prolyl-hydroxylation of human erythropoietin (hEPO) recombinantly produced in plant (moss) bioreactors. Targeted ablation of this gene abolished undesired prolyl-hydroxylation of hEPO and thus paves the way for plant-made pharmaceuticals humanized via glyco-engineering in moss bioreactors.
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