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Metabolic engineering v.44, 2017년, pp.293 - 301   SCIE
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A biosynthetic route for polysialylating proteins in Escherichia coli

Keys, Timothy G.    (Institute of Microbiology, Department of Biology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland   ); Wetter, Michael    (LimmaTech Biologics AG, Schlieren, Switzerland   ); Hang, Ivan    (Institute of Microbiology, Department of Biology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland   ); Rutschmann, Christoph    (LimmaTech Biologics AG, Schlieren, Switzerland   ); Russo, Simona    (LimmaTech Biologics AG, Schlieren, Switzerland   ); Mally, Manuela    (LimmaTech Biologics AG, Schlieren, Switzerland   ); Steffen, Michael    (LimmaTech Biologics AG, Schlieren, Switzerland   ); Zuppiger, Matthias    (LimmaTech Biologics AG, Schlieren, Switzerland   ); Müller, Fabian    (LimmaTech Biologics AG, Schlieren, Switzerland   ); Schneider, Jörg    (LimmaTech Biologics AG, Schlieren, Switzerland   ); Faridmoayer, Amirreza    (LimmaTech Biologics AG, Schlieren, Switzerland   ); Lin, Chia-wei    (Institute of Microbiology, Department of Biology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland   ); Aebi, Markus    (Institute of Microbiology, Department of Biology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland  );
  • 초록  

    Abstract Polysialic acid (polySia) is a posttranslational modification found on only a handful of proteins in the central nervous and immune systems. The addition of polySia to therapeutic proteins improves pharmacokinetics and reduces immunogenicity. To date, polysialylation of therapeutic proteins has only been achieved in vitro by chemical or chemoenzymatic strategies. In this work, we develop a biosynthetic pathway for site-specific polysialylation of recombinant proteins in the cytoplasm of Escherichia coli . The pathway takes advantage of a bacterial cytoplasmic polypeptide-glycosyltransferase to establish a site-specific primer on the target protein. The glucose primer is extended by glycosyltransferases derived from lipooligosaccharide, lipopolysaccharide and capsular polysaccharide biosynthesis from different bacterial species to synthesize long chain polySia. We demonstrate the new biosynthetic route by modifying green fluorescent proteins and a therapeutic DARPin (designed ankyrin repeat protein). Highlights An orthogonal pathway for N-linked glycosylation of proteins in E. coli . Proteins targeted for glycosylation by introducing a 3-amino acid (N-x-S/T) sequon. Bacterial glycosyltransferases used to modify proteins with a human polysaccharide. First biosynthetic pathway for polysialylation of recombinant proteins. Polysialylation of a therapeutic DARPin increases hydrodynamic volume by 30-fold. Graphical abstract [DISPLAY OMISSION]


  • 주제어

    Glycoengineering .   N-glycosyltransferase .   Polysialic acid .   DARPin .   Stealth polymer.  

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