The biosynthesis of glycoconjugates in bacteria and eukaryotic cells involves the formation of lipid-linked sugar precursors.
The lipid component is a polyisoprenyl-phosphate (undecaprenyl phosphate in bacteria, and dolichyl-P in eukaryotes and Archaea).
All cell types employ phosphoisoprenol-linked saccharides in the early stages of protein glycosylation, as well as for the synthesis of
bacterial cell wall and surface polysaccharides. Nucleotide sugars, which donate carbohydrates for the synthesis of the saccharide moiety,
are available as soluble molecules in cytosolic compartments, while polyisoprenyl-phosphates are embedded in the lipid membrane
bilayer. Once assembled, phosphoisoprenol-linked saccharide molecules must cross the lipid bilayer for further processing. Thus,
transmembrane movement of phosphoisoprenol-linked saccharides is an obligatory, conserved step of significant biologic importance in
all cells, which requires the assistance of membrane proteins known as flippases or translocases. The bacterial lipopolysaccharide
consists of a lipid A-core oligosaccharide (OS) capped in many bacteria by an O-antigen polysaccharide. The O antigen is synthesized
and assembled as a phosphoisoprenyl-linked saccharide. To date, the membrane flippases or translocases involved in O-antigen assembly
can be broadly separated into two groups. One group utilizes ATP hydrolysis for the membrane translocation step, while the other operates
in an ATP hydrolysis-independent fashion. Based on this, up to four different assembly pathways for the O-antigen polysaccharides
are currently recognized. Additional proteins to those involved in the membrane translocation step are also required in each system to
properly catalyze the assembly of the O-antigen polysaccharide, which ultimately becomes the substrate for the ligation reaction with the
lipid A-core OS. Here, we provide a review of all of the different types of membrane flippases involved in the export of LPS O antigen
Keywords: Wzx, Wzk, MsbA, undecaprenyl-phosphate, ligase, glycosylation, polysaccharide export, ABC transporter, synthase, outer membrane,
inner membrane, glycosyltransferases.
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