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 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 bonds are the only modification to the peptide are
Class II bacteriocins.)
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
lipid II, 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.
History
The name lantibiotics was introduced in 1988 as an abbreviation for "lanthionine-containing peptide antibiotics".[1] 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.
Classification
Type A lantibiotics are long flexible molecules - e.g.,
nisin, bisin,
subtilin,
epidermin,
gallidermin[2] Subgroup AI includes
mutacin II; subgroup AII includes mutacin I and III.
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
ribosomes, which distinguishes them from most natural antibiotics.[9] There are four known enzymes (lanthipeptide synthetases) responsible for producing lanthionine rings.[10][11]
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.[12] They are active in very low concentrations.[13]
Application
Food preservation
Lantibiotics are produced by Gram-positive bacteria and show strong antimicrobial action toward a wide range of other Gram-positive bacteria.[14] As such, they have become attractive candidates for use in
food preservation (by
inhibitingpathogens that cause food spoilage) and the
pharmaceutical industry (to prevent or fight infections in humans or animals).[14]
Clinical antibiotic
One type known as B lantibiotic
NVB302 entered phase 1 clinical trials in 2011 for use against Clostridium difficile,[15] and reported good results in 2012.[16]
Databases
BACTIBASE is an open-access database for bacteriocins including lantibiotics.[17][18] LANTIBASE is a lantibiotic specific resource.[19]
References
^Chatterjee C, Paul M, Xie L, van der Donk WA (February 2005). "Biosynthesis and mode of action of lantibiotics". Chem. Rev. 105 (2): 633–84.
doi:
10.1021/cr030105v.
PMID15700960.
^
abKellner R, Jung G, Hörner T, Zähner H, Schnell N, Entian KD, Götz F (October 1988). "Gallidermin: a new lanthionine-containing polypeptide antibiotic". Eur. J. Biochem. 177 (1): 53–9.
doi:
10.1111/j.1432-1033.1988.tb14344.x.
PMID3181159.