1. The cell wall peptidoglycan of bacteria is synthesized in three major stages, with stage 3 involving a transpeptidation reaction that cross-links parallel peptidoglycan chains and is inhibited by penicillin. 2. By repetitive additions of disaccharide units with pentapeptide side chains and cross-linking chains, the bacterial cell becomes surrounded by a single gigantic peptidoglycan molecule. 3. Peptidoglycan synthesis is regulated at multiple levels to ensure shape-maintaining growth and cell division.

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PEPTIDOGLYCAN SYNTHESIS IN
BACTERIA: Pathway (Stage 3) and
Regulation

2. INTRODUCTION
The cell wall peptidoglycan, or murein, of bacteria is synthesized
in three major stages.
 Stage 1, where N-acetylmuramylpentapeptide, a recurring
unit of the backbone structure, is synthesized in the form of
its UDP derivative from its precursors N-Acetylglucosamine,
phosphoenolpyruvate and five amino acid units.
 Stage 2, where N-acetylmuramylpentapeptide is first
transferred enzymatically from UDP to a membrane-bound
lipid intermediate, undecaprenyl phosphate and then added
to a monosaccharide unit to yield the recurring disaccharide
of the peptidoglycan backbone, N-
acetylmuramylpentapeptide-β-(4 1)-N-acetylglucosamine,
attached to the undecaprenyl phosphate. Short cross linking
peptide chains are then added to the disaccharide.

4. Stage 3
 In the last stage (3) of the cell-wall synthesis, the cross
linkage between parallel peptidoglycan chains is
established through a transpeptidation reaction in which
the amino terminal glycine residue of the cross-linking
chain displaces the carboxyl-terminal D-alanine from the
end of the pentapeptide side chain of an N-
acetylmuramylpentapeptide residue in the adjacent
peptidoglycan chain;
 It is this reaction that is inhibited by penicillin.
 Penicillin thus prevents completion of the synthesis of
the cell wall at its last stage, after the bacterial cell has
already made a very heavy biosynthetic investment.

6. By repetitive additions of the
disaccharide units with their
pentapeptide side chains and
cross-linking chains, followed
by cross-linking, the entire
bacterial cell becomes
surrounded by a single,
gigantic saccular molecule of
peptidoglycan.

7. REGULATION
Peptidoglycan synthesis is regulated at multiple levels to
ensure shape-maintaining growth and cell division.
 In some gram-positive bacteria the rigid peptidoglycan
framework of the cell is covered with a layer of teichoic
acid. Sugar side chains are then introduced into the
teichoic acid chain from UDP derivatives.
 In gram-negative organisms, such as E. coli, the
peptidoglycan framework is surrounded by a complex
polymeric lipopolysaccharide.