Lantibiotics
| Identifiers | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Symbol | Gallidermin | ||||||||
| Pfam | PF02052 | ||||||||
| InterPro | IPR006079 | ||||||||
| SCOP | 1g5q | ||||||||
| SUPERFAMILY | 1g5q | ||||||||
| TCDB | 1.C.20 | ||||||||
| OPM family | 170 | ||||||||
| OPM protein | 1mqy | ||||||||
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Lantibiotics are a class of peptide antibiotics 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 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 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.
Contents |
[edit] 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.
[edit] Classification
- Type A lantibiotics are long flexible molecules - e.g. nisin, 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.
[edit] 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.
[edit] 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.[2] for discussion of mechanism of action. They are active in very low concentrations.[3]
[edit] Application
Lantibiotics are produced by Gram-positive bacteria and show strong antimicrobial action towards a wide range of other Gram-positive bacteria.[4] 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).[5]
One type B lantibiotic NVB302 entered clinical trials in 2011 for use against Clostridium difficile.[6]
[edit] Database
BACTIBASE is an open-access database for bacteriocins including lantibiotics.[7][8]
[edit] References
- ^ W. van der Donk et al. Chem. Rev. (2005) 105, 633 - 683
- ^ Brötz H and Sahl H-G. (2000.). "New insights into the mechanism of action of lantibiotics—diverse biological effects by binding to the same molecular target.". Journal of Antimicrobial Chemotherapy (2000) 46, 1-6. 46 (1): 1–6. doi:10.1093/jac/46.1.1. PMID 10882681. http://jac.oxfordjournals.org/cgi/content/full/46/1/1.
- ^ Cotter, Hill, Ross (2005). Bacterial Lantibiotics: Strategies to Improve Therapeutic Potential. 6. Current Protein and Peptide Science. pp. 61–75. http://www.bentham.org/cpps/sample/cpps6-1/0007K.pdf.
- ^ C. van Kraaij et al., Nat. Prod. Rep. (1999), 16, 575 - 587.
- ^ Van Kraaij, C; De Vos, WM; Siezen, RJ; Kuipers, OP (1999). "Lantibiotics: biosynthesis, mode of action and applications". Natural product reports 16 (5): 575–87. PMID 10584332.
- ^ "New antibiotic compound enters phase I clinical trial". 3 Nov 2011. http://www.wellcome.ac.uk/News/2011/News/WTVM053339.htm.
- ^ Hammami R, Zouhir A, Ben Hamida J, Fliss I (2007). "BACTIBASE: a new web-accessible database for bacteriocin characterization". BMC Microbiology 7: 89. doi:10.1186/1471-2180-7-89. PMC 2211298. PMID 17941971. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2211298.
- ^ Hammami R, Zouhir A, Le Lay C, Ben Hamida J, Fliss I (2010). "BACTIBASE second release: a database and tool platform for bacteriocin characterization". BMC Microbiology 10: 22. doi:10.1186/1471-2180-10-22. PMC 2824694. PMID 20105292. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2824694.
[edit] External links
- Complete list of lantibiotics at BACTIBASE
- 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
- Hans-Georg Sahl and Gabriele Bierbaum (1998). "LANTIBIOTICS: Biosynthesis and Biological Activities of Uniquely Modified Peptides from Gram-Positive Bacteria". Annual Review of Microbiology 52: 41–79. doi:10.1146/annurev.micro.52.1.41. PMID 9891793. http://www.annualreviews.org/doi/abs/10.1146/annurev.micro.52.1.41?journalCode=micro.
- Molecular biology on all the Bacillus subtilis antibiotics. T. Stein. 13pp
