Skip to main content
SpringerLink
Log in

Contribution of the Actinobacteria to the growing diversity of lantibiotics

  • Review
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

Currently, 76 lantibiotics have been described; the vast majority being produced by members of the Firmicute phylum of bacteria. There is a growing number being identified from the Actinobacteria phylum and some of these exhibit novel modifications leading to an increased functional diversity among lantibiotics. In this review, we discuss the currently characterized lantibiotics highlighting the expanding diversity provided by those from the Actinobacteria. This increased diversity has the potential to expand lantibiotic applications as antimicrobials in foods and pharmaceuticals. In addition, a phylogenetic classification system based on the full prepropeptide sequences showed remarkable consistency with current classification systems and may provide a more rapid and convenient means for classifying lantibiotics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Asaduzzaman SM, J-i Nagao, Iida H, Zendo T, Nakayama J, Sonomoto K (2009) Nukacin ISK-1, a bacteriostatic lantibiotic. Antimicrob Agents Chemother 53:3595–3598

    Article  PubMed  CAS  Google Scholar 

  • Bonelli RR, Schneider T, Sahl HG, Wiedemann I (2006) Insights into in vivo activities of lantibiotics from gallidermin and epidermin mode-of-action studies. Antimicrob Agents Chemother 50:1449–1457

    Article  PubMed  CAS  Google Scholar 

  • Breukink E, Wiedemann I, van Kraaij C, Kuipers OP, Sahl HG, de Kruijff B (1999) Use of the cell wall precursor lipid II by a pore-forming peptide antibiotic. Science 286:2361–2364

    Article  PubMed  CAS  Google Scholar 

  • Brotz H, Bierbaum G, Reynolds PE, Sahl HG (1997) The lantibiotic mersacidin inhibits peptidoglycan biosynthesis at the level of transglycosylation. Eur J Biochem 246:193–199

    Article  PubMed  CAS  Google Scholar 

  • Brotz H, Bierbaum G, Leopold K, Reynolds PE, Sahl HG (1998a) The lantibiotic mersacidin inhibits peptidoglycan synthesis by targeting lipid II. Antimicrob Agents Chemother 42:154–160

    PubMed  CAS  Google Scholar 

  • Brotz H, Josten M, Wiedemann I, Schneider U, Gotz F, Bierbaum G, Sahl HG (1998b) Role of lipid-bound peptidoglycan precursors in the formation of pores by nisin, epidermin and other lantibiotics. Mol Microbiol 30:317–327

    Article  PubMed  CAS  Google Scholar 

  • Burton JP, Chilcott CN, Moore CJ, Speiser G, Tagg JR (2006) A preliminary study of the effect of probiotic Streptococcus salivarius K12 on oral malodour parameters. J Appl Microbiol 100:754–764

    Article  PubMed  CAS  Google Scholar 

  • Castiglione F, Cavaletti L, Losi D, Lazzarini A, Carrano L, Feroggio M, Ciciliato I, Corti E, Candiani G, Marinelli F, Selva E (2007) A novel lantibiotic acting on bacterial cell wall synthesis produced by the uncommon actinomycete Planomonospora sp. Biochemistry 46:5884–5895

    Article  PubMed  CAS  Google Scholar 

  • Castiglione F, Lazzarini A, Carrano L, Corti E, Ciciliato I, Gastaldo L, Candiani P, Losi D, Marinelli F, Selva E, Parenti F (2008) Determining the structure and mode of action of microbisporicin, a potent lantibiotic active against multiresistant pathogens. Chem Biol 15:22–31

    Article  PubMed  CAS  Google Scholar 

  • Chandrapati S, O’Sullivan DJ (1999) Nisin independent induction of the nisA promoter in Lactococcus lactis during growth in lactose or galactose. FEMS Microbiol Lett 170:191–198

    PubMed  CAS  Google Scholar 

  • Chandrapati S, O’Sullivan DJ (2002) Characterization of the promoter regions involved in galactose- and nisin-mediated induction of the nisA gene in Lactococcus lactis ATCC 11454. Mol Microbiol 46:467–477

    Article  PubMed  CAS  Google Scholar 

  • Chatterjee C, Paul M, Xie LL, van der Donk WA (2005) Biosynthesis and mode of action of lantibiotics. Chem Rev 105:633–683

    Article  PubMed  CAS  Google Scholar 

  • Chen P, Qi FX, Novak J, Caufield PW (1999) The specific genes for lantibiotic mutacin II biosynthesis in Streptococcus mutans T8 are clustered and can be transferred en bloc. Appl Environ Microbiol 65:1356–1360

    PubMed  CAS  Google Scholar 

  • Choung SY, Kobayashi T, Inoue J, Takemoto K, Ishitsuka H, Inoue K (1988) Hemolytic activity of a cyclic peptide Ro09-0198 isolated from Streptoverticillium. Biochim Biophys Acta 940:171–179

    Article  PubMed  CAS  Google Scholar 

  • Devos WM, Kuipers OP, Vandermeer JR, Siezen RJ (1995) Maturation pathway of nisin and other lantibiotics-post-translationally modified antimicrobial peptides exported by Gram-positive bacteria. Mol Microbiol 17:427–437

    Article  CAS  Google Scholar 

  • Fernandez L, Delgado S, Herrero H, Maldonado A, Rodriguez JM (2008) The bacteriocin nisin, an effective agent for the treatment of staphylococcal mastitis during lactation. J Hum Lact 24:311–316

    Article  PubMed  Google Scholar 

  • Foulston L, Bibb M (2011) Feed-forward regulation of microbisporicin biosynthesis in Microbispora corallina. J Bacteriol 193:3064–3071

    Article  PubMed  CAS  Google Scholar 

  • Gomez A, Ladire M, Marcille F, Fons M (2002) Trypsin mediates growth phase-dependent transcriptional regulation of genes involved in biosynthesis of ruminococcin A, a lantibiotic produced by a Ruminococcus gnavus strain from a human intestinal microbiota. J Bacteriol 184:18–28

    Article  PubMed  CAS  Google Scholar 

  • Gross E, Morell JL (1971) The structure of nisin. J Am Chem Soc 93:4634–4635

    Article  PubMed  CAS  Google Scholar 

  • Guder A, Schmitter T, Wiedemann I, Sahl HG, Bierbaum G (2002) Role of the single regulator MrsR1 and the two-component system MrsR2/K2 in the regulation of mersacidin production and immunity. Appl Environ Microbiol 68:106–113

    Article  PubMed  CAS  Google Scholar 

  • Gut IM, Blanke SR, van der Donk WA (2011) Mechanism of Inhibition of Bacillus anthracis spore outgrowth by the lantibiotic nisin. ACS Chem Biol 6:744–752

    Article  PubMed  CAS  Google Scholar 

  • Hasper HE, de Kruijff B, Breukink E (2004) Assembly and stability of nisin-Lipid II pores. Biochemistry 43:11567–11575

    Article  PubMed  CAS  Google Scholar 

  • Hasper HE, Kramer NE, Smith JL, Hillman JD, Zachariah C, Kuipers OP, de Kruijff B, Breukink E (2006) An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II. Science 313:1636–1637

    Article  PubMed  CAS  Google Scholar 

  • Havarstein LS, Diep DB, Nes IF (1995) A family of bacteriocin ABC transporters carry out proteolytic processing of their substrates concomitant with export. Mol Microbiol 16:229–240

    Article  PubMed  CAS  Google Scholar 

  • Hsu STD, Breukink E, Tischenko E, Lutters MAG, de Kruijff B, Kaptein R, Bonvin A, van Nuland NAJ (2004) The nisin-lipid II complex reveals a pyrophosphate cage that provides a blueprint for novel antibiotics. Nat Struct Mol Biol 11:963–967

    Article  PubMed  CAS  Google Scholar 

  • Islam MR, Nishie M, J-i Nagao, Zendo T, Keller S, Nakayama J, Kohda D, Sahl H-G, Sonomoto K (2012) Ring A of nukacin ISK-1: a lipid II-binding motif for type-A(II) lantibiotic. J Am Chem Soc 134:3687–3690

    Article  PubMed  CAS  Google Scholar 

  • Iwamoto K, Hayakawa T, Murate M, Makino A, Ito K, Fujisawa T, Kobayashi T (2007) Curvature-dependent recognition of ethanolamine phospholipids by duramycin and cinnamycin. Biophys J 93:1608–1619

    Article  PubMed  CAS  Google Scholar 

  • Jack R, Benz R, Tagg J, Sahl HG (1994) The mode of action of SA-FF22, a lantibiotic isolated from Streptococcus pyogenes strain FF22. Eur J Biochem 219:699–705

    Article  PubMed  CAS  Google Scholar 

  • Jung G (1991) Lantibiotics-ribosomally synthesized biologically-active polypeptides containing sulfide bridges and alpha-beta-didehydroamino acids. Angew Chem Int Ed 30:1051–1068

    Article  Google Scholar 

  • Kido Y, Hamakado T, Yoshida T, Anno M, Motoki Y, Wakamiya T, Shiba T (1983) Isolation and characterization of ancovenin, a new inhibitor of angiotensin-I converting enzyme, produced by actinomycetes. J Antibiot 36:1295–1299

    Article  PubMed  CAS  Google Scholar 

  • Kies S, Vuong C, Hille M, Peschel A, Meyer C, Gotz F, Otto M (2003) Control of antimicrobial peptide synthesis by the agr quorum sensing system in Staphylococcus epidermidis: activity of the lantibiotic epidermin is regulated at the level of precursor peptide processing. Peptides 24:329–338

    Article  PubMed  CAS  Google Scholar 

  • Klostermann K, Crispie F, Flynn J, Meaney WJ, Ross RP, Hill C (2010) Efficacy of a teat dip containing the bacteriocin lacticin 3147 to eliminate Gram-positive pathogens associated with bovine mastitis. J Dairy Res 77:231–238

    Article  PubMed  CAS  Google Scholar 

  • Koponen O, Tolonen M, Qiao MQ, Wahlstrom G, Helin J, Saris PEJ (2002) NisB is required for the dehydration and NisC for the lanthionine formation in the post-translational modification of nisin. Microbiology 148:3561–3568

    PubMed  CAS  Google Scholar 

  • Kordel M, Benz R, Sahl HG (1988) Mode of action of the staphylococcin-like peptide pep5-voltage dependent depolarization of bacterial and artificial membranes. J Bacteriol 170:84–88

    PubMed  CAS  Google Scholar 

  • Kruszewska D, Sahl HG, Bierbaum G, Pag U, Hynes SO, Ljungh A (2004) Mersacidin eradicates methicillin-resistant Staphylococcus aureus (MRSA) in a mouse rhinitis model. J Antimicrob Chemother 54:648–653

    Article  PubMed  CAS  Google Scholar 

  • Kuipers OP, Beerthuyzen MM, Siezen RJ, Devos WM (1993) Characterization of the nisin gene cluster nisABTCIPR of Lactococcus lactis requirement of expression of the nisA and nisI genes for development of immunity. Eur J Biochem 216:281–291

    Article  PubMed  CAS  Google Scholar 

  • Kuipers OP, Beerthuyzen MM, Deruyter P, Luesink EJ, Devos WM (1995) Autoregulation of nisin biosynthesis in Lactococcus lactis by signal transduction. J Biol Chem 270:27299–27304

    Article  PubMed  CAS  Google Scholar 

  • Kupke T, Stevanovic S, Sahl HG, Gotz F (1992) Purification and characterization of EpiD, a flavoprotein involved in the biosynthesis of the lantibiotic epidermin. J Bacteriol 174:5354–5361

    PubMed  CAS  Google Scholar 

  • Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) Clustal W and clustal X version 2.0. Bioinformatics 23:2947–2948

    Article  PubMed  CAS  Google Scholar 

  • Lee J-H, Li X, O’Sullivan DJ (2011) Transcription analysis of a lantibiotic gene cluster from Bifidobacterium longum DJO10A. Appl Environ Microbiol 77:5879–5887

    Article  PubMed  CAS  Google Scholar 

  • Manosroi A, Khanrin P, Lohcharoenkal W, Werner RG, Gotz F, Manosroi W, Manosroi J (2010) Transdermal absorption enhancement through rat skin of gallidermin loaded in niosomes. Int J Pharm 392:304–310

    Article  PubMed  CAS  Google Scholar 

  • Marki F, Hanni E, Fredenhagen A, Vanoostrum J (1991) Mode of action of the lanthionine containing antibiotics duramycin, duramycin B and duramycin C, and cinnamycin as indirect inhibitors of phospholipase A2. Biochem Pharmacol 42:2027–2035

    Article  PubMed  CAS  Google Scholar 

  • McAuliffe O, Hill C, Ross RP (1999) Inhibition of Listeria monocytogenes in cottage cheese manufactured with a lacticin 3147-producing starter culture. J Appl Microbiol 86:251–256

    Article  PubMed  CAS  Google Scholar 

  • Meyer C, Bierbaum G, Heidrich C, Reis M, Suling J, Iglesiaswind MI, Kempter C, Molitor E, Sahl HG (1995) Nucleotide sequence of the lantibiotic pep5 biosynthesis gene cluster and functional analysis of pepP and pepC-evidence for a role of pepC in thioether formation. Eur J Biochem 232:478–489

    Article  PubMed  CAS  Google Scholar 

  • O’Sullivan DJ, Lee J-H (2011) Lantibiotics and uses thereof. US Patent No: 7,960,505

  • Oman TJ, van der Donk WA (2009) Insights into the mode of action of the two-peptide lantibiotic haloduracin. ACS Chem Biol 4:865–874

    Article  PubMed  CAS  Google Scholar 

  • Oman TJ, Lupoli TJ, Wang T-SA, Kahne D, Walker S, van der Donk WA (2011) Haloduracin alpha binds the peptidoglycan precursor lipid II with 2:1 stoichiometry. J Am Chem Soc 133:17544–17547

    Article  PubMed  CAS  Google Scholar 

  • Paolo SS, Huang J, Cohen SN, Thompson CJ (2006) rag genes: novel components of the RamR regulon that trigger morphological differentiation in Streptomyces coelicolor. Mol Microbiol 61:1167–1186

    Article  Google Scholar 

  • Patton GC, Paul M, Cooper LE, Chatterjee C, van der Donk WA (2008) The importance of the leader sequence for directing lanthionine formation in lacticin 481. Biochemistry 47:7342–7351

    Article  PubMed  CAS  Google Scholar 

  • Peschel A, Schnell N, Hille M, Entian KD, Gotz F (1997) Secretion of the lantibiotics epidermin and gallidermin: sequence analysis of the genes gdmT and gdmH, their influence on epidermin production and their regulation by EpiQ. Mol Gen Genet 254:312–318

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez E, Arques JL, Gaya P, Nunez M, Medina M (2001) Control of Listeria monocytogenes by bacteriocins and monitoring of bacteriocin-producing lactic acid bacteria by colony hybridization in semi-hard raw milk cheese. J Dairy Res 68:131–137

    Article  PubMed  CAS  Google Scholar 

  • Rogers LA, Whittier EO (1928) Limiting factors in the lactic fermentation. J Bacteriol 16:211–229

    PubMed  CAS  Google Scholar 

  • Sambeth GM, Sussmuth RD (2011) Synthetic studies toward labionin, a new alpha, alpha-disubstituted amino acid from type III lantibiotic labyrinthopeptin A2. J Pept Sci 17:581–584

    Article  PubMed  CAS  Google Scholar 

  • Schmitz S, Hoffmann A, Szekat C, Rudd B, Bierbaum G (2006) The lantibiotic mersacidin is an autoinducing peptide. Appl Environ Microbiol 72:7270–7277

    Article  PubMed  CAS  Google Scholar 

  • Schnell N, Entian KD, Schneider U, Gotz F, Zahner H, Kellner R, Jung G (1988) Prepeptide sequence of epidermin, a ribosomally synthesized antibiotic with 4 sulfide-rings. Nature 333:276–278

    Article  PubMed  CAS  Google Scholar 

  • Sen AK, Narbad A, Horn N, Dodd HM, Parr AJ, Colquhoun I, Gasson MJ (1999) Post-translational modification of nisin. The involvement of NisB in the dehydration process. Eur J Biochem 261:524–532

    Article  CAS  Google Scholar 

  • Siegers K, Entian KD (1995) Genes involved in immunity to the lantibiotic nisin produced by Lactococcus lactis 6F3. Appl Environ Microbiol 61:1082–1089

    PubMed  CAS  Google Scholar 

  • Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li WZ, Lopez R, McWilliam H, Remmert M, Soding J, Thompson JD, Higgins DG (2011) Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 7:539

    Article  PubMed  Google Scholar 

  • Siezen RJ, Kuipers OP, deVos WM (1996) Comparison of lantibiotic gene clusters and encoded proteins. Antonie Van Leeuwenhoek 69:171–184

    Article  PubMed  CAS  Google Scholar 

  • Stock AM, Robinson VL, Goudreau PN (2000) Two-component signal transduction. Annu Rev Biochem 69:183–215

    Article  PubMed  CAS  Google Scholar 

  • Szekat C, Jack RW, Skutlarek D, Farber H, Bierbaum G (2003) Construction of an expression system for site-directed mutagenesis of the lantibiotic mersacidin. Appl Environ Microbiol 69:3777–3783

    Article  PubMed  CAS  Google Scholar 

  • Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731–2739

    Article  PubMed  CAS  Google Scholar 

  • van der Meer JR, Polman J, Beerthuyzen MM, Siezen RJ, Kuipers OP, Devos WM (1993) Characterization of the Lactococcus lactis nisn A operon genes nisP, encoding a subtilisin-like serine protease involved in precursor processing, and nisR, encoding a regulatory protein involved in nisin biosynthesis. J Bacteriol 175:2578–2588

    PubMed  Google Scholar 

  • van Heusden HE, de Kruijff B, Breukink E (2002) Lipid II induces a transmembrane orientation of the pore-forming peptide lantibiotic nisin. Biochemistry 41:12171–12178

    Article  PubMed  Google Scholar 

  • Widdick DA, Dodd HM, Barraille P, White J, Stein TH, Chater KF, Gasson MJ, Bibb MJ (2003) Cloning and engineering of the cinnamycin biosynthetic gene cluster from Streptomyces cinnamoneus cinnamoneus DSM 40005. Proc Natl Acad Sci USA 100:4316–4321

    Article  PubMed  CAS  Google Scholar 

  • Wiedemann I, Bottiger T, Bonelli RR, Wiese A, Hagge SO, Gutsmann T, Seydel U, Deegan L, Hill C, Ross P, Sahl HG (2006) The mode of action of the lantibiotic lacticin 3147—a complex mechanism involving specific interaction of two peptides and the cell wall precursor lipid II. Mol Microbiol 61:285–296

    Article  PubMed  CAS  Google Scholar 

  • Willey JM, van der Donk WA (2007) Lantibiotics: peptides of diverse structure and function. Annu Rev Microbiol 61:477–501

    Article  PubMed  CAS  Google Scholar 

  • Xie LL, Miller LM, Chatterjee C, Averin O, Kelleher NL, van der Donk WA (2004) Lacticin 481: in vitro reconstitution of lantibiotic synthetase activity. Science 303:679–681

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The Midwest Dairy Association (MDA) and Dairy Management Inc (DMI) are acknowledged for funding that contributed in part to this study.

Author information

Authors and Affiliations

  1. Department of Food Science and Nutrition, Microbial and Plant Genomics Institute, University of Minnesota, 1500 Gortner Avenue, St. Paul, MN, 55108, USA

    Xiulan Li & Daniel J. O’Sullivan

Authors
  1. Xiulan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel J. O’Sullivan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel J. O’Sullivan.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 96 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, X., O’Sullivan, D.J. Contribution of the Actinobacteria to the growing diversity of lantibiotics. Biotechnol Lett 34, 2133–2145 (2012). https://doi.org/10.1007/s10529-012-1024-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-012-1024-2

Keywords

Search

Navigation