Figure 1.

Summary of the main steps of PG synthesis. PG synthesis begins with a series of steps in the cytoplasm. The initial PG precursor, UDP-GlcNAc, is formed from F6P via the hexosamine pathway. UDP-MurNAc is then synthesized from UDP-GlcNAc by the enzymes MurA and MurB. Successive addition of five amino acids forms UDP-MurNAc-pentapeptide. The subsequent steps of PG synthesis take place on the inner face of the cytoplasmic membrane. MraY catalyzes the combination of UDP-MurNAc-pentapeptide with UndP to form Lipid-I, which is then modified by the transfer of UDP-GlcNAc to the MurNAc unit to form Lipid-II by MurG. Flippase MurJ facilitates the translocation of Lipid-II across the cytoplasmic membrane. On the external face of the membrane, GTases and TPases utilize the disaccharide pentapeptide of Lipid-II as a substrate for PG polymerization and synthesis of the PG layer (sacculus) in the periplasm (Gram-negative) or exterior (Gram-positive) of the cell. UndPP, released during PG synthesis, is dephosphorylated by membrane phosphatases (such as BacA, YbjG, PgpB, and LpxT in E. coli or UppP and BcrC in B. subtilis), and the resulting UndP is recycled to the cytoplasm by the UndP transporter UptA of the DedA superfamily, found in both B. subtilis and E. coli.