Production of the Novel Two-Peptide Lantibiotic Lichenicidin by Bacillus licheniformis DSM 13 英文参考文献.docVIP

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Production of the Novel Two-Peptide Lantibiotic Lichenicidin by Bacillus licheniformis DSM 13 英文参考文献.doc

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Production of the Novel Two-Peptide Lantibiotic Lichenicidin by Bacillus licheniformis DSM 13 英文参考文献

ProductionoftheNovelTwo-PeptideLantibiotic LichenicidinbyBacilluslicheniformisDSM13 JasminDischinger,MichaeleJosten,ChristianeSzekat,Hans-GeorgSahl,GabrieleBierbaum* InstituteofMedicalMicrobiology,ImmunologyandParasitology(IMMIP),UniversityofBonn,Bonn,Germany Abstract Background: Lantibiotics are small microbial peptide antibiotics that are characterized by the presence of the thioether aminoacidslanthionineandmethyllanthionine.Lantibioticspossessstructuralgeneswhichencodeinactiveprepeptides. Duringmaturation,theprepeptideundergoesposttranslationalmodificationsincludingtheintroductionofrareaminoacids aslanthionineandmethyllanthioneaswellastheproteolyticremovaloftheleader.Thestructuralgene(lanA)aswellasthe othergeneswhichareinvolvedinlantibioticmodification(lanM,lanB,lanC,lanP),regulation(lanR,lanK),export(lanT(P)) andimmunity(lanEFG)areorganizedinbiosyntheticgeneclusters. Methodology/PrincipalFindings:SequencecomparisonsintheNCBIdatabaseshowedthatBacilluslicheniformisDSM13 harbours a putative lantibiotic gene cluster which comprises two structural genes (licA1, licA2) and two modification enzymes(licM1,licM2)inadditionto10ORFsthatshowsequencesimilaritiestoproteinsinvolvedinlantibioticproduction. Aheatlabileantimicrobialactivitywasdetectedintheculturesupernatantandaheatstabileactivitywaspresentinthe isopropanolcellwashextractofthisstrain.Inagarwelldiffusionassaysbothfractionsexhibitedslightlydifferentactivity spectraagainstGram-positivebacteria.Inordertodemonstratetheconnectionbetweenthelantibioticgeneclusterand oneoftheantibacterialactivities,twoBacilluslicheniformisDSM13mutantstrainsharbouringinsertionsinthestructural genesofthemodificationenzymeslicM1andlicM2wereconstructed.Thesestrainswerecharacterizedbyalossofactivity in the isopropanol extract and substractive MALDI-TOF predicted masses of 3020.6 Da and 3250.6 Da for the active peptides. Conclusions/Significance:Inconclusion,B.licheniformisDSM13producesanantimicrobialsubstancethatrepresentsthe two-peptide lan