Lantibiotics

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

Lantibiotics are well studied because of the commercial use of these bacteria in the food industry for making dairy products such as cheese. 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 for which disulfide bonds are the only modification to the peptide are Class II bacteriocins. Most bacteriocins are biologically active single-chain peptides. Some are only active as partners with a second peptide (see Class IIb, below).

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.

History

The name Lantibiotics was introduced in 1988 as an abbreviation for "Lanthionine-containing peptide antibiotics" [ W. van der Donk et al. Chem. Rev. (2005) 105, 633 - 683] . The first structures of these antimicrobial agents were produced by pioneering work by Gross and Morell in the late sixties and early seventies, 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 - eg Nisin, subtilin, epidermin. Subgroup AI includes Mutacin II, subgroup AII includes Mutacin I & III.
*Type B Lantibiotics are globular - eg mersacidin, actagardine, 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.

Mechanism of action

Lantibiotics show substantial specificity for some components (eg lipid II) of bacterial cell membranes especially of Gram positive bacteria. Type A kill rapidly by pore formation, type B inhibit peptidoglycan biosynthesis. See Brotz and Sahl. JAC (2000) 46, 1-6 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 [ C. van Kraaij et al, Nat. Prod. Rep. (1999), 16, 575 - 587.] . 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). See C. van Kraaij et al, Nat. Prod. Rep. (1999), 16, 583 - 584 for more detailed discusion of the pharmaceutical application of lantibiotics.

References

External links

* [http://www.bentham.org/cpps/sample/cpps6-1/0007K.pdf Therapeutic potential. Cross et al 2005]
* [http://opm.phar.umich.edu/families.php?superfamily=170 Calculated positions of lantibiotics in membrane]
* [http://etd.fcla.edu/UF/UFE1001183/smith_jl.pdf Characterization of Mutacin 1140. 2002 PhD thesis by James L Smith ]
* [http://www.jbc.org/cgi/reprint/271/21/12294.pdf Biosynthesis of Nisin. Seigers et al. J. Biol. Chem., May 24, 1996; 271(21): 12294 - 12301.]
* [http://content.febsjournal.org/cgi/content/abstract/230/3/827 Biosynthesis and biology of L'. Sahl et al 1995 (abstract) BROKEN ]
* [http://www.blackwell-synergy.com/doi/abs/10.1111/j.1432-1033.1995.tb20627.x Biosynthesis and biology of Lantibiotics..... Sahl et al EJB June 1995 (abstract and link to full text 27p PDF) ]
* [http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2958.2005.04587.x Molecular biology on all the Bacillus subtilis antibiotics. T. Stein. 13pp ]