Analogies and homologies in lipopolysaccharide and glycoprotein biosynthesis in bacteria

Isabelle Hug, Mario F. Feldman

Research output: Contribution to journalReview article

87 Scopus citations

Abstract

Bacteria generate and attach countless glycan structures to diverse macromolecules. Despite this diversity, the mechanisms of glycoconjugate biosynthesis are often surprisingly similar. The focus of this review is on thecommonalities between lipopolysaccharide (LPS) and glycoprotein assembly pathways and their evolutionary relationship. Three steps that are essential for both pathways are completed by membrane proteins. These include the initiation of glycan assembly through the attachment of a first sugar residue onto the lipid carrier undecaprenyl pyrophosphate, the translocation acrossthe plasma membrane and the final transfer onto proteins or lipid A-core. Two families of initiating enzymes have been described: the polyprenyl-P N-acetylhexosamine-1-P transferases and the polyprenyl-P hexosamine-1-P transferases, represented by Escherichia coli WecA and Salmonella enterica WbaP, respectively. Translocases are either Wzx-like flippases or adenosine triphosphate (ATP)-binding cassette transporters (ABC transporters). The latter can consist either of two polypeptides, Wzt and Wzm, or of a single polypeptide homolog to the Campylobacter jejuni PglK. Finally, there are two families of conjugating enzymes, the N-oligosaccharyltransferases (N-OTase), best represented by C. jejuni PglB, and the O-OTases, including Neisseria meningitidis PglL and the O antigen ligases involved in LPS biosynthesis. With the exception of the N-OTases, probably restricted to glycoprotein synthesis, members of all these transmembrane protein families can be involved in the synthesis of both glycoproteins and LPS. Because many translocation and conjugation enzymes display relaxed substrate specificity, these bacterial enzymes could be exploited in engineered living bacteria for customized glycoconjugate production, generating potential vaccines and therapeutics.

Original languageEnglish
Pages (from-to)138-151
Number of pages14
JournalGlycobiology
Volume21
Issue number2
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

Keywords

  • Flippase
  • Glycosylation
  • LigaseLipopolysaccharide
  • Oligosaccharyltransferase

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