Lantibiotics are a class of poly

cyclic peptide Cyclic peptides are polypeptide chains which contain a circular sequence of bonds. This can be through a connection between the amino and carboxyl ends of the peptide, for example in cyclosporin; a connection between the amino end and a side chai ...

antibiotic 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 prevention of ...

s that contain the characteristic thioether

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 ...

lanthionine or methyllanthionine, as well as the unsaturated amino acids dehydroalanine, and

2-aminoisobutyric acid 2-Aminoisobutyric acid (also known as α-aminoisobutyric acid, AIB, α-methylalanine, or 2-methylalanine) is the non-proteinogenic amino acid with the structural formula H2N-C(CH3)2-COOH. It is rare in nature, having been only found in meteorites, ...

. They belong to ribosomally synthesized and post-translationally modified peptides. Lanthionine is composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether (monosulfide) linkage. Lantibiotics are produced by a large number of

Gram-positive bacteria 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 ...

such as '' Streptococcus'' and ''

Streptomyces ''Streptomyces'' is the largest genus of Actinomycetota and the type genus of the family Streptomycetaceae. Over 500 species of ''Streptomyces'' bacteria have been described. As with the other Actinomycetota, streptomycetes are gram-positive, ...

'' to attack other Gram-positive bacteria, and as such, they are considered a member of the bacteriocins. Bacteriocins are classified according to their extent of posttranslational modification. The lantibiotics are a class of more extensively modified bacteriocins, also called Class I bacteriocins. (Bacteriocins for which disulfide bonds are the only modification to the peptide are

Class II bacteriocin Class II bacteriocins are a class of small peptides that inhibit the growth of various bacteria. Many Gram-positive bacteria produce ribosomally synthesized antimicrobial peptides, termed bacteriocins. Bacteriocins for which disulfide bonds a ...

s.) Lantibiotics are well studied because of the commercial use of these bacteria in the food industry for making dairy products such as

cheese Cheese is a dairy product produced in wide ranges of flavors, textures, and forms by coagulation of the milk protein casein. It comprises proteins and fat from milk, usually the milk of cows, buffalo, goats, or sheep. During production, ...

. Nisin and epidermin are members of a family of lantibiotics that bind to

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

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 mech ...

precursor lipid component of target bacteria and disrupt cell wall production. The duramycin family of lantibiotics binds

phosphoethanolamine Phosphorylethanolamine or phosphoethanolamine is an ethanolamine derivative that is used to construct two different categories of phospholipids. One category termed a glycerophospholipid and the other a sphingomyelin, or more specifically within th ...

in the

membranes A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. Bi ...

of its target cells and seem to disrupt several physiological functions.

History

The name lantibiotics was introduced in 1988 as an abbreviation for "lanthionine-containing peptide antibiotics". The first structures of these antimicrobial agents were produced by pioneering work by Gross and Morell in the late 1960s and early 1970s, thus marking the formal introduction of lantibiotics. Since then, lantibiotics such as nisin have been used auspiciously for food preservation and have yet to encounter significant

bacterial resistance Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. P ...

. These attributes of lantibiotics have led to more detailed research into their structures and biosynthetic pathways.

Classification

*Type A lantibiotics are long flexible molecules - e.g., nisin,

bisin Bisin is a naturally occurring lantibiotic (an antibacterial peptide) discovered by University of Minnesota microbiologist Dan O'Sullivan. Unlike earlier lantibiotics discovered, such as nisin, bisin also kills Gram-negative bacteria, including '' ...

subtilisin Subtilisin is a protease (a protein-digesting enzyme) initially obtained from ''Bacillus subtilis''. Subtilisins belong to subtilases, a group of serine proteases that – like all serine proteases – initiate the nucleophilic attack on the p ...

, epidermin, gallidermin Subgroup AI includes

mutacin Mutacin 1140 is a bacteriocin produced by ''Streptococcus mutans''. It has activity against a broad spectrum of Gram-positive bacteria. It is a member of the class of compounds known as lantibiotics. Mutacin 1140 belongs to the epidermin subset ...

II; subgroup AII includes mutacin I and III. *Type B lantibiotics are globular - e.g., mersacidin. actagardine, duramycin, and

cinnamycin Cinnamycin is a tetracyclic antibacterial peptide produced by '' Streptomyces cinnamoneus'' containing 19 amino acid residues including the unusual amino acids ''threo''-3-methyl-lanthionine, ''meso''-lanthionine, lysinoalanine, and 3-hydroxyas ...

. Some contain 2 peptides, e.g. haloduracin.

Examples

(Sublancin may be an S-linked glycopeptide).

Biosynthesis

They are synthesised with a leader polypeptide sequence that is removed only during the transport of the molecule out of the synthesising cell. They are synthesized by

ribosome Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...

s, which distinguishes them from most natural antibiotics. There are four known enzymes (lanthipeptide synthetases) responsible for producing lanthionine rings.

Mechanism of action

Lantibiotics show substantial specificity for some components (e.g.,

) of bacterial

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

especially of Gram-positive bacteria. Type A lantibiotics kill rapidly by pore formation, type B lantibiotics inhibit peptidoglycan biosynthesis. They are active in very low concentrations.

Application

Food preservation

Lantibiotics are produced by Gram-positive bacteria and show strong antimicrobial action toward a wide range of other Gram-positive bacteria. As such, they have become attractive candidates for use in

food preservation Food preservation includes processes that make food more resistant to microorganism growth and slow the oxidation of fats. This slows down the decomposition and rancidification process. Food preservation may also include processes that inhibit ...

(by inhibiting pathogens that cause food spoilage) and the pharmaceutical industry (to prevent or fight infections in humans or animals).

Clinical antibiotic

One type known as B lantibiotic NVB302 entered phase 1 clinical trials in 2011 for use against ''

Clostridium difficile ''Clostridioides difficile'' (syn. ''Clostridium difficile'') is a bacterium that is well known for causing serious diarrheal infections, and may also cause colon cancer. Also known as ''C. difficile'', or ''C. diff'' (), is Gram-positive spec ...

'', and reported good results in 2012.

Databases

BACTIBASE is an open-access database for bacteriocins including lantibiotics. LANTIBASE is a lantibiotic specific resource.

References

External links

Lantibase
a database of lantibiotics * {{cite web , url = http://bactibase.hammamilab.org/bacteriocinslist.php?Class=lantibiotic , title = Complete list of lantibiotics , work = BACTIBASE Database Peripheral membrane proteins