Gallidermin: a new lanthionine‐containing polypeptide antibiotic

Kellner, Roland; Jung, Günther; Hörner, Thomas; Zähner, Hans; Schnell, Norbert; Entian, Karl‐Dieter; Götz, Friedrich

doi:10.1111/j.1432-1033.1988.tb14344.x-i2

Cited by 147 publications

(48 citation statements)

References 18 publications

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“…Gallidermin, a type-A lantibiotic produced by Staphylococcus gallinarum shows striking structural similarities to nisin in the N-terminal double ring system which had been identified as the binding motif for targeting the pyrophosphate moiety of lipid II [11]. In contrast to nisin, due to the short molecular length, gallidermin is hardly able to form pores in membranes via peptide-lipid II complexes.…”

Section: Introductionmentioning

confidence: 96%

Analysis of membrane interactions of antibiotic peptides using ITC and biosensor measurements

Al-Kaddah

Reder-Christ

Klocek

et al. 2010

Biophysical Chemistry

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT

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Section: Introductionmentioning

confidence: 96%

Analysis of membrane interactions of antibiotic peptides using ITC and biosensor measurements

Al-Kaddah

Reder-Christ

Klocek

et al. 2010

Biophysical Chemistry

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“…Structures of the lantibiotics that activate cpr transcription (34,(42)(43)(44)(45)(46)49). Lantibiotic motifs and residues are coded as follows: red, meso-lanthione (Lan); blue, (2S,3S,6R)-3-methyl-lanthione (MeLan); purple, (2S,8S)-lysinoalanine; Dha, 2,3-didehydroalanine; Dhb, (Z)-2,3-didehydrobutyrine; Asp-OH, erythro-3-hydroxy--aspartic acid.…”

Section: Figmentioning

confidence: 99%

The Clostridium difficile cpr Locus Is Regulated by a Noncontiguous Two-Component System in Response to Type A and B Lantibiotics

2013

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The intestinal pathogen Clostridium difficile is known to grow only within the intestines of mammals, yet little is known about how the bacterium subsists in this environment. In the intestine, C. difficile must contend with innate defenses within the host, such as cationic antimicrobial peptides (CAMPs) produced by the host and the indigenous microbiota. In this study, we investigated the mechanism of activation and regulation of the CprABC transporter system, which provides resistance to multiple CAMPs and shows homology to the immunity systems of bacterial antimicrobial peptide producers. The CprABC system proved to be controlled by a noncontiguous two-component system consisting of the CprK sensor kinase and an orphan response regulator (CD3320; CprR). The CprK-CprR regulators were shown to activate cprABCK transcription in a manner similar to that by lantibiotic regulatory systems. Unlike lantibiotic producer regulation, regulation by CprK-CprR was activated by multiple lantibiotics produced by diverse Gram-positive bacteria. We identified a motif within these lantibiotics that is likely required for activation of cpr. Based on the similarities between the Cpr system and lantibiotic systems, we propose that the CprABC transporter and its regulators are relatives of lantibiotic systems that evolved to recognize multiple substrates to defend against toxins made by the intestinal microbiota.

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“…However, additional studies are needed to verify this assumption. Experimental studies suggest that the leader peptide is important for interacting with the dehydratase LanB, the cyclase LanC, and the transporter Leader peptide sequence alignments of structurally related class I lantibiotics, i.e., nisin produced by Lactococcus lactis, subtilin produced by Bacillus subtilis, epidermin produced by Staphylococcus epidermidis, gallidermin produced by Staphylococcus gallinarum, Pep5 produced by Staphylococcus epidermidis, epilancin K7 produced by Staphylococcus epidermidis, mutacin Ny266 produced by S. mutans Ny266, mutacin III produced by S. mutans UA787, mutacin 1140 produced by S. mutans JH1140, and, for comparison, lacticin 481 (a class II lantibiotic) produced by Lactococcus lactis (16,18,(47)(48)(49)(50)(51)(52)(53). In the sequences, the F(N/D)LD box and C-terminal proline in class I lantibiotics are underlined and in bold, respectively.…”

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confidence: 99%

Biosynthesis and Transport of the Lantibiotic Mutacin 1140 Produced by Streptococcus mutans

et al. 2015

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Lantibiotics are ribosomally synthesized peptide antibiotics composed of an N-terminal leader peptide that is cleaved to yield the active antibacterial peptide. Significant advancements in molecular tools that promote the study of lantibiotic biosynthesis can be used in Streptococcus mutans. Herein, we further our understanding of leader peptide sequence and core peptide structural requirements for the biosynthesis and transport of the lantibiotic mutacin 1140. Our study on mutacin 1140 biosynthesis shows a dedicated secondary cleavage site within the leader peptide and the dependency of transport on core peptide posttranslational modifications (PTMs). The secondary cleavage site on the leader peptide is found at the ؊9 position, and secondary cleavage occurs before the core peptide is transported out of the cell. The coordinated cleavage at the ؊9 position was absent in a lanT deletion strain, suggesting that the core peptide interaction with the LanT transporter enables uniform cleavage at the ؊9 position. Following transport, the LanP protease was found to be tolerant to a wide variety of amino acid substitutions at the primary leader peptide cleavage site, with the exception of arginine at the ؊1 position. Several leader and core peptide mutations produced core peptide variants that had intermediate stages of PTM enzyme modifications, supporting the concept that PTM enzyme modifications, secondary cleavage, and transport are occurring in a highly coordinated fashion. IMPORTANCEMutacin 1140 belongs to the class I lantibiotic family of ribosomally synthesized and posttranslationally modified peptides (RiPPs). The biosynthesis of mutacin 1140 is a highly efficient process which does not lead to a discernible level of production of partially modified core peptide variants. The products isolated from an extensive mutagenesis study on the leader and core peptides of mutacin 1140 show that the posttranslational modifications (PTMs) on the core peptide occur under a highly coordinated dynamic process. PTMs are dictated by the distance of the core peptide modifiable residues from PTM enzyme active sites. The formation of lanthionine rings aids in the formation of successive PTMs, as was observed in a peptide variant lacking a Cterminal decarboxylation. Lantibiotics are a class of ribosomally synthesized peptide antibiotics produced by Gram-positive bacteria, such as Lactococcus lactis and Streptococcus mutans (1, 2). Lantibiotics are characterized by the presence of posttranslational modifications (PTMs), such as dehydrated residues and lanthionine rings. The modified residues 2,3-didehydroalanine (Dha) and 2,3-didehydrobutyrine (Dhb) are formed from dehydration of serines and threonines, respectively. The cyclization between a cysteine and either a Dha or a Dhb forms a lanthionine or a methyllanthionine ring, respectively. The biosynthetic gene cluster contains all the genes necessary to produce a lantibiotic. The lan operon for class I lantibiotics contains genes encoding the lantibiotic peptide (lanA); the...

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Gallidermin: a new lanthionine‐containing polypeptide antibiotic

Cited by 147 publications

References 18 publications

Analysis of membrane interactions of antibiotic peptides using ITC and biosensor measurements

Analysis of membrane interactions of antibiotic peptides using ITC and biosensor measurements

The Clostridium difficile cpr Locus Is Regulated by a Noncontiguous Two-Component System in Response to Type A and B Lantibiotics

Biosynthesis and Transport of the Lantibiotic Mutacin 1140 Produced by Streptococcus mutans

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