Highly efficient production of peptides: N-glycosidase F for N-glycomics analysis

Protein Expr Purif. 2014 May:97:17-22. doi: 10.1016/j.pep.2014.02.004. Epub 2014 Feb 26.

Abstract

Peptide: N-glycosidase F (PNGase F) is an asparagine amidase produced by Flavobacterium meningosepticum that serves as a useful tool in the research on protein N-glycosylation. However, native PNGase F purified from F. meningosepticum and recombinant PNGase F expressed in Escherichia coli are obtained only at low levels, with the culture yield being no more than 15mg/L. Here, we report the efficient production of large amounts of recombinant PNGase F. First, a codon-optimized sequence encoding F. meningosepticum PNGase F was cloned into the pPICZaA vector, which was used to transform Pichia pastoris GS115. Clones were screened directly by dot blotting with an anti-6His-tag antibody, and then protein expression was induced in glass tubes to conduct validation assays. The clone expressing the highest level of PNGase F was selected for fermentation at a 5-L scale, and then the recombinant enzyme produced was purified in a single step using affinity chromatography, which yielded 800mg of the protein per liter of culture. The partly glycosylated recombinant PNGase F exhibited an identical specific activity as commercially available PNGase F when using RNase B or other N-glycoproteins as substrates. Thus, the method developed in this study can facilitate the large-scale production and use of PNGase F in the rapidly developing research field of N-glycomics.

Keywords: Deglycosylation activity; F. meningosepticum; N-Glycomics; Peptide: N-glycosidase F (PNGase F); Pichia pastoris.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / isolation & purification
  • Bacterial Proteins / metabolism
  • Base Sequence
  • Cloning, Molecular
  • Flavobacterium / enzymology*
  • Flavobacterium / genetics
  • Glycomics
  • Glycosylation
  • Molecular Sequence Data
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / chemistry
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / genetics*
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / isolation & purification
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / metabolism
  • Pichia / genetics*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism

Substances

  • Bacterial Proteins
  • Recombinant Proteins
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase