Lantibiotics


Lantibiotics are a class of polycyclic peptide antibiotics that contain the characteristic thioether amino acids lanthionine or methyllanthionine, as well as the unsaturated amino acids dehydroalanine, and 2-aminoisobutyric acid. 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 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.
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". 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

Some contain 2 peptides, e.g. haloduracin.

Examples

LantibioticType# of
residues		# of
thioether links		Other
links		refs
nisin
subtilin		A3450
gallidermin
epidermin		A2131
mersacidinB204
actagardineB1940
cinnamycin
duramycin		B1931
Sublancin 168?3712
Plantaricin CB2740

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

Mechanism of action

Lantibiotics show substantial specificity for some components of bacterial cell membranes 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 and the pharmaceutical industry.

Veterinary antibiotic

Duramycin is used for chickens.

Clinical antibiotic

One type known as B lantibiotic NVB302 entered phase 1 clinical trials in 2011 for use against Clostridium difficile, and reported good results in 2012.

Databases

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