Cell wall (Peptidoglycan synthesis)
PG synthesis is important because:
– To provide cell wall structure for protecting the cell from cell lysis (burst) due to high osmotic pressure
– To provide cell wall structure to maintain the shape of cell
– To replace old/matured or spliced PG during cell division
For details, refer to:
– occurs at 3 different locations
1) Cytoplasm – efficient to do it here since many of the biosynthesis precursor molecules are found here (central metabolism occurs mainly in cytoplasm)
2) Cytoplasmic membrane – to deliver newly synthesized PG molecule after assembly
3) External side of cytoplasmic membrane (Cell wall) – to incorporate newly assembled PG molecule to existing cell wall (peptidoglycan structure)
General steps of peptidoglycan synthesis
1) In cytoplasm production of UDP-GlcNAc
– Adding amino group to fructose-6-phosphate produces glucosamine-1-phosphate using
– Adding acetyl-CoA to glucosamine-1-phosphate produces N-acetylglucosamine (NAG/GlcNAc)
– Finally, add UTP (uridine triphosphate) to N-acetylglucosamine produces
– Once UDP-GlcNAc is synthesized, cell can synthesize UDP-MurNAc (N-acetylmuramic acid)
by adding lactose using ether linkage on UDP-GlcNAc.
– Then add five peptides to UDP-MurNAc to make UDP-MurNAc pentapeptide precursor.
2) At internal side of cytoplasmic membrane, assembly occurs
– UDP-MurNAc pentapeptide is added to undecaprenyl pyrophosphate (transport lipid) to produce lipid I.
– Then lipid I is converted to lipid II after addition of GlcNAc from UDP-GlcNAc (UDP removed to provide energy for bonding)
– 5 glycine amino acids bind to lipid II. Once lipid II is ready, it is flipped to the external side of the cytoplasmic membrane, entering to cell wall structure.
– With the help of Penicillin-binding proteins (PBPs – found that penicillin binds here), lipid II is added to the nascent PG.
3) At the external side of cytoplasmic membrane, cross-linking occurs
– Polymerization and cross-linking of glycan strands occurs here with the help of PBP
(PBP aka DD-transpeptidases (DD-TPases), helpscrosslinking of peptides)
– Transglycosylation and transpeptidation reaction occurs to allow cross-linking of PG.
– and Voila! Cell just made/added new peptidoglycan structure.
*Transpeptidation reaction helps cell to incorporate new PG molecules to nascent PG.
For details, refer to:
Pinho, M. G. Kjos, M. and Weening, J. Nat. Rev. Microbiol. (2013) 11: p. 601-614.