Skip to main content
. 2014 Oct 20;5:492. doi: 10.3389/fimmu.2014.00492

Figure 2.

Figure 2

Biosynthesis of lipopolysaccharides in Gram-negative bacteria by the polymerase-dependent pathway. Many steps of the complex sequences and controls in the biosynthesis of LPS in Gram-negative bacteria are similar to those in mammalian glycoprotein biosynthesis. The inner membrane serves as the site of glycan biosynthesis, and the membrane-bound acceptor is undecaprenol-phosphate (P-Und) having 11 isoprenyl units, which is less than those found in eukaryotic Dol. Nucleotide sugars are synthesized in the cytosol and used for most glycosylation reactions. As in the N-glycan biosynthesis, the first sugar is transferred as sugar-phosphate by membrane-bound WecA to synthesize GalNAc/GlcNAc-PP-Und. This step can also be blocked by tunicamycin. It is possible that a 4-epimerase is involved. Subsequently, sugars are added individually to form the repeating unit of the O antigen. The glycosyltransferases that transfer sugars from nucleotide sugars usually have a high specificity for their donor and acceptor substrates and are associated with the membrane. After Wzx transports the repeating units to the periplasm, they are polymerized by Wzy by addition of repeating units to the reducing end of the growing polysaccharide linked to PP-Dol. The O antigen can be further processed and modified to form completed O antigens and the biosynthesis is usually terminated with Wzz. The O polysaccharide is then transferred to a sugar of the core oligosaccharide linked to lipid A by a ligase, forming the LPS, which is exported to the outer membrane by the Lpt complex. The O antigenic polysaccharide is then exposed to the environment on the outer membrane. Although many bacterial enzymes involved in LPS synthesis have been cloned, the individual steps of LPS synthesis are not well understood, mainly because of the major challenge to find the appropriate enzyme substrates and conditions to assay enzymes. The example shows the biosynthesis of the E. coli O104 antigen. The repeating unit tetrasaccharide contains the cancer-associated T antigen (Galβ1-3GalNAc), as well as the sialyl-T antigen (sialylα2-3Galβ1-3GalNAc). The WbwA sialyltransferase and the WbwB Gal-transferase remain to be characterized.