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 that surrounds some Cell type, cell types, found immediately outside the cell membrane. It can be tough, flexible, and sometimes rigid. Primarily, it provides the cell with structural support, shape, protection, ...

component of some

Archaea Archaea ( ) is a Domain (biology), domain of organisms. Traditionally, Archaea only included its Prokaryote, prokaryotic members, but this has since been found to be paraphyletic, as eukaryotes are known to have evolved from archaea. Even thou ...

that differs from

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

peptidoglycan Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like layer (sacculus) that surrounds the bacterial cytoplasmic membrane. The sugar component consists of alternating ...

in chemical structure, but resembles bacterial peptidoglycan in function and physical structure. Pseudopeptidoglycan, in general, is only present in a few methanogenic archaea. The basic components are ''N''-acetylglucosamine and ''N''-acetyltalosaminuronic acid (bacterial peptidoglycan containing ''N''-acetylmuramic acid instead), which are linked by β-1,3-glycosidic bonds.

Lysozyme Lysozyme (, 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 hydrolase ...

, 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 Common descent is a concept in evolutionary biology applicable when one species is the ancestor of two or more species later in time. According to modern evolutionary biology, all living beings could be descendants of a unique ancestor commonl ...

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 comm ...

, but recent structural 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 (biology), cell. Integration of prophages into the bacte ...

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 over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

, 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. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

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 The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

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

ortholog Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speci ...

ous-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 Phosphoglucomutase () is an enzyme that transfers a phosphate group on an α-D-glucose monomer from the 1 to the 6 position in the forward direction or the 6 to the 1 position in the reverse direction. More precisely, it facilitates the interconv ...

(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 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''-acetyl--glucosamine (a 2-amino-2-deoxysugar) ...

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 beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...

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 pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

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 many are 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, pseudopeptidoglycan 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 and Methanopyrales. Some genera under these orders are: * '' Methanobacterium'' * '' Methanobrevibacter'' * '' Methanothermobacter'' * '' Methanothermus'' * '' Methanosphaera'' * ''

Methanopyrus ''Methanopyrus'' is a genus of methanogen, with a single described species, ''Methanopyrus kandleri''. It is a rod-shaped hyperthermophile, discovered on the wall of a black smoker from the Gulf of California at a depth of 2,000 m, at temper ...