Substitute sweeteners: diverse bacterial oligosaccharyltransferases with unique N-glycosylation site preferences

Sci Rep. 2015 Oct 20:5:15237. doi: 10.1038/srep15237.

Abstract

The central enzyme in the Campylobacter jejuni asparagine-linked glycosylation pathway is the oligosaccharyltransferase (OST), PglB, which transfers preassembled glycans to specific asparagine residues in target proteins. While C. jejuni PglB (CjPglB) can transfer many diverse glycan structures, the acceptor sites that it recognizes are restricted predominantly to those having a negatively charged residue in the -2 position relative to the asparagine. Here, we investigated the acceptor-site preferences for 23 homologs with natural sequence variation compared to CjPglB. Using an ectopic trans-complementation assay for CjPglB function in glycosylation-competent Escherichia coli, we demonstrated in vivo activity for 16 of the candidate OSTs. Interestingly, the OSTs from Campylobacter coli, Campylobacter upsaliensis, Desulfovibrio desulfuricans, Desulfovibrio gigas, and Desulfovibrio vulgaris, exhibited significantly relaxed specificity towards the -2 position compared to CjPglB. These enzymes glycosylated minimal N-X-T motifs in multiple targets and each followed unique, as yet unknown, rules governing acceptor-site preferences. One notable example is D. gigas PglB, which was the only bacterial OST to glycosylate the Fc domain of human immunoglobulin G at its native 'QYNST' sequon. Overall, we find that a subset of bacterial OSTs follow their own rules for acceptor-site specificity, thereby expanding the glycoengineering toolbox with previously unavailable biocatalytic diversity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Computational Biology
  • Data Mining
  • Genome, Bacterial
  • Genomics
  • Glycoproteins / chemistry
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Glycosylation
  • Hexosyltransferases / chemistry
  • Hexosyltransferases / genetics
  • Hexosyltransferases / metabolism
  • Humans
  • Immunoglobulin Fc Fragments / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Models, Molecular
  • Molecular Conformation
  • Phylogeny
  • Polysaccharides
  • Polysaccharides, Bacterial / chemistry
  • Polysaccharides, Bacterial / metabolism
  • Substrate Specificity
  • Sweetening Agents / chemistry*
  • Sweetening Agents / metabolism*

Substances

  • Bacterial Proteins
  • Glycoproteins
  • Immunoglobulin Fc Fragments
  • Membrane Proteins
  • Polysaccharides
  • Polysaccharides, Bacterial
  • Sweetening Agents
  • Hexosyltransferases
  • dolichyl-diphosphooligosaccharide - protein glycotransferase