羊毛硫细菌素变体及其生物活性研究进展
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摘要
羊毛硫细菌素是由细菌核糖体上合成并经翻译后加工修饰而成的一类抗菌肽。已经在多种G+细菌中发现有羊毛硫细菌素,大多对G+细菌有抑菌作用。羊毛硫细菌素的基因工程无法从单一的表达羊毛硫细菌素结构基因获得高活性的成熟羊毛硫细菌素。本研究综述了羊毛硫细菌素前体分子定向位点突变后,由修饰酶重新识别和修饰可产生结构变异的可分泌的变体分子和无法分泌的变体分子,对羊毛硫细菌素分子突变位点进行了分类和归纳,并总结了羊毛硫细菌素分子突变位点与其生物活性的关系。在现有羊毛硫细菌素应用成果有限的条件下,对于工程改造羊毛硫细菌素和增强其抑菌活性具有重要意义。
Lantibiotics is a kind of antimicrobial peptides synthesized on bacterial ribosome and modified by post-translation processing, have been found in a variety of G+bacteria, most of which have inhibitory effects on G+bacteria. Gene engineering of lantibiotics cannot obtain highly active mature lantibiotics from single expressing of lantibiotics structural gene. This study reviewed the mutation of orientation site of lantibiotics precursor molecule, after that, the secretory and non-secretory variant molecules which could produce structural variation were re-identified and modified by the modified enzymes. The mutation sites of lantibiotic molecular were classified and summarized, and the relationship between the molecular mutation sites and biological activity of lantibiotics was summarized. It might have important significance for the engineering modification and enhancing antibacterial activity of lantibiotic under the condition of limited application of existing lantibiotics.
Lantibiotics is a kind of antimicrobial peptides synthesized on bacterial ribosome and modified by post-translation processing, have been found in a variety of G+bacteria, most of which have inhibitory effects on G+bacteria. Gene engineering of lantibiotics cannot obtain highly active mature lantibiotics from single expressing of lantibiotics structural gene. This study reviewed the mutation of orientation site of lantibiotics precursor molecule, after that, the secretory and non-secretory variant molecules which could produce structural variation were re-identified and modified by the modified enzymes. The mutation sites of lantibiotic molecular were classified and summarized, and the relationship between the molecular mutation sites and biological activity of lantibiotics was summarized. It might have important significance for the engineering modification and enhancing antibacterial activity of lantibiotic under the condition of limited application of existing lantibiotics.
引文
Allgaier H.,Jung G.,Werner R.G.,Schneider U.,and Z覿hner H.,1986,Epidermin:sequencing of a heterodet tetracyclic21-peptide amide antibiotic,Eur.J.Biochem.,160(1):9-22
Altena K.,Guder A.,Cramer C.,and Bierbaum G.,2000,Biosynthesis of the lantibiotic mersacidin:organization of a type Blantibiotic gene cluster,Appl.Environ.Microbiol.,66(6):2565-2571
Bierbaum G.,Reis M.,Szekat C.,and Sahl H.G.,1994,Construction of an expression system for engineering of the lantibiotic Pep5,Appl.Environ.Microbiol.,60(12):4332-4338
Caetano T.,Barbosa J.,Moesker E.,Süssmuth R.D.,and Mendo S.,2014,Bioengineering of lanthipeptides in Escherichia coli:assessing the specificity of lichenicidin and haloduracin biosynthetic machinery,Res.Microbiol.,165(7):600-604
Chatterjee S.,Chatterjee S.,Lad S.J.,Phansalkar M.S.,Rupp R.H.,Ganguli B.N.,Fehlhaber H.W.,and Kogler H.,1992,Mersacidin,a new antibiotic from Bacillus.Fermentation,isolation,purification and chemical characterization,J.Antibiot.,45(6):832-838
Chen P.,Novak J.,Kirk M.,Barnes S.,Qi F.,and Caufield P.W.,1998,Structure-activity study of the lantibiotic mutacinⅡfrom Streptococcus mutans T8 by a gene replacement strategy,Appl.Environ.Microbiol.,64(7):2335-2340
Cotter P.D.,O'Connor P.M.,Draper L.A.,Lawton E.M.,Deegan L.H.,Hill C.,and Ross R.P.,2005,Posttranslational conversion of L-serines to D-alanines is vital for optimal production and activity of the lantibiotic lacticin 3147,Proc.Natl.Acad.Sci.USA,102(51):18584-18589
De Kwaadsteniet M.,Ten Doeschate K.,and Dicks L.M.,2008,Characterization of the structural gene encoding nisin F,a new lantibiotic produced by Lactococcus lactis subsp lactis isolated from fresh water catfish(Clarias gariepinus),Appl.Environ.Microbiol.,74(2):547-549
Engelke G.,Gutowski-Eckel Z.,Kiesau P.,Siegers K.,Hammelmann M.,and Entian K.D.,1994,Regulation of nisin biosynthesis and immunity in Lactococcus lactis 6F3,Appl.Environ.Microbiol.,60(3):814-825
Field D.,Cotter P.D.,Ross R.P.,and Hill C.,2015,Bioengineering of the model lantibiotic nisin,Bioengineered,6(4):187-192
Field D.,O'Connor P.M.,Cotter P.D.,Hill C.,and Ross R.P.,2008,The generation of nisin variants with enhanced activity against specific gram-positive pathogens,Mol.Microbiol.,69(1):218-230
Field D.,Quigley L.,O'Connor P.M.,Rea M.C.,Daly K.,Cotter P.D.,Hill C.,and Ross R.P.,2010,Studies with bioengineered Nisin peptides highlight the broad-spectrum potency of Nisin V,Microb.Biotechnol.,3(4):473-486
Floss H.G.,2006,Combinatorial biosynthesis-potential and problems,J.Biotechnol.,124(1):242-257
Fuchs S.W.,Jaskolla T.W.,Bochmann S.,Kotter P.,Wichelhaus T.,Karas M.,Stein T.,and Entian K.D.,2011,Entianin,a novel subtilin-like lantibiotic from Bacillus subtilis subsp.spizizenii DSM 15029T with high antimicrobial activity,Appl.Environ.Microbiol.,77(5):1698-1707
Gong T.,Xu X.,Che Y.,Liu R.,Gao W.,Zhao F.,Yu H.,Liang J.,Xu P.,Song C.,and Yang C.,2017,Combinatorial metabolic engineering of Pseudomonas putida KT2440 for efficient mineralization of 1,2,3-trichloropropane,Sci.Rep.,7(1):7064
Goto Y.,Li B.,Claesen J.,Shi Y.,Bibb M.J.,and van der Donk W.A.,2010,Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights,PLoS Biol.,8(3):1000339
Healy B.,Field D.,O'Connor P.M.,Hill C.,Cotter P.D.,and Ross R.P.,2013,Intensive mutagenesis of the nisin hinge leads to the rational design of enhanced derivatives,PLoS One,8(11):79563
Kaletta C.,and Entian K.D.,1989,Nisin,a peptide antibiotic:cloning and sequencing of the nis A gene and posttranslational processing of its peptide product,J.Bacteriol.,171(3):1597-1601
Kellner R.,Jung G.,Horner T.,Zhner H.,Schnell N.,Entian K.D.,and Gotz F.,1988,Gallidermin:a new lanthionine-containing polypeptide antibiotic,Eur.J.Biochem.,177(1):53-59
Kim B.,Du J.,Eriksen D.T.,and Zhao H.,2013,Combinatorial design of a highly efficient xylose-utilizing pathway in Saccharomyces cerevisiae for the production of cellulosic biofuels,Appl.Environ.Microbiol.,79(3):931-941
Klaenhammer T.R.,1993,Genetics of bacteriocins produced by lactic acid bacteria,FEMS Microbiol.Rev.,12(1-3):39-86
Knerr P.J.,and van der Donk W.A.,2012,Discovery,biosynthesis,and engineering of lantipeptides,Annu.Rev.Biochem.,81(1):479-505
Kodani S.,Hudson M.E.,Durrant M.C.,Buttner M.J.,Nodwell J.R.,and Willey J.M.,2004,The SapB morphogen is a lantibiotic-like peptide derived from the product of the developmental gene ramS in Streptomyces coelicolor,Proc.Natl.Acad.Sci.USA,101(31):11448-11453
Kong Z.,and Zhao D.,2008,The combination of CHI and AFPgenes introduced into ryegrass mediated by Agrobacterium,Fenzi Zhiwu Yuzhong(Molecular Plant Breeding),6(2):281-285(孔政,赵德刚,2008,苦瓜几丁质酶基因-益母草抗菌肽基因遗传转化黑麦草,分子植物育种,6(2):281-285)
Kupke T.,and Gotz F.,2006,In vivo reaction of affinity-taglabelled epidermin precursor peptide with flavoenzyme EpiD,FEMS Microbiol.Lett.,153(1):25-32
Li Y.,Yu X.,Li N.,Wang H.,and Huang Z.,2005,Evaluation of resistance to bacterial wilt and systemic breeding in cecropin-gm Capsicum,Fenzi Zhiwu Yuzhong(Molecular Plant Breeding),3(2):217-221(李颖,余小林,李乃坚,王恒明,黄自然,2005,转抗菌肽基因辣椒株系的青枯病抗性鉴定及系统选育,分子植物育种,3(2):217-221)
Liu W.,and Hansen J.N.,1992,Enhancement of the chemical and antimicrobial properties of subtilin by site-directed mutagenesis,J.Biol.Chem.,267(35):25078-25085
Liu W.,and Hansen J.N.,1993,The antimicrobial effect of a structural variant of subtilin against outgrowing Bacillus cereus T spores and vegetative cells occurs by different mechanisms,Appl.Environ.Microbiol.,59(2):648-651
Molloy E.M.,Field D.,O'Connor P.M.,Cotter P.D.,Hill C.,and Ross R.P.,2013,Saturation mutagenesis of lysine 12 leads to the identification of derivatives of nisin A with enhanced antimicrobial activity,PLo S One,8(3):58530
Mulders J.W.M.,Boerrigter I.J.,Rollema H.S.,Siezen R.J.,and de Vos W.M.,1991,Identification and characterization of the lantibiotic nisin Z,a natural nisin variant,Eur.J.Biochem.,201(3):581-584
Müller W.M.,Schmiederer T.,Ensle P.,and Süssmuth R.D.,2010,In vitro biosynthesis of the prepeptide of type-Ⅲlantibiotic labyrinthopeptin A2 including formation of a C-Cbond as a post-translational modification,Angew.Chem.Int.Ed.,49(13):2436-2440
Ottenwlder B.,Kupke T.,Brecht S.,Gnau V.,Metzger J.,Jung G.,and Gotz F.,1995,Isolation and characterization of genetically engineered gallidermin and epidermin analogs,Appl.Environ.Microbiol.,61(11):3894-3903
Pag U.,and Sahl H.G.,2002,Multiple activities in lantibiotics-models for the design of novel antibiotics?Curr.Pharm.Des.,8(9):815-833
RincéA.,Dufour A.,Uguen P.,Le Pennec J.P.,and Haras D.,1997,Characterization of the lacticin 481 operon:the Lactococcus lactis genes lctF,lctE,and lctG encode a putative ABC transporter involved in bacteriocin immunity,Appl.Environ.Microbiol.,63(11):4252-4260
Sahl H.G.,and Brandis H.,1981,Production,purification and chemical properties of an antistaphylococcal agent produced by Staphylococcus epidermidis,J.Gen.Microbiol.,127(2):377-384
Siegers K.,and Entian K.D.,1995,Genes involved in immunity to the lantibiotic nisin produced by Lactococcus lactis 6F3,Appl.Environ.Microbiol.,61(3):1082-1089
SpieβT.,Korn S.M.,Kotter P.,and Entian K.D.,2015,Activation of histidine kinase SpaK is mediated by the n-terminal portion of subtilin-like lantibiotics and is independent of LipidⅡ,Appl.Environ.Microbiol.,81(16):5335-5343
Stein T.,Borchert S.,Conrad B.,Feesche J.,Hofemeister B.,Hofemeister J.,and Entian K.D.,2002,Two different lantibiotic-like peptides originate from the ericin gene cluster of Bacillus subtilis A1/3,J.Bacteriol.,184(6):1703-1711
Szekat C.,Jack R.W.,Skutlarek D.,Frber H.,and Bierbaum G.,2003,Construction of an expression system for site-directed mutagenesis of the lantibiotic mersacidin,Appl.Environ.Microbiol.,69(7):3777-3783
Van der Donk W.A.,and Nair S.K.,2014,Structure and mechanism of lanthipeptide biosynthetic enzymes,Curr.Opin.Struct.Biol.,29:58-66
Van Heel A.J.,Mu D.,Montalbán-López M.,Hendriks D.,and Kuipers O.P.,2013,Designing and producing modified,new-to-nature peptides with antimicrobial activity by use of a combination of various lantibiotic modification enzymes,ACS.Synth.Biol.,2(7):397-404
Wirawan R.E.,Klesse N.A.,Jack R.W.,and Tagg J.R.,2006,Molecular and genetic characterization of a novel nisin variant produced by Streptococcus uberis,Appl.Environ.Microbiol.,72(2):1148-1156
Xie L.,Miller L.M.,Chatterjee C.,Averin O.,Kelleher N.L.,and van der Donk W.A.,2004,Lacticin 481:in vitro reconstitution of lantibiotic synthetase activity,Science,303(5658):679-681
Yang X.,and van der Donk W.H,2013,Ribosomally synthesized and post-translationally modified peptide natural products:new insights into the role of leader and core peptides during biosynthesis,Chemistry,19(24):7662-7677
Yu Y.,Zhang Q.,and van der Donk W.A.,2013,Insights into the evolution of lanthipeptide biosynthesis,Protein Sci.,22(11):1478-1489
Yuan J.,Zhang Z.Z.,Chen X.Z.,Yang W.,and Huan L.D.,2004,Site directed mutagenesis of the hinge region of nisinZ and properties of nisinZ mutants,Appl.Microbiol.Biotechnol.,64(6):806-815
Zendo T.,Fukao M.,Ueda K.,Higuchi T.,Nakayama J.,and Sonomoto K.,2003,Identification of the lantibiotic nisin Q,a new natural nisin variant produced by Lactococcus lactis61-14 isolated from a river in Japan,Biosci.Biotechnol.Biochem.,67(7):1616-1619
Zhang Q.,Yu Y.,Vélasquez J.E.,and van der Donk W.A.,2012,Evolution of lanthipeptide synthetases,Proc.Natl.Acad.Sci.USA,109(45):18361-18366
Zhou L.,van Heel A.L.,and Kuipers O.P.,2015,The length of a lantibiotic hinge region has profound influence on antimicrobial activity and host specificity,Front.Microbiol.,6(11):39-58
Altena K.,Guder A.,Cramer C.,and Bierbaum G.,2000,Biosynthesis of the lantibiotic mersacidin:organization of a type Blantibiotic gene cluster,Appl.Environ.Microbiol.,66(6):2565-2571
Bierbaum G.,Reis M.,Szekat C.,and Sahl H.G.,1994,Construction of an expression system for engineering of the lantibiotic Pep5,Appl.Environ.Microbiol.,60(12):4332-4338
Caetano T.,Barbosa J.,Moesker E.,Süssmuth R.D.,and Mendo S.,2014,Bioengineering of lanthipeptides in Escherichia coli:assessing the specificity of lichenicidin and haloduracin biosynthetic machinery,Res.Microbiol.,165(7):600-604
Chatterjee S.,Chatterjee S.,Lad S.J.,Phansalkar M.S.,Rupp R.H.,Ganguli B.N.,Fehlhaber H.W.,and Kogler H.,1992,Mersacidin,a new antibiotic from Bacillus.Fermentation,isolation,purification and chemical characterization,J.Antibiot.,45(6):832-838
Chen P.,Novak J.,Kirk M.,Barnes S.,Qi F.,and Caufield P.W.,1998,Structure-activity study of the lantibiotic mutacinⅡfrom Streptococcus mutans T8 by a gene replacement strategy,Appl.Environ.Microbiol.,64(7):2335-2340
Cotter P.D.,O'Connor P.M.,Draper L.A.,Lawton E.M.,Deegan L.H.,Hill C.,and Ross R.P.,2005,Posttranslational conversion of L-serines to D-alanines is vital for optimal production and activity of the lantibiotic lacticin 3147,Proc.Natl.Acad.Sci.USA,102(51):18584-18589
De Kwaadsteniet M.,Ten Doeschate K.,and Dicks L.M.,2008,Characterization of the structural gene encoding nisin F,a new lantibiotic produced by Lactococcus lactis subsp lactis isolated from fresh water catfish(Clarias gariepinus),Appl.Environ.Microbiol.,74(2):547-549
Engelke G.,Gutowski-Eckel Z.,Kiesau P.,Siegers K.,Hammelmann M.,and Entian K.D.,1994,Regulation of nisin biosynthesis and immunity in Lactococcus lactis 6F3,Appl.Environ.Microbiol.,60(3):814-825
Field D.,Cotter P.D.,Ross R.P.,and Hill C.,2015,Bioengineering of the model lantibiotic nisin,Bioengineered,6(4):187-192
Field D.,O'Connor P.M.,Cotter P.D.,Hill C.,and Ross R.P.,2008,The generation of nisin variants with enhanced activity against specific gram-positive pathogens,Mol.Microbiol.,69(1):218-230
Field D.,Quigley L.,O'Connor P.M.,Rea M.C.,Daly K.,Cotter P.D.,Hill C.,and Ross R.P.,2010,Studies with bioengineered Nisin peptides highlight the broad-spectrum potency of Nisin V,Microb.Biotechnol.,3(4):473-486
Floss H.G.,2006,Combinatorial biosynthesis-potential and problems,J.Biotechnol.,124(1):242-257
Fuchs S.W.,Jaskolla T.W.,Bochmann S.,Kotter P.,Wichelhaus T.,Karas M.,Stein T.,and Entian K.D.,2011,Entianin,a novel subtilin-like lantibiotic from Bacillus subtilis subsp.spizizenii DSM 15029T with high antimicrobial activity,Appl.Environ.Microbiol.,77(5):1698-1707
Gong T.,Xu X.,Che Y.,Liu R.,Gao W.,Zhao F.,Yu H.,Liang J.,Xu P.,Song C.,and Yang C.,2017,Combinatorial metabolic engineering of Pseudomonas putida KT2440 for efficient mineralization of 1,2,3-trichloropropane,Sci.Rep.,7(1):7064
Goto Y.,Li B.,Claesen J.,Shi Y.,Bibb M.J.,and van der Donk W.A.,2010,Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights,PLoS Biol.,8(3):1000339
Healy B.,Field D.,O'Connor P.M.,Hill C.,Cotter P.D.,and Ross R.P.,2013,Intensive mutagenesis of the nisin hinge leads to the rational design of enhanced derivatives,PLoS One,8(11):79563
Kaletta C.,and Entian K.D.,1989,Nisin,a peptide antibiotic:cloning and sequencing of the nis A gene and posttranslational processing of its peptide product,J.Bacteriol.,171(3):1597-1601
Kellner R.,Jung G.,Horner T.,Zhner H.,Schnell N.,Entian K.D.,and Gotz F.,1988,Gallidermin:a new lanthionine-containing polypeptide antibiotic,Eur.J.Biochem.,177(1):53-59
Kim B.,Du J.,Eriksen D.T.,and Zhao H.,2013,Combinatorial design of a highly efficient xylose-utilizing pathway in Saccharomyces cerevisiae for the production of cellulosic biofuels,Appl.Environ.Microbiol.,79(3):931-941
Klaenhammer T.R.,1993,Genetics of bacteriocins produced by lactic acid bacteria,FEMS Microbiol.Rev.,12(1-3):39-86
Knerr P.J.,and van der Donk W.A.,2012,Discovery,biosynthesis,and engineering of lantipeptides,Annu.Rev.Biochem.,81(1):479-505
Kodani S.,Hudson M.E.,Durrant M.C.,Buttner M.J.,Nodwell J.R.,and Willey J.M.,2004,The SapB morphogen is a lantibiotic-like peptide derived from the product of the developmental gene ramS in Streptomyces coelicolor,Proc.Natl.Acad.Sci.USA,101(31):11448-11453
Kong Z.,and Zhao D.,2008,The combination of CHI and AFPgenes introduced into ryegrass mediated by Agrobacterium,Fenzi Zhiwu Yuzhong(Molecular Plant Breeding),6(2):281-285(孔政,赵德刚,2008,苦瓜几丁质酶基因-益母草抗菌肽基因遗传转化黑麦草,分子植物育种,6(2):281-285)
Kupke T.,and Gotz F.,2006,In vivo reaction of affinity-taglabelled epidermin precursor peptide with flavoenzyme EpiD,FEMS Microbiol.Lett.,153(1):25-32
Li Y.,Yu X.,Li N.,Wang H.,and Huang Z.,2005,Evaluation of resistance to bacterial wilt and systemic breeding in cecropin-gm Capsicum,Fenzi Zhiwu Yuzhong(Molecular Plant Breeding),3(2):217-221(李颖,余小林,李乃坚,王恒明,黄自然,2005,转抗菌肽基因辣椒株系的青枯病抗性鉴定及系统选育,分子植物育种,3(2):217-221)
Liu W.,and Hansen J.N.,1992,Enhancement of the chemical and antimicrobial properties of subtilin by site-directed mutagenesis,J.Biol.Chem.,267(35):25078-25085
Liu W.,and Hansen J.N.,1993,The antimicrobial effect of a structural variant of subtilin against outgrowing Bacillus cereus T spores and vegetative cells occurs by different mechanisms,Appl.Environ.Microbiol.,59(2):648-651
Molloy E.M.,Field D.,O'Connor P.M.,Cotter P.D.,Hill C.,and Ross R.P.,2013,Saturation mutagenesis of lysine 12 leads to the identification of derivatives of nisin A with enhanced antimicrobial activity,PLo S One,8(3):58530
Mulders J.W.M.,Boerrigter I.J.,Rollema H.S.,Siezen R.J.,and de Vos W.M.,1991,Identification and characterization of the lantibiotic nisin Z,a natural nisin variant,Eur.J.Biochem.,201(3):581-584
Müller W.M.,Schmiederer T.,Ensle P.,and Süssmuth R.D.,2010,In vitro biosynthesis of the prepeptide of type-Ⅲlantibiotic labyrinthopeptin A2 including formation of a C-Cbond as a post-translational modification,Angew.Chem.Int.Ed.,49(13):2436-2440
Ottenwlder B.,Kupke T.,Brecht S.,Gnau V.,Metzger J.,Jung G.,and Gotz F.,1995,Isolation and characterization of genetically engineered gallidermin and epidermin analogs,Appl.Environ.Microbiol.,61(11):3894-3903
Pag U.,and Sahl H.G.,2002,Multiple activities in lantibiotics-models for the design of novel antibiotics?Curr.Pharm.Des.,8(9):815-833
RincéA.,Dufour A.,Uguen P.,Le Pennec J.P.,and Haras D.,1997,Characterization of the lacticin 481 operon:the Lactococcus lactis genes lctF,lctE,and lctG encode a putative ABC transporter involved in bacteriocin immunity,Appl.Environ.Microbiol.,63(11):4252-4260
Sahl H.G.,and Brandis H.,1981,Production,purification and chemical properties of an antistaphylococcal agent produced by Staphylococcus epidermidis,J.Gen.Microbiol.,127(2):377-384
Siegers K.,and Entian K.D.,1995,Genes involved in immunity to the lantibiotic nisin produced by Lactococcus lactis 6F3,Appl.Environ.Microbiol.,61(3):1082-1089
SpieβT.,Korn S.M.,Kotter P.,and Entian K.D.,2015,Activation of histidine kinase SpaK is mediated by the n-terminal portion of subtilin-like lantibiotics and is independent of LipidⅡ,Appl.Environ.Microbiol.,81(16):5335-5343
Stein T.,Borchert S.,Conrad B.,Feesche J.,Hofemeister B.,Hofemeister J.,and Entian K.D.,2002,Two different lantibiotic-like peptides originate from the ericin gene cluster of Bacillus subtilis A1/3,J.Bacteriol.,184(6):1703-1711
Szekat C.,Jack R.W.,Skutlarek D.,Frber H.,and Bierbaum G.,2003,Construction of an expression system for site-directed mutagenesis of the lantibiotic mersacidin,Appl.Environ.Microbiol.,69(7):3777-3783
Van der Donk W.A.,and Nair S.K.,2014,Structure and mechanism of lanthipeptide biosynthetic enzymes,Curr.Opin.Struct.Biol.,29:58-66
Van Heel A.J.,Mu D.,Montalbán-López M.,Hendriks D.,and Kuipers O.P.,2013,Designing and producing modified,new-to-nature peptides with antimicrobial activity by use of a combination of various lantibiotic modification enzymes,ACS.Synth.Biol.,2(7):397-404
Wirawan R.E.,Klesse N.A.,Jack R.W.,and Tagg J.R.,2006,Molecular and genetic characterization of a novel nisin variant produced by Streptococcus uberis,Appl.Environ.Microbiol.,72(2):1148-1156
Xie L.,Miller L.M.,Chatterjee C.,Averin O.,Kelleher N.L.,and van der Donk W.A.,2004,Lacticin 481:in vitro reconstitution of lantibiotic synthetase activity,Science,303(5658):679-681
Yang X.,and van der Donk W.H,2013,Ribosomally synthesized and post-translationally modified peptide natural products:new insights into the role of leader and core peptides during biosynthesis,Chemistry,19(24):7662-7677
Yu Y.,Zhang Q.,and van der Donk W.A.,2013,Insights into the evolution of lanthipeptide biosynthesis,Protein Sci.,22(11):1478-1489
Yuan J.,Zhang Z.Z.,Chen X.Z.,Yang W.,and Huan L.D.,2004,Site directed mutagenesis of the hinge region of nisinZ and properties of nisinZ mutants,Appl.Microbiol.Biotechnol.,64(6):806-815
Zendo T.,Fukao M.,Ueda K.,Higuchi T.,Nakayama J.,and Sonomoto K.,2003,Identification of the lantibiotic nisin Q,a new natural nisin variant produced by Lactococcus lactis61-14 isolated from a river in Japan,Biosci.Biotechnol.Biochem.,67(7):1616-1619
Zhang Q.,Yu Y.,Vélasquez J.E.,and van der Donk W.A.,2012,Evolution of lanthipeptide synthetases,Proc.Natl.Acad.Sci.USA,109(45):18361-18366
Zhou L.,van Heel A.L.,and Kuipers O.P.,2015,The length of a lantibiotic hinge region has profound influence on antimicrobial activity and host specificity,Front.Microbiol.,6(11):39-58