Peptidoglycan is a polymer that forms the cell wall of bacteria and provides structural strength. It consists of alternating sugars (N-acetylglucosamine and N-acetylmuramic acid) linked together into a mesh-like layer with cross-linking peptide chains. Peptidoglycan is synthesized through a two-stage process where sugar nucleotides and amino acids are assembled into a lipid carrier on the inner membrane before being polymerized into the cell wall. Several antibiotics are able to inhibit peptidoglycan synthesis by binding to enzymes involved in cross-linking, preventing cell wall assembly and causing bacterial cell death.

1. PEPTIDOGLYCAN
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2. CONTENTS
 INTRODUCTION
 STRUCTURE
 BIOSYTHESIS OF PEPTIDOGLYCAN
 INHIBITON
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3. Peptidoglycan
INTRODUCTION
 Peptido means short peptide chain and glycan means polysaccharide.
 Polysaccharide contain short peptide chain.
 Peptidoglycan is a heteropolymer or heteropolysaccharides due to present of the sugar in it i.e
 N-acetyl muramic acid (NAMA)
β (1,4) Glycosidic linkage
 N-acetyl glucosamine (NAGA)
 Peptide cross bridges are linked to NAMA which is very unique to bacteria.
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4.  Peptidoglycan is a heteropolymer consists of sugar
and amino acids that forms mesh like layer outside
the plasma membrane of most of the bacteria forming
cell wall.
 It is also known as the ‘’MUREIN ‘’.
 Peptidoglycan involve in Binary fission for Bacterial reproduction.
 Peptidoglycan confers strength to the cell wall, rigidity, shape and osmotic
pressure against any defect.
 Peptidoglycan forms around 90% of the dry weight of gram positive bacteria
only 10% of gram negative bacteria.
 The Peptidoglycan layer is substantially thicker in gram positive bacteria than
in gram negative bacteria.
 Outer membrane is absent in gram positive bacteria present in gram negative
bacteria.
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5. Structure of peptidoglycan
 The peptidoglycan layer in the bacterial wall is a crystal lattice
structure and is made of glycan strands of alternating residues of
N-acetylglucosamine and N-acetylmuramic acid linked by 1,4
glycosidic bonds between C1 and C4 respectively.
 N-acetylmuramic acid is a modified form of N-acetylglucosamine in
which a lactyl group has been attached to the c3 carbon and attached
to each NAMA is a tetrapeptide.
 Tetrapeptide is a L-alanyl, D-glutamyl, L-lysine, D-alanine .
 The amino acid in position 3 varies with the species of bacterium.
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7.  The tetrapeptide chains are cross-linked by peptide bonds . There is a great deal of
variability in the composition of the cross-links among the different groups of bacteria.
 In fact, amino acid composition and cross-link location have been used for taxonomic
purpose.
 In some bacteria the cross-linking is direct for example
 Between D-alanine and diaminopimelic acid in gram-negative bacteria and many Bacillus
species.
 There are three L-alanine and one L-threonine in Micrococcus roseus.
 And three glycines and two L-serines in Staphylococcus epidermidis.
 Cross-linking between amino acids in different linear sugar chains occurs with the help of the
enzyme DD-Transpeptidase and results in 3-dimensional structure that is strong and rigid.
 The specific amino acids sequence and molecular structure vary with the bacterial species.
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8. BIOSYTHESIS OF PEPTIDOGLYCAN
 The Biosynthesis of Bacteria cell wall peptidoglycan is a complex process that involve
enzymes reactions that take place in the cytoplasm and on the inner side and outer
side of the cytoplasmic membrane.
 The Biosynthesis of Bacterial peptidoglycan is a complex two stage process.
 First stage :- Formation of the disaccharides peptide monomer unit
 Second stage :- polymerization reactions accompanied by interactions of the newly
made peptidoglycan material into cell wall. The assembly of the peptidoglycan unit
proceeds by a series of cytoplasmic membrane reactions.
 The stages can be written in four stages also.
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9.  First stage:- take place in cytosol.
The two amino sugars that are precursors to the peptidoglycan are N-acetylglucosamine and N-
acetylmuramic acid . Both amino sugars are made from fructose-6-phosphate.
 Step(1):- glutamine, which is aa amino acid ,denotes am amino group to a sugar . This turns fructose-6-
phosphate to glucosamine-6-phosphate in the presence of enzyme called glucosamine-6-phosphate
synthase [ Glm S]
fructose-6-phosphate Glm S glucosamine-6-phosphate
 Step(2):-In this step isomerisation takes place, that glucosamine-6-phosphate to glucosamine-1-
phosphate in the presence of phosphoglucosamine mutase [ Glm M].
glucosamine-6-phosphate Glm M glucosamine-1-phosphate
 Step(3):-An acetyl group is transferred from acetyl CoA to the amino group on the glucosamine-1-
phosphate creating N-acetyl glucosamine-1-phosphate, in presence of enzyme glucosamine-1-
phosphate acetyltransferase [ Glm U].
glucosamine-1-phosphate Glm U N-acetyl glucosamine-1-phosphate
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10.  Step(4):-The N-acetyl-glucosamine-1-phosphate which is now a monophosphate,
attacks UTP (Uridine triphosphate) , which is a pyrimidine nucleotide , it has
ability to act as an energy source.
In this particular reaction, after the monophosphate has attacked the UTP, an
inorganic pyrophosphate is given off and is replaced by the monophosphate, creating
UDP-N-acetylglucosamine (UDP-Glc NAC) . This initial stage, is used to create the
precursor for the NAG in peptidoglycan. The enzyme is N-acetylglucosamine-1-
phosphate uridyltransferase.
N-acetyl-glucosamine-1-P UTP UDP UDP-Glc NAC
Glm U
UDP-Glc NAC is also present in eukaryotes because Glc NAC is an important buildings
block for major biomolecules such as chitin and glycoproteins . However, as the
eukaryotic pathway of UDP-Glc NAC biosynthesis is different from the prokaryotic
pathway, the latter can be a target for specific antibacterial compounds.
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11.  Step(5):- In this step UDP-Glc NAc is converted into UDP-N-acetylglucosamine-enol-
pyruvate (UDP-Glc NAc -enol-pyruvate) by the addition of lactyl group to the
glucosamine . Also in this reaction the c3 hydroxyl group will remove a inorganic
phosphate(Pi) from the alpha carbon of phosphoenol pyruvate. In the presence of
the enzyme is MurA ( formerly known as MurZ) , the MurA reaction pathway follows
an addition-elimination mechanism.
UDP-Glc NAc PEP UDP-Glc NAc -enol-pyruvate
MurA or MurZ
 Step(6):- In this they undergo a reduction catalysed by MurB using one equivalent of
NADPH and a solvent-derived proton. This two-electron reduction creates the lactyl
ether of UDP-N-acetylmuramic acid (UDP-Mur NAc).
 UDP-Glc NAc -enol-pyruvate NADPH UDP-Mur NAc
MurB
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12.  Step(7):-In this stepwise assembly of the peptide stem of peptidoglycan is
ensured by a series of four essential enzymes, known as the Mur ligases
(MurC, D, E and F) . These provide for additions of L-alanine (MurC), D-glutamic
acid (MurD), L-lysine (MurE) and D-alanine-D-alanine (MurF) in case of
Escherichia coli .
UDP-Mur NAc MurC UDP-Mur NAc-L-Ala
The Mur ligases catalyse the formation of an amide or a peptide bond with
simultaneous forming of ADP and Pi from ATP. A divalent cation Mg2+ or Mn2+
is essential for the reaction. The MurC ligase adds the first amino acid of peptide
stem.
 Step(8):- The second amino acid residue of the peptide stem is in most species
D-glutamic acid .
UDP-Mur NAc-L-Ala MurD UDP-Mur NAc-dipeptide
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13.  Step(9):- The third amino acid of the peptide stem is L-lysine is added.
UDP-Mur NAc-dipeptide MurE UDP-Mur NAc-Tripeptide
 Step(10):- The fourth amino acid of the peptide stem is D-alanine-D-alanine
added.
UDP-Mur NAc- Tripeptide MurF UDP-Mur NAc-pentapeptide
 Second phase:- takes place in cytoplasmic membrane (cell membrane).
 Then UDP-Mur NAc-pentapeptide attached to a lipid carrier called Bactoprenol
or undecaprenyl, is a C55 isoprenoid phosphate. They are joined by a
pyrophosphate bond .
UDP-NAM-pentapeptide undecaprenyl bactoprenol -pp-NAM-
MurY pentapeptide ( Lipid I )
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14.  UDP transfers NAG to the bactoprenol-pp-NAM-pentapeptide, generating Lipid II.
If a pentaglycine interbridge is required, it is created using special glycl-Trna
molecules but not ribosomes. Interbridge formation occurs at the cytoplasmic side
of the membrane. In the presence of enzyme MurG.
bactoprenol-pp-NAM- MurG bactoprenol-pp-NAM-NAG
pentapeptide pentapeptide
I. (Lipid II)
 Lipid 11 is flipped across the membrane by the flippase enzyme, but this molecule
is transported through the membrane is still not understood. The NAM-NAG-
Pentapeptide is attached to the growing end of a nascent peptidoglycan chain
that is held at the membrane by a bactoprenol molecule. Then these bactoprenol
donor moves back across the membrane, it loses one phosphate , becoming
bactoprenol phosphate. It is now ready to begin a new cycle.
Lipid II Peptidoglycan
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15. Fructose-6-P UDP-Mur Nac bactoprenol-pp-NAM-
GlmS Gln MurC L-Ala pentapeptide
(Lipid I)
Glucosamine-6-P UDP-Mur NAc-L-Ala MurG UDP-Glc NAc
GlmM MurD D-Glu
Glucosamine-1-P UDP-Mur NAc-dipeptide bactoprenol-pp-NAM-NAG
GlmU acetyl CoA MurE L-Lys Pentapeptide (Lipid II)
N-acetylglucosime-1-P UDP-Mur NAc-tripeptide
GlmU UTP MurF D-Ala-D-Ala
UDP-GlcNac UDP-Mur NAc-pentapeptide Peptidoglycan
MurA PEP
MurY undecaprenyl-p
UDP-GlcNAc-enolpyurvate
MurB NADPH
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16. INHIBITION
 Some antibacterial drugs such as pencillin interfere with the
production of peptidoglycan by binding to bacterial enzymes known as
pencillin binding proteins or DD-transpeptidase.
 Pencillin-binding proteins form the bonds oligopeptides cross links in
peptidoglycan.
 Lysozyme which is found in tears and constitutes part of the body’s
innate immune system exerts its’ antibacterial effect by breaking the
β(1,4)-glycosidic linkage or bonds in peptidoglycan.
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17. REFERENCE
 Microbial physiology
- Albert Moat
- Michael P. Spector
- John W. Foster
 The Physiology and Biochemistry
of Prokaryotes - David white
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