# Lantibiotics > Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Lantibiotics > Markdown URL: https://mediated.wiki/source/Lantibiotics.md > Source: https://en.wikipedia.org/wiki/Lantibiotics > Source revision: 1314034763 > License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/) {{Short description|Class of chemical compounds}} {{Infobox protein family | Symbol = Gallidermin | Name = Gallidermin | image = | width = | caption = | Pfam= PF02052 | InterPro= IPR006079 | SMART= | Prosite = | SCOP = 1mqy | TCDB = 1.C.20 | OPM family= 161 | OPM protein= 1mqy | PDB= }} '''Lantibiotics''' are a class of poly[cyclic peptide](/source/cyclic_peptide) [antibiotic](/source/antibiotic)s that contain the characteristic [thioether](/source/thioether) [amino acids](/source/amino_acids) [lanthionine](/source/lanthionine) or [methyllanthionine](/source/methyllanthionine), as well as the [unsaturated](/source/Saturated_and_unsaturated_compounds) amino acids [dehydroalanine](/source/dehydroalanine), and [2-aminoisobutyric acid](/source/2-Aminoisobutyric_acid). They belong to [ribosomally synthesized and post-translationally modified peptides](/source/Ribosomally_synthesized_and_post-translationally_modified_peptides). Lanthionine is composed of two [alanine](/source/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](/source/Gram-positive_bacteria) such as ''[Streptococcus](/source/Streptococcus)'' and ''[Streptomyces](/source/Streptomyces)'' to attack other Gram-positive bacteria, and as such, they are considered a member of the [bacteriocins](/source/bacteriocins). Bacteriocins are classified according to their extent of [posttranslational modification](/source/posttranslational_modification). The lantibiotics are a class of more extensively modified bacteriocins, also called '''Class I bacteriocins'''. (Bacteriocins for which [disulfide bond](/source/disulfide_bond)s are the only modification to the peptide are [Class II bacteriocin](/source/Class_II_bacteriocin)s.) Lantibiotics are well studied because of the commercial use of these bacteria in the food industry for making dairy products such as [cheese](/source/cheese). [Nisin](/source/Nisin) and [epidermin](/source/epidermin) are members of a family of lantibiotics that bind to [lipid II](/source/lipid_II), a [cell wall](/source/Cell_wall) precursor lipid component of target bacteria and disrupt cell wall production. The [duramycin](/source/duramycin) family of lantibiotics binds [phosphoethanolamine](/source/phosphoethanolamine) in the [membranes](/source/cell_membrane) 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".{{cite journal |vauthors=Chatterjee C, Paul M, Xie L, van der Donk WA | title = Biosynthesis and mode of action of lantibiotics | journal = Chem. Rev. | volume = 105 | issue = 2 | pages = 633–84 |date=February 2005 | pmid = 15700960 | doi = 10.1021/cr030105v }} The first structures of these [antimicrobial](/source/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](/source/nisin) have been used auspiciously for food preservation and have yet to encounter significant [bacterial resistance](/source/Antibiotic_resistance). These attributes of lantibiotics have led to more detailed research into their structures and [biosynthetic pathways](/source/biosynthesis). == Classification == *Type A lantibiotics are long flexible molecules - e.g., [nisin](/source/nisin), bisin, [subtilin](/source/subtilin), [epidermin](/source/epidermin), [gallidermin](/source/gallidermin){{cite journal |vauthors=Kellner R, Jung G, Hörner T, Zähner H, Schnell N, Entian KD, Götz F | title = Gallidermin: a new lanthionine-containing polypeptide antibiotic | journal = Eur. J. Biochem. | volume = 177 | issue = 1 | pages = 53–9 |date=October 1988 | pmid = 3181159 | doi =10.1111/j.1432-1033.1988.tb14344.x }} Subgroup AI includes [mutacin](/source/mutacin) II; subgroup AII includes mutacin I and III. *Type B lantibiotics are globular - e.g., [mersacidin](/source/mersacidin).{{cite journal |vauthors=Sass P, Jansen A, Szekat C, Sass V, Sahl HG, Bierbaum G | title = The lantibiotic mersacidin is a strong inducer of the cell wall stress response of Staphylococcus aureus | journal = BMC Microbiol. | volume = 8| page = 186 | year = 2008 | pmid = 18947397 | pmc = 2592248 | doi = 10.1186/1471-2180-8-186 | doi-access = free }}{{cite journal |vauthors=Brötz H, Bierbaum G, Markus A, Molitor E, Sahl HG | title = Mode of action of the lantibiotic mersacidin: inhibition of peptidoglycan biosynthesis via a novel mechanism? | journal = Antimicrob. Agents Chemother. | volume = 39 | issue = 3 | pages = 714–9 |date=March 1995 | pmid = 7793878 | pmc = 162610 | doi =10.1128/AAC.39.3.714 }} [actagardine](/source/actagardine), [duramycin](/source/duramycin), and [cinnamycin](/source/cinnamycin).{{cite journal |vauthors=Makino A, Baba T, Fujimoto K, Iwamoto K, Yano Y, Terada N, Ohno S, Sato SB, Ohta A, Umeda M, Matsuzaki K, Kobayashi T | title = Cinnamycin (Ro 09-0198) promotes cell binding and toxicity by inducing transbilayer lipid movement | journal = J. Biol. Chem. | volume = 278 | issue = 5 | pages = 3204–9 |date=January 2003 | pmid = 12446685 | doi = 10.1074/jbc.M210347200 | doi-access = free }} Some contain 2 peptides, e.g. [haloduracin](/source/haloduracin).{{cite journal |vauthors=Cooper LE, McClerren AL, Chary A, van der Donk WA | title = Structure-activity relationship studies of the two-component lantibiotic haloduracin | journal = Chem. Biol. | volume = 15 | issue = 10 | pages = 1035–45 |date=October 2008 | pmid = 18940665 | pmc = 2633096 | doi = 10.1016/j.chembiol.2008.07.020 }} === Examples === {| class="wikitable" |- ! Lantibiotic !! Type !! # of
residues !! # of
thioether links !! Other
links{{clarify|date=December 2016}} !! refs |- | nisin
subtilin || A || 34 || 5 || 0 || |- | gallidermin
epidermin || A || 21 || 3 || 1 || |- | mersacidin || B || 20 || 4 || || |- | actagardine || B || 19 || 4 || 0 || |- | cinnamycin
duramycin || B || 19 || 3 || 1 || |- | [sublancin](/source/sublancin) 168 || ? || 37 || 1 || 2 || {{cite journal | author = Stein T | title = Bacillus subtilis antibiotics: structures, syntheses and specific functions | journal = Mol. Microbiol. | volume = 56 | issue = 4 | pages = 845–57 |date=May 2005 | pmid = 15853875 | doi = 10.1111/j.1365-2958.2005.04587.x | s2cid = 20144405 | doi-access = free }} |- | [plantaricin C](/source/plantaricin_C) || B || 27 || 4 || 0 || |- |} (Sublancin may be an S-linked [glycopeptide](/source/glycopeptide)).{{cite journal |vauthors=Oman TJ, Boettcher JM, Wang H, Okalibe XN, van der Donk WA | title = Sublancin is not a lantibiotic but an S-linked glycopeptide | journal = Nat. Chem. Biol. | volume = 7 | issue = 2 | pages = 78–80 |date=February 2011 | pmid = 21196935 | pmc = 3060661 | doi = 10.1038/nchembio.509 }} == 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 [ribosome](/source/ribosome)s, which distinguishes them from most natural antibiotics.{{cite journal |vauthors=Siegers K, Heinzmann S, Entian KD | title = Biosynthesis of lantibiotic nisin. Posttranslational modification of its prepeptide occurs at a multimeric membrane-associated lanthionine synthetase complex | journal = J. Biol. Chem. | volume = 271 | issue = 21 | pages = 12294–301 |date=May 1996 | pmid = 8647829 | doi = 10.1074/jbc.271.21.12294| doi-access = free }} There are four known enzymes (lanthipeptide synthetases) responsible for producing lanthionine rings.{{Cite journal | pmid = 20351769 | year = 2010 | last1 = Goto | first1 = Y | last2 = Li | first2 = B | last3 = Claesen | first3 = J | last4 = Shi | first4 = Y | last5 = Bibb | first5 = MJ | last6 = van der Donk | first6 = WA | title = Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights | volume = 8 | issue = 3 | article-number = e1000339 | doi = 10.1371/journal.pbio.1000339 | pmc = 2843593 | journal = PLOS Biology | doi-access = free }}{{Cite journal | pmid = 23071302 | year = 2012 | last1 = Zhang | first1 = Q | last2 = Yu | first2 = Y | last3 = Vélasquez | first3 = JE | last4 = van der Donk | first4 = WA | title = Evolution of lanthipeptide synthetases| volume = 109 | issue = 45 | pages = 18361–6 | doi = 10.1073/pnas.1210393109 | pmc = 3494888 | journal = Proceedings of the National Academy of Sciences| bibcode = 2012PNAS..10918361Z | doi-access = free }} == Mechanism of action == Lantibiotics show substantial specificity for some components (e.g., [lipid II](/source/lipid_II)) of bacterial [cell membranes](/source/cell_membranes) especially of Gram-positive bacteria. Type A lantibiotics kill rapidly by pore formation, type B lantibiotics inhibit peptidoglycan biosynthesis.{{cite journal |vauthors=Brötz H, Sahl HG|year=2000 |title=New insights into the mechanism of action of lantibiotics—diverse biological effects by binding to the same molecular target |journal=[Journal of Antimicrobial Chemotherapy](/source/Journal_of_Antimicrobial_Chemotherapy) |pmid=10882681 |doi=10.1093/jac/46.1.1 |volume=46 |issue=1 |pages=1–6|doi-access=free }} They are active in very low concentrations.{{cite journal |url=http://www.bentham.org/cpps/sample/cpps6-1/0007K.pdf |title=Bacterial Lantibiotics: Strategies to Improve Therapeutic Potential |author=Cotter, Hill, Ross |journal=Current Protein & Peptide Science |year=2005 |volume=6 |issue=1 |pages=61–75 |doi=10.2174/1389203053027584 |pmid=15638769 |access-date=2007-06-01 |archive-url=https://web.archive.org/web/20070928025815/http://www.bentham.org/cpps/sample/cpps6-1/0007K.pdf |archive-date=2007-09-28 }} == 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](/source/food_preservation) (by [inhibiting](/source/Enzyme_inhibitors) [pathogens](/source/pathogens) that cause food spoilage) and the [pharmaceutical industry](/source/pharmaceutical_industry) (to prevent or fight infections in humans or animals).{{cite journal |vauthors=van Kraaij C, de Vos WM, Siezen RJ, Kuipers OP | title = Lantibiotics: biosynthesis, mode of action and applications | journal = Nat Prod Rep | volume = 16 | issue = 5 | pages = 575–87 |date=October 1999 | pmid = 10584332 | doi =10.1039/a804531c | citeseerx =10.1.1.546.6212 }} === Clinical antibiotic === One type known as B lantibiotic [NVB302](/source/NVB302) entered phase 1 clinical trials in 2011 for use against ''[Clostridioides difficile](/source/Clostridioides_difficile_infection)'',{{cite web | url = http://www.wellcome.ac.uk/News/2011/News/WTVM053339.htm | title = New antibiotic compound enters phase I clinical trial | date = 2011-11-03 | work = Press Release | publisher = Wellcome Trust }} and reported good results in 2012.{{cite web | url = http://www.celticpharmaholdings.com/component/k2/item/5-novacta-biosystems-limited-completes-phase-i-study-of-nvb302-against-c-difficile-infection-in-healthy-volunteers | title = Novacta Biosystems Limited completes Phase I study of NVB302 against C. difficile infection in healthy volunteers | author = Parker S | date = 2012-08-06 | work = Press Release | publisher = Celtic Pharma Holding | access-date = 2013-03-23 | archive-url = https://web.archive.org/web/20130901115657/http://celticpharmaholdings.com/component/k2/item/5-novacta-biosystems-limited-completes-phase-i-study-of-nvb302-against-c-difficile-infection-in-healthy-volunteers | archive-date = 2013-09-01 }} == Databases == BACTIBASE is an open-access database for bacteriocins including lantibiotics.{{cite journal |title=BACTIBASE: a new web-accessible database for bacteriocin characterization |vauthors=Hammami R, Zouhir A, Ben Hamida J, Fliss I |journal=BMC Microbiology |year=2007 |volume=7 |page=89 |pmid=17941971 |doi=10.1186/1471-2180-7-89 |pmc=2211298 |doi-access=free }}{{cite journal |title=BACTIBASE second release: a database and tool platform for bacteriocin characterization |vauthors=Hammami R, Zouhir A, Le Lay C, Ben Hamida J, Fliss I |journal=BMC Microbiology |year=2010 |volume=10 |page=22 |pmid=20105292 |doi=10.1186/1471-2180-10-22 |pmc=2824694 |doi-access=free }} LANTIBASE is a lantibiotic specific resource.{{cite web |url=http://bioinfo-presiuniv.edu.in/lantibase_about.php |title=DBT Centre for Bioinformatics Presidency University, Kolkata |access-date=2013-07-25 |archive-url=https://web.archive.org/web/20130815113818/http://bioinfo-presiuniv.edu.in/lantibase_about.php |archive-date=2013-08-15 }} ==References== {{reflist|35em}} == Further reading == {{refbegin|35em}} * {{cite journal |vauthors=Jack R, Bierbaum G, Heidrich C, Sahl HG | title = The genetics of lantibiotic biosynthesis | journal = BioEssays | volume = 17 | issue = 9 | pages = 793–802 |date=September 1995 | pmid = 8763832 | doi = 10.1002/bies.950170909 | s2cid = 32393523 }} * {{cite journal |vauthors=Sahl HG, Jack RW, Bierbaum G | title = Biosynthesis and biological activities of lantibiotics with unique post-translational modifications | journal = Eur. J. Biochem. | volume = 230 | issue = 3 | pages = 827–53 |date=June 1995 | pmid = 7601145 | doi = 10.1111/j.1432-1033.1995.0827g.x | doi-access = free }} * {{cite journal |vauthors=Sahl HG, Bierbaum G | title = Lantibiotics: biosynthesis and biological activities of uniquely modified peptides from gram-positive bacteria | journal = Annu. Rev. Microbiol. | volume = 52 | pages = 41–79 | year = 1998 | pmid = 9891793 | doi = 10.1146/annurev.micro.52.1.41 }} * {{cite journal | author = Stein T | title = Bacillus subtilis antibiotics: structures, syntheses and specific functions | journal = Mol. Microbiol. | volume = 56 | issue = 4 | pages = 845–57 |date=May 2005 | pmid = 15853875 | doi = 10.1111/j.1365-2958.2005.04587.x | s2cid = 20144405 | doi-access = free }} * {{Cite thesis | type= Ph.D. | title = Structural and functional characterization of the lantibiotic mutacin | url = http://etd.fcla.edu/UF/UFE1001183/smith_jl.pdf | author = Smith JL | year = 2002 | publisher = University of Florida }} {{refend}} ==External links== *[https://lantibase.weebly.com/ Lantibase], a database of lantibiotics * {{cite web | url = http://bactibase.hammamilab.org/bacteriocinslist.php?Class=lantibiotic | title = Complete list of lantibiotics | work = BACTIBASE Database}} Category:Lantibiotics Category:Peripheral membrane proteins --- Adapted from the Wikipedia article [Lantibiotics](https://en.wikipedia.org/wiki/Lantibiotics) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Lantibiotics?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.