Peptidoglycan synthesis

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:

Peptidoglycan Structure and Function


Peptidoglycan synthesis


– 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

Glutamine synthetase.

– Adding acetyl-CoA to glucosamine-1-phosphate produces N-acetylglucosamine (NAG/GlcNAc)

– Finally, add UTP (uridine triphosphate) to N-acetylglucosamine produces

UDP-NAG (UDP-GlcNAc).

– 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:

https://www.youtube.com/watch?v=5YeGje_LK7Q

 

Rerence

Pinho, M. G. Kjos, M. and Weening, J. Nat. Rev. Microbiol. (2013) 11: p. 601-614.

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