Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

s that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...

( domain ''Bacteria''). The sugar component consists of alternating residues of β-(1,4) linked ''N''-acetylglucosamine (NAG) and ''N''-acetylmuramic acid (NAM). Attached to the ''N''-acetylmuramic acid is a

oligopeptide An oligopeptide, often just called peptide ('' oligo-'', "a few"), consists of two to twenty amino acids and can include dipeptides, tripeptides, tetrapeptides, and pentapeptides. Some of the major classes of naturally occurring oligopeptides in ...

chain made of three to five amino acids. The peptide chain can be cross-linked to the peptide chain of another strand forming the 3D mesh-like layer. Peptidoglycan serves a structural role in the bacterial cell wall, giving structural strength, as well as counteracting the osmotic pressure of the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

. This repetitive linking results in a dense peptidoglycan layer which is critical for maintaining cell form and withstanding high osmotic pressures, and it is regularly replaced by peptidoglycan production. Peptidoglycan hydrolysis and synthesis are two processes that must occur in order for cells to grow and multiply, a technique carried out in three stages: clipping of current material, insertion of new material, and re-crosslinking of existing material to new material. The peptidoglycan layer is substantially thicker in

Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

(20 to 80 nanometers) than in

Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...

bacteria (7 to 8 nanometers). Depending on pH growth conditions, the peptidoglycan forms around 40 to 90% of the cell wall's

dry weight Vehicle weight is a measurement of wheeled motor vehicles; either an actual measured weight of the vehicle under defined conditions or a gross weight rating for its weight carrying capacity. Curb or kerb weight Curb weight (U.S. English) or kerb ...

of Gram-positive bacteria but only around 10% of Gram-negative strains. Thus, presence of high levels of peptidoglycan is the primary determinant of the characterisation of bacteria as

. In Gram-positive strains, it is important in attachment roles and

serotyping A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their surface antigens, allowing the epi ...

purposes. For both Gram-positive and Gram-negative bacteria, particles of approximately 2 nm can pass through the peptidoglycan. It is difficult to tell whether an organism is gram-positive or gram-negative using a microscope; Gram staining, created by

Hans Christian Gram Hans Christian Joachim Gram (13 September 1853 – 14 November 1938) was a Danish bacteriologist noted for his development of the Gram stain, still a standard technique to classify bacteria and make them more visible under a microscope. Early l ...

in 1884, is required. The bacteria are stained with several dyes such as crystal violet, iodine alcohol, and safranin using the gram staining procedure. Gram positive cells are purple after staining, while Gram negative cells are red.

Structure and importance

The peptidoglycan layer in the bacterial cell wall is a crystal lattice structure formed from linear chains of two alternating amino sugars, namely ''N''-acetylglucosamine (GlcNAc or NAGA) and ''N''-acetylmuramic acid (MurNAc or NAMA). The alternating sugars are connected by a β-(1,4)-

glycosidic bond A glycosidic bond or glycosidic linkage is a type of covalent bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate. A glycosidic bond is formed between the hemiacetal or hemiketal group ...

. Each MurNAc is attached to a short (4- to 5-residue)

chain, containing L-alanine, D-glutamic acid, ''meso''-diaminopimelic acid, and D-alanine in the case of ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

'' (a Gram-negative bacterium) or L-alanine, D-glutamine, L-lysine, and D-alanine with a 5-

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...

interbridge between tetrapeptides in the case of '' Staphylococcus aureus'' (a Gram-positive bacterium). Peptidoglycan is one of the most important sources of

D-amino acid D-Amino acids are amino acids where the stereogenic carbon alpha to the amino group has the D-configuration. For most naturally-occurring amino acids, this carbon has the L-configuration. D-Amino acids are occasionally found in nature as residue ...

s in nature. By enclosing the inner membrane, the peptididoglycan layer protects the cell from lysis caused by the

turgor Turgor pressure is the force within the cell that pushes the plasma membrane against the cell wall. It is also called ''hydrostatic pressure'', and is defined as the pressure in a fluid measured at a certain point within itself when at equilibri ...

pressure of the cell. When the cell wall grows, it retains its shape throughout its life, so a rod shape will remain a rod shape, and a spherical shape will remain a spherical shape for life. This happens because the freshly added septal material of synthesis transforms into a hemispherical wall for the offspring cells.

Cross-link In chemistry and biology a cross-link is a bond or a short sequence of bonds that links one polymer chain to another. These links may take the form of covalent bonds or ionic bonds and the polymers can be either synthetic polymers or natural ...

ing between

s in different linear amino sugar chains occurs with the help of the enzyme DD-transpeptidase and results in a 3-dimensional structure that is strong and rigid. The specific amino acid sequence and molecular structure vary with the bacterial

species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...

. The different peptidoglycan types of bacterial cell walls and their taxonomic implications have been described. Archaea ( domain ''Archaea'') do not contain peptidoglycan (murein). Some Archaea contain

pseudopeptidoglycan Pseudopeptidoglycan (also known as pseudomurein;White, David. (1995) ''The Physiology and Biochemistry of Prokaryotes'', pages 6, 12-21. (Oxford: Oxford University Press). . PPG hereafter) is a major cell wall component of some Archaea that differs ...

(pseudomurein, see below). File:Mureine.svg, The structure of peptidoglycan. NAG = ''N''-acetylglucosamine (also called GlcNAc or NAGA), NAM = ''N''-acetylmuramic acid (also called MurNAc or NAMA). File:Gram-positive cellwall-schematic.png,

cell wall File:PBP catalysis.svg,

Penicillin binding protein Penicillin-binding proteins (PBPs) are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was discove ...

forming cross-links in newly formed bacterial cell wall. Peptidoglycan is involved in

binary fission Binary may refer to: Science and technology Mathematics * Binary number, a representation of numbers using only two digits (0 and 1) * Binary function, a function that takes two arguments * Binary operation, a mathematical operation that ta ...

during bacterial cell reproduction.

L-form bacteria L-form bacteria, also known as L-phase bacteria, L-phase variants or cell wall-deficient (CWD) bacteria, are growth forms derived from different bacteria. They lack cell walls. Peptidoglycan ( murein) is absent. Two types of L-forms are distingui ...

and mycoplasmas, both lacking peptidoglycan cell walls, do not proliferate by binary fission, but by a budding mechanism. In the course of early evolution, the successive development of boundaries (membranes, walls) protecting first structures of life against their environment must have been essential for the formation of the first cells (cellularisation). The invention of rigid peptidoglycan (murein) cell walls in bacteria (domain ''Bacteria'') was probably the prerequisite for their survival, extensive radiation and colonisation of virtually all habitats of the geosphere and hydrosphere.

Biosynthesis

The peptidoglycan monomers are synthesized in the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

and are then attached to a membrane carrier bactoprenol. Bactoprenol transports peptidoglycan monomers across the cell membrane where they are inserted into the existing peptidoglycan. # In the first step of peptidoglycan synthesis,

glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral ...

, which is an amino acid, donates an amino group to a sugar,

fructose 6-phosphate Fructose 6-phosphate (sometimes called the Neuberg ester) is a derivative of fructose, which has been phosphorylated at the 6-hydroxy group. It is one of several possible fructosephosphates. The β-D-form of this compound is very common in cells. ...

. This reaction, catalyzed by EC 2.6.1.16 (GlmS), turns fructose 6-phosphate into glucosamine-6-phosphate. # In step two, an acetyl group is transferred from

acetyl CoA Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...

to the amino group on the glucosamine-6-phosphate creating ''N''-acetyl-glucosamine-6-phosphate. This reaction is EC 5.4.2.10, catalyzed by GlmM. # In step three of the synthesis process, the ''N''-acetyl-glucosamine-6-phosphate is isomerized, which will change ''N''-acetyl-glucosamine-6-phosphate to ''N''-acetyl-glucosamine-1-phosphate. This is EC 2.3.1.157, catalyzed by GlmU. # In step 4, the ''N''-acetyl-glucosamine-1-phosphate, which is now a monophosphate, attacks UTP. Uridine triphosphate, which is a pyrimidine

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecule ...

, has the 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 (2,4). (When UDP is used as an energy source, it gives off an inorganic phosphate.) This initial stage, is used to create the precursor for the NAG in peptidoglycan. This is EC 2.7.7.23, also catalyzed by GlmU, which is a bifunctional enzyme. # In step 5, some of the UDP-N-acetylglucosamine (UDP-GlcNAc) is converted to UDP-MurNAc (UDP-N-acetylmuramic acid) by the addition of a lactyl group to the glucosamine. Also in this reaction, the C3 hydroxyl group will remove a phosphate from the alpha carbon of

phosphoenolpyruvate Phosphoenolpyruvate (2-phosphoenolpyruvate, PEP) is the ester derived from the enol of pyruvate and phosphate. It exists as an anion. PEP is an important intermediate in biochemistry. It has the highest-energy phosphate bond found (−61.9 kJ/m ...

. This creates what is called an enol derivative. EC 2.5.1.7, catalyzed by MurA. # In step 6, the enol is reduced to a “lactyl moiety” by NADPH in step six. EC 1.3.1.98, catalyzed by MurB. # In step 7, the UDP–MurNAc is converted to UDP-MurNAc pentapeptide by the addition of five amino acids, usually including the dipeptide D-alanyl-D-alanine. This is a string of three reactions: EC 6.3.2.8 by MurC, EC 6.3.2.9 by MurD, and EC 6.3.2.13 by MurE. Each of these reactions requires the energy source ATP. This is all referred to as Stage one. Stage two occurs in the cytoplasmic membrane. It is in the membrane where a lipid carrier called bactoprenol carries peptidoglycan precursors through the cell membrane. # Undecaprenyl phosphate will attack the UDP-MurNAc penta, creating a PP-MurNac penta, which is now a lipid ( lipid I). EC 2.7.8.13 by MraY. # UDP-GlcNAc is then transported to MurNAc, creating Lipid-PP-MurNAc penta-GlcNAc (

lipid II Lipid II is a precursor molecule in the synthesis of the cell wall of bacteria. It is a peptidoglycan, which is amphipathic and named for its bactoprenol hydrocarbon chain, which acts as a lipid anchor, embedding itself in the bacterial cell me ...

), a disaccharide, also a precursor to peptidoglycan. EC 2.4.1.227 by MurG. # Lipid II is transported across the membrane by

flippase Flippases (rarely spelled flipases) are transmembrane lipid transporter proteins located in the membrane which belong to ABC transporter or P4-type ATPase families. They are responsible for aiding the movement of phospholipid molecules between th ...

(MurJ), a discovery made in 2014 after decades of searching. Once it is there, it is added to the growing glycan chain by the enzyme peptidoglycan glycosyltransferase (GTase, EC 2.4.1.129). This reaction is known as tranglycosylation. In the reaction, the hydroxyl group of the GlcNAc will attach to the MurNAc in the glycan, which will displace the lipid-PP from the glycan chain. # In a final step, the DD-transpeptidase (TPase, EC 3.4.16.4) crosslins individual glycan chains. This protein is also known as the

penicillin-binding protein Penicillin-binding proteins (PBPs) are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was discov ...

. Some versions of the enzyme also performs the glycosyltransferase function, while others leave the job to a separate enzyme.

Inhibition

Some antibacterial drugs such as penicillin interfere with the production of peptidoglycan by binding to bacterial enzymes known as

penicillin-binding proteins Penicillin-binding proteins (PBPs) are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was discove ...

or DD-transpeptidases. Penicillin-binding proteins form the bonds between oligopeptide crosslinks in peptidoglycan. For a bacterial cell to reproduce through

, more than a million peptidoglycan subunits (NAM-NAG+oligopeptide) must be attached to existing subunits. Mutations in genes coding for transpeptidases that lead to reduced interactions with an antibiotic are a significant source of emerging antibiotic resistance. Since peptidoglycan is also lacking in L-form bacteria and in mycoplasmas, both are resistant against penicillin. Other steps of peptidoglycan synthesis can also be targeted. The topical antibiotic bacitracin targets the utilization of C55-isoprenyl pyrophosphate.

Lantibiotics Lantibiotics are a class of polycyclic peptide antibiotics that contain the characteristic thioether amino acids lanthionine or methyllanthionine, as well as the Saturated and unsaturated compounds, unsaturated amino acids dehydroalanine, and 2-Am ...

, which includes the food preservative

nisin Nisin is a polycyclic antibacterial peptide produced by the bacterium ''Lactococcus lactis'' that is used as a food preservative. It has 34 amino acid residues, including the uncommon amino acids lanthionine (Lan), methyllanthionine (MeLan), di ...

, attack lipid II.

Lysozyme Lysozyme (EC 3.2.1.17, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside ...

, 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 bonds in peptidoglycan (see above).

Pseudopeptidoglycan (Pseudomurein)

In some archaea, i.e. members of the

Methanobacteriales In taxonomy, the Methanobacteriales are an order of the Methanobacteria. Species within this order differ from other methanogens in that they can use fewer catabolic substrates and have distinct morphological characteristics, lipid compositi ...

and in the genus

Methanopyrus In taxonomy, ''Methanopyrus'' is a genus of the Methanopyraceae. ''Methanopyrus'' is a genus of methanogen, with a single described species, ''M. kandleri''. It is a rod-shaped hyperthermophile, discovered on the wall of a black smoker from the ...

(pseudomurein) has been found. In pseudopeptidoglycan the sugar residues are β-(1,3) linked ''N''-acetylglucosamine and ''N''-acetyltalosaminuronic acid. This makes the cell walls of such archaea insensitive to

lysozyme Lysozyme (EC 3.2.1.17, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside ...

. The biosynthesis of pseudopeptidoglycan has been described.

References

External links