Biology:Lantibiotics
| Gallidermin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Gallidermin | ||||||||
| Pfam | PF02052 | ||||||||
| InterPro | IPR006079 | ||||||||
| SCOP2 | 1mqy / SCOPe / SUPFAM | ||||||||
| TCDB | 1.C.20 | ||||||||
| OPM superfamily | 161 | ||||||||
| OPM protein | 1mqy | ||||||||
| |||||||||
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 (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.
- Type B lantibiotics are globular - e.g., mersacidin.[3][4] actagardine, duramycin, and cinnamycin.[5]
Some contain 2 peptides, e.g. haloduracin.[6]
Examples
| Lantibiotic | Type | # of residues |
# of thioether links |
Other links[clarification needed] |
refs |
|---|---|---|---|---|---|
| nisin subtilin |
A | 34 | 5 | 0 | |
| gallidermin epidermin |
A | 21 | 3 | 1 | [2] |
| mersacidin | B | 20 | 4 | [3] | |
| actagardine | B | 19 | 4 | 0 | |
| cinnamycin duramycin |
B | 19 | 3 | 1 | [5] |
| sublancin 168 | ? | 37 | 1 | 2 | [7] |
| plantaricin C | B | 27 | 4 | 0 |
(Sublancin may be an S-linked glycopeptide).[8]
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.[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 inhibiting pathogens 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
- ↑ "Biosynthesis and mode of action of lantibiotics". Chem. Rev. 105 (2): 633–84. February 2005. doi:10.1021/cr030105v. PMID 15700960.
- ↑ 2.0 2.1 "Gallidermin: a new lanthionine-containing polypeptide antibiotic". Eur. J. Biochem. 177 (1): 53–9. October 1988. doi:10.1111/j.1432-1033.1988.tb14344.x. PMID 3181159.
- ↑ 3.0 3.1 "The lantibiotic mersacidin is a strong inducer of the cell wall stress response of Staphylococcus aureus". BMC Microbiol. 8: 186. 2008. doi:10.1186/1471-2180-8-186. PMID 18947397.
- ↑ "Mode of action of the lantibiotic mersacidin: inhibition of peptidoglycan biosynthesis via a novel mechanism?". Antimicrob. Agents Chemother. 39 (3): 714–9. March 1995. doi:10.1128/AAC.39.3.714. PMID 7793878.
- ↑ 5.0 5.1 "Cinnamycin (Ro 09-0198) promotes cell binding and toxicity by inducing transbilayer lipid movement". J. Biol. Chem. 278 (5): 3204–9. January 2003. doi:10.1074/jbc.M210347200. PMID 12446685.
- ↑ "Structure-activity relationship studies of the two-component lantibiotic haloduracin". Chem. Biol. 15 (10): 1035–45. October 2008. doi:10.1016/j.chembiol.2008.07.020. PMID 18940665.
- ↑ Stein T (May 2005). "Bacillus subtilis antibiotics: structures, syntheses and specific functions". Mol. Microbiol. 56 (4): 845–57. doi:10.1111/j.1365-2958.2005.04587.x. PMID 15853875.
- ↑ "Sublancin is not a lantibiotic but an S-linked glycopeptide". Nat. Chem. Biol. 7 (2): 78–80. February 2011. doi:10.1038/nchembio.509. PMID 21196935.
- ↑ "Biosynthesis of lantibiotic nisin. Posttranslational modification of its prepeptide occurs at a multimeric membrane-associated lanthionine synthetase complex". J. Biol. Chem. 271 (21): 12294–301. May 1996. doi:10.1074/jbc.271.21.12294. PMID 8647829.
- ↑ Goto, Y; Li, B; Claesen, J; Shi, Y; Bibb, MJ; van der Donk, WA (2010). "Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights". PLOS Biology 8 (3): e1000339. doi:10.1371/journal.pbio.1000339. PMID 20351769.
- ↑ Zhang, Q; Yu, Y; Vélasquez, JE; van der Donk, WA (2012). "Evolution of lanthipeptide synthetases". Proceedings of the National Academy of Sciences 109 (45): 18361–6. doi:10.1073/pnas.1210393109. PMID 23071302. Bibcode: 2012PNAS..10918361Z.
- ↑ "New insights into the mechanism of action of lantibiotics—diverse biological effects by binding to the same molecular target". Journal of Antimicrobial Chemotherapy 46 (1): 1–6. 2000. doi:10.1093/jac/46.1.1. PMID 10882681.
- ↑ Cotter, Hill, Ross (2005). "Bacterial Lantibiotics: Strategies to Improve Therapeutic Potential". Current Protein & Peptide Science 6 (1): 61–75. doi:10.2174/1389203053027584. PMID 15638769. http://www.bentham.org/cpps/sample/cpps6-1/0007K.pdf. Retrieved 2007-06-01.
- ↑ 14.0 14.1 "Lantibiotics: biosynthesis, mode of action and applications". Nat Prod Rep 16 (5): 575–87. October 1999. doi:10.1039/a804531c. PMID 10584332.
- ↑ "New antibiotic compound enters phase I clinical trial". Press Release. Wellcome Trust. 2011-11-03. http://www.wellcome.ac.uk/News/2011/News/WTVM053339.htm.
- ↑ Parker S (2012-08-06). "Novacta Biosystems Limited completes Phase I study of NVB302 against C. difficile infection in healthy volunteers". Press Release. Celtic Pharma Holding. http://www.celticpharmaholdings.com/component/k2/item/5-novacta-biosystems-limited-completes-phase-i-study-of-nvb302-against-c-difficile-infection-in-healthy-volunteers.
- ↑ "BACTIBASE: a new web-accessible database for bacteriocin characterization". BMC Microbiology 7: 89. 2007. doi:10.1186/1471-2180-7-89. PMID 17941971.
- ↑ "BACTIBASE second release: a database and tool platform for bacteriocin characterization". BMC Microbiology 10: 22. 2010. doi:10.1186/1471-2180-10-22. PMID 20105292.
- ↑ "DBT Centre for Bioinformatics Presidency University, Kolkata". http://bioinfo-presiuniv.edu.in/lantibase_about.php.
Further reading
- "The genetics of lantibiotic biosynthesis". BioEssays 17 (9): 793–802. September 1995. doi:10.1002/bies.950170909. PMID 8763832.
- "Biosynthesis and biological activities of lantibiotics with unique post-translational modifications". Eur. J. Biochem. 230 (3): 827–53. June 1995. doi:10.1111/j.1432-1033.1995.0827g.x. PMID 7601145.
- "Lantibiotics: biosynthesis and biological activities of uniquely modified peptides from gram-positive bacteria". Annu. Rev. Microbiol. 52: 41–79. 1998. doi:10.1146/annurev.micro.52.1.41. PMID 9891793.
- Stein T (May 2005). "Bacillus subtilis antibiotics: structures, syntheses and specific functions". Mol. Microbiol. 56 (4): 845–57. doi:10.1111/j.1365-2958.2005.04587.x. PMID 15853875.
- Smith JL (2002). Structural and functional characterization of the lantibiotic mutacin (PDF) (Ph.D.). University of Florida.
External links
- Lantibase, a database of lantibiotics
- "Complete list of lantibiotics". BACTIBASE Database. http://bactibase.hammamilab.org/bacteriocinslist.php?Class=lantibiotic.
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