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 A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mec ...

component of some

Archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaeba ...

that differs from

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

peptidoglycan Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ba ...

in chemical structure, but resembles bacterial peptidoglycan in function and physical structure. Pseudopeptidoglycan, in general, is only present in a few

methanogenic archaea Methanogens are microorganisms that produce methane as a metabolic byproduct in hypoxic conditions. They are prokaryotic and belong to the domain Archaea. All known methanogens are members of the archaeal phylum Euryarchaeota. Methanogens are co ...

. The basic components are

N-acetylglucosamine ''N''-Acetylglucosamine (GlcNAc) is an amide derivative of the monosaccharide glucose. It is a secondary amide between glucosamine and acetic acid. It is significant in several biological systems. It is part of a biopolymer in the bacter ...

and N-acetyltalosaminuronic acid (bacterial peptidoglycan containing ''N''-acetylmuramic acid instead), which are linked by β-1,3-glycosidic bonds.

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 ...

, a host defense mechanism present in human secretions (e.g. saliva and tears) breaks β-1,4-glycosidic bonds to degrade peptidoglycan. However, because pseudopeptidoglycan has β-1,3-glycosidic bonds, lysozyme is ineffective. It was thought from these large differences in cell wall chemistry that archaeal cell walls and bacterial cell walls have not evolved from a common ancestor but are only the result of a

convergent evolution Convergent evolution is the independent evolution of similar features in species of different periods or epochs in time. Convergent evolution creates analogous structures that have similar form or function but were not present in the last com ...

, but recent structual work has revealed deeper homology. No archaeal enzymes are known that cleave the β-1,3-glycosidic bonds in pseudopeptidoglycan, but it can be degraded by pseudomurein endoisopeptidase encoded by two

prophage A prophage is a bacteriophage (often shortened to "phage") genome that is integrated into the circular bacterial chromosome or exists as an extrachromosomal plasmid within the bacterial cell. Integration of prophages into the bacterial host is th ...

s. The pseudomurein endoisopeptidases function by cleaving the peptide links between adjacent pseudopeptidoglycan strands.

Structure

Pseudopeptidoglycan is composed of two sugars, N-acetylglucosamine and N-acetyltalosaminuronic acid. These sugars are made of different

amino acids 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 am ...

, and the peptide cross-links within pseudopeptidoglycan are formed with different amino acids. The

peptide bond In organic chemistry, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 (nitrogen number two) of another, along a peptide or protein cha ...

is formed between the

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated − ...

of a N-acetyltalosaminuronic acid and a

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 ...

of a parallel N-acetyltalosaminuronic acid. Pseudopeptidoglycan, like peptidoglycan in bacteria, forms a mesh-like layer outside of the plasma membrane of the archaea.

Function

Only a few methanogenic archaea have cell walls composed of pseudopeptidoglycan. This component functions much like peptidoglycan in a bacterial cell. Pseudopeptidoglycan is used by the archaeal cell to determine its shape and provide structure to the cell. It is also used to protect the cell from undesired molecules or anything harmful in its environment.

Biosynthesis

PPG is produced by enzymes of two gene clusters. Recent work on the peptide ligases show, surprisingly, a common origin with murein synthesis. The pathway is now known to include the orthologous-to-bacteria CarB, MurC/D (peptide ligase), MurG, MraY, UppP, UppS, and flippase presumably performing an analogous function, and two novel but conserved transmembrane proteins. GlmM and GlmU, which produce UDP-GlcNAc in bacteria, are also present with phosphoglucomutase (PGM). Half of the species also have MurT and GatD, known to perform cell wall modifications in bacteria. No orthologous cross-linking enzymes have been identified. Notably, "formation of the disaccharide moiety of the glycopeptide monomer occurs before the transfer to membrane protein by MraY", as opposed to after in bacteria. Further work would be needed to connect these information into a coherent pathway.

Effects of different bacterial medicines on pseudopeptidoglycan

Lysozyme

Lysozyme is a natural defense mechanism in humans that has the ability to break down peptidoglycan in bacterial cells. It degrades the peptidoglycan by targeting the β-1,4-glycosidic bonds that connect the alternating

amino sugars In organic chemistry, an amino sugar (or more technically a 2-amino-2-deoxysugar) is a sugar molecule in which a hydroxyl group has been replaced with an amine group. More than 60 amino sugars are known, with one of the most abundant being ''N'' ...

in which it is composed of. This degradation of the glycosidic bonds within peptidoglycan cause the sugars to separate and inhibit the structural integrity of the peptidoglycan and the bacteria. Pseudopeptidoglycan, however, is composed of a different acidic amino sugar, which is N-acetyltalosaminuronic acid. This difference is the reason that it has β-1,3-glycosidic bonds (as opposed to the β-1,4-glycosidic bonds in bacteria). Lysozymes targets the linkage in peptidoglycan, and without that, becomes ineffective against pseudopeptidoglycan.

Penicillin

Penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from '' Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum usin ...

is a group of

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and preventio ...

that have been effective against many

bacterial infections Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and are often beneficial but others can cause infectious diseases. The number of t ...

. It attacks bacteria by targeting and inhibiting the transpeptidase that catalyzes the cross-linking of the amino sugars in peptidoglycan. However, peptidoglycan contains different amino sugars, and therefore, a different catalysis enzyme is used. The different amino acids cause antibiotics, that target cell walls like penicillin, to be ineffective against pseudopeptidoglycan.

Taxonomic distribution

PPG is found in the archaeal orders of

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 composition ...

and Methanopyrales. Some genera under these orders are: * Methanobacterium *

Methanobrevibacter In taxonomy, ''Methanobrevibacter'' is a genus of the Methanobacteriaceae.See the NCBIbr>webpage on Methanobrevibacter Data extracted from the The species within ''Methanobrevibacter'' are strictly anaerobic archaea that produce methane, for t ...

Methanothermobacter In taxonomy, ''Methanothermobacter'' is a genus of the Methanobacteriaceae.See the NCBIbr>webpage on Methanothermobacter Data extracted from the The species within this genus are thermophilic and grow best at temperatures between 55°C and ...

Methanothermus In taxonomy, ''Methanothermus'' is a genus of microbes within Methanothermaceae. The species within this genes are hyperthermophiles and strictly anaerobic. They produce energy through the reduction of carbon dioxide with hydrogen to produce me ...

Methanosphaera In taxonomy, ''Methanosphaera'' is a genus of microbes within the family Methanobacteriaceae.See the NCBIbr>webpage on Methanosphaera Data extracted from the It was distinguished from other genera within Methanobacteriaceae in 1985 on the basi ...

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 ...