Lantibiotics
Encyclopedia
Lantibiotics are a class of peptide
antibiotic
s that contain the characteristic polycyclic thioether
amino acids lanthionine
or methyllanthionine, as well as the unsaturated
amino acids dehydroalanine
and 2-aminoisobutyric acid
.
Lantibiotics are produced by a large number of Gram-positive bacteria such as Streptococcus
and Streptomyces
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 bond
s are the only modification to the peptide are Class II bacteriocin
s.)
Lantibiotics are well studied because of the commercial use of these bacteria in the food industry for making dairy products such as cheese
.
Nisin
and epidermin are members of a family of lantibiotics that bind to a cell wall precursor lipid component of target bacteria and disrupt cell wall production. The duramycin family of lantibiotics binds phosphoethanolamine in the membranes
of its target cells and seem to disrupt several physiological functions.
-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. These attributes of lantibiotics have led to more detailed research into their structures and biosynthetic pathways
.
As such they have become attractive candidates for use in food preservation
(by inhibiting pathogens that cause food spoilage) and the pharmaceutical industry (to prevent or fight infections in humans or animals).
One type B lantibiotic NVB302 entered clinical trials in 2011 for use against Clostridium difficile
.
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s that contain the characteristic polycyclic thioether
Thioether
A thioether is a functional group in organosulfur chemistry with the connectivity C-S-C as shown on right. Like many other sulfur-containing compounds, volatile thioethers have foul odors. A thioether is similar to an ether except that it contains a sulfur atom in place of the oxygen...
amino acids lanthionine
Lanthionine
Lanthionine is a nonproteinogenic amino acid with the chemical formula . As the monosulfide analog of cystine, lanthionine is composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage...
or methyllanthionine, as well as the unsaturated
Saturation (chemistry)
In chemistry, saturation has six different meanings, all based on reaching a maximum capacity...
amino acids dehydroalanine
Dehydroalanine
Dehydroalanine is an uncommon amino acid found in peptides of microbial origin ....
and 2-aminoisobutyric acid
2-Aminoisobutyric acid
2-Aminoisobutyric acid, or α-aminoisobutyric acid or α-methylalanine or 2-methylalanine, is an amino acid with the structural formula is H2N-C2-COOH. It is contained in some antibiotics of fungal origin, e.g. alamethicin and some lantibiotics. It is not one of the proteinogenic amino acids and...
.
Lantibiotics are produced by a large number of Gram-positive bacteria such as Streptococcus
Streptococcus
Streptococcus is a genus of spherical Gram-positive bacteria belonging to the phylum Firmicutes and the lactic acid bacteria group. Cellular division occurs along a single axis in these bacteria, and thus they grow in chains or pairs, hence the name — from Greek στρεπτος streptos, meaning...
and Streptomyces
Streptomyces
Streptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinobacteria, streptomycetes are gram-positive, and have genomes with high guanine and cytosine content...
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
Posttranslational modification
Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....
. The lantibiotics are a class of more extensively modified bacteriocins, also called Class I bacteriocins. (Bacteriocins for which disulfide bond
Disulfide bond
In chemistry, a disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry...
s are the only modification to the peptide are Class II bacteriocin
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....
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
Cheese is a generic term for a diverse group of milk-based food products. Cheese is produced throughout the world in wide-ranging flavors, textures, and forms....
.
Nisin
Nisin
Nisin is a polycyclic antibacterial peptide with 34 amino acid residues used as a food preservative. It contains the uncommon amino acids lanthionine , methyllanthionine , didehydroalanine and didehydroaminobutyric acid . These unusual amino acids are introduced by posttranslational modification...
and epidermin are members of a family of lantibiotics that bind to a cell wall precursor lipid component of target bacteria and disrupt cell wall production. The duramycin family of lantibiotics binds phosphoethanolamine in the membranes
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
of its target cells and seem to disrupt several physiological functions.
History
The name lantibiotics was introduced in 1988 as an abbreviation for "lanthionineLanthionine
Lanthionine is a nonproteinogenic amino acid with the chemical formula . As the monosulfide analog of cystine, lanthionine is composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage...
-containing peptide antibiotics". The first structures of these antimicrobial
Antimicrobial
An anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes or prevent the growth of microbes...
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
Nisin
Nisin is a polycyclic antibacterial peptide with 34 amino acid residues used as a food preservative. It contains the uncommon amino acids lanthionine , methyllanthionine , didehydroalanine and didehydroaminobutyric acid . These unusual amino acids are introduced by posttranslational modification...
have been used auspiciously for food preservation and have yet to encounter significant bacterial resistance. These attributes of lantibiotics have led to more detailed research into their structures and biosynthetic pathways
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
.
Classification
- Type A lantibiotics are long flexible molecules - e.g. nisinNisinNisin is a polycyclic antibacterial peptide with 34 amino acid residues used as a food preservative. It contains the uncommon amino acids lanthionine , methyllanthionine , didehydroalanine and didehydroaminobutyric acid . These unusual amino acids are introduced by posttranslational modification...
, subtilin, epidermin. Subgroup AI includes mutacin II; subgroup AII includes mutacin I and III. - Type B lantibiotics are globular - e.g. mersacidin, actagardine, and cinnamycin.
Biosynthesis
The biosynthesis is interesting. They are synthesised with a leader polypeptide sequence which is only removed during the transport of the molecule out of the synthesising cell. They are synthesized by ribosomes, which distinguishes them from antibiotics, which are synthesized by enzymes.Mechanism of action
Lantibiotics show substantial specificity for some components (e.g. lipid II) of bacterial cell membranes especially of Gram-positive bacteria. Type A lantibiotics kill rapidly by pore formation, type B lantibiotics inhibit peptidoglycan biosynthesis. for discussion of mechanism of action. They are active in very low concentrations.Application
Lantibiotics are produced by Gram-positive bacteria and show strong antimicrobial action towards a wide range of other Gram-positive bacteria.As such they have become attractive candidates for use in food preservation
Food preservation
Food preservation is the process of treating and handling food to stop or slow down spoilage and thus allow for longer storage....
(by inhibiting pathogens that cause food spoilage) and the pharmaceutical industry (to prevent or fight infections in humans or animals).
One type B lantibiotic NVB302 entered clinical trials in 2011 for use against Clostridium difficile
Clostridium difficile
Clostridium difficile , also known as "CDF/cdf", or "C...
.
External links
- Calculated positions of lantibiotics in membrane
- Characterization of Mutacin 1140. 2002 PhD thesis by James L Smith
- Biosynthesis of Nisin. Seigers et al. J. Biol. Chem., May 24, 1996; 271(21): 12294 - 12301.
- Biosynthesis and biology of L'. Sahl et al. 1995 (abstract) BROKEN
- Biosynthesis and biology of Lantibiotics..... Sahl et al. EJB June 1995 (abstract and link to full text 27p PDF) BROKEN
- Molecular biology on all the Bacillus subtilis antibiotics. T. Stein. 13pp