One-step immobilization and purification of genetic engineering CBD fusion EndoS on cellulose for antibodies Fc-glycan remodeling

Bioorg Chem. 2019 Oct:91:103114. doi: 10.1016/j.bioorg.2019.103114. Epub 2019 Jul 12.

Abstract

The endoglycosidase (EndoS and its glycosynthase mutants D233A, D233Q) gene was fused with cellulose binding domain (CBD) using pET-35b vector and the fusion enzymes were successfully expressed in Escherichia coli. Then a simplified approach for one-step immobilization and purification of EndoS enzymes using cellulose as matrices were developed and excellent loading efficiency (81-90%) was achieved in optimal condition. The cellulose immobilized CBD-EndoS and the glycosynthase mutants presented high catalytic activity and were successfully applied in a two-step antibody Fc N-glycan remodeling, generating a therapeutic antibody with homogeneous glycoform in high efficiency. The cellulose immobilized CBD-EndoS and its mutants (D233A and D233Q) displayed excellent storage stability when stored at 4 degrees for one month. Reusability studies demonstrated that the cellulose immobilized CBD-EndoS and its mutants could be recycled for five times without obvious activity loss.

Keywords: Antibody glycan remodeling; Cellulose; Cellulose binding domain (CBD); Endoglycosidase; Immobilization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cellulose / genetics*
  • Cellulose / isolation & purification
  • Cellulose / metabolism
  • Enzymes, Immobilized / genetics
  • Enzymes, Immobilized / isolation & purification
  • Enzymes, Immobilized / metabolism
  • Genetic Engineering*
  • Glycoside Hydrolases / genetics
  • Glycoside Hydrolases / isolation & purification
  • Glycoside Hydrolases / metabolism*
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / metabolism*
  • Models, Molecular
  • Molecular Conformation
  • Mutation
  • Polysaccharides / genetics
  • Polysaccharides / metabolism*

Substances

  • Enzymes, Immobilized
  • Immunoglobulin Fc Fragments
  • Polysaccharides
  • Cellulose
  • Glycoside Hydrolases