Screening genomes of Gram-positive bacteria for double-glycine-motif-containing peptides

Dirix, Gunter; Monsieurs, Pieter; Marchal, Kathleen; Vanderleyden, Jozef; Michiels, Jan

doi:10.1099/mic.0.27040-0

Cited by 34 publications

(28 citation statements)

References 23 publications

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“…There could be even more, as pointed out by a recent survey (7). The finding of so many type II bacteriocins raises several questions: (i) towards which species are these bacteriocins active, (ii) under what conditions are they expressed, and (iii) is the production of bacteriocins relevant for colonization or survival of S. mutans in dental plaque?…”

Section: Discussionmentioning

confidence: 98%

Regulation of Bacteriocin Production in Streptococcus mutans by the Quorum-Sensing System Required for Development of Genetic Competence

2005

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In Streptococcus mutans, competence for genetic transformation and biofilm formation are dependent on the two-component signal transduction system ComDE together with the inducer peptide pheromone competencestimulating peptide (CSP) (encoded by comC). Here, it is shown that the same system is also required for expression of the nlmAB genes, which encode a two-peptide nonlantibiotic bacteriocin. Expression from a transcriptional nlmAB-lacZ fusion was highest at high cell density and was increased up to 60-fold following addition of CSP, but it was abolished when the comDE genes were interrupted. Two more genes, encoding another putative bacteriocin and a putative bacteriocin immunity protein, were also regulated by this system. The regions upstream of these genes and of two further putative bacteriocin-encoding genes and a gene encoding a putative bacteriocin immunity protein contained a conserved 9-bp repeat element just upstream of the transcription start, which suggests that expression of these genes is also dependent on the ComCDE regulatory system. Mutations in the repeat element of the nlmAB promoter region led to a decrease in CSP-dependent expression of nlmAB-lacZ. In agreement with these results, a comDE mutant and mutants unable to synthesize or export CSP did not produce bacteriocins. It is speculated that, at high cell density, bacteriocin production is induced to liberate DNA from competing streptococci.

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Section: Discussionmentioning

confidence: 98%

Regulation of Bacteriocin Production in Streptococcus mutans by the Quorum-Sensing System Required for Development of Genetic Competence

2005

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“…5A). Two arguments supporting this site as the putative leader peptide processing site are that (i) cleavage between or before the Ala residues is unlikely, given the molecular mass of the resultant peptide and the number of modifiable residues, and (ii) bacteriocin leader peptides are most often processed after a Gly-Gly sequence, but other small residues, such as Ser and Ala, can be found directly N terminal to the scissile bond (13,28,35).…”

Section: Vol 193 2011 Novel Microcin From B Amyloliquefaciens Fzb4mentioning

confidence: 99%

Plantazolicin, a Novel Microcin B17/Streptolysin S-Like Natural Product from Bacillus amyloliquefaciens FZB42

et al. 2011

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Here we report on a novel thiazole/oxazole-modified microcin (TOMM) from Bacillus amyloliquefaciens FZB42, a Gram-positive soil bacterium. This organism is well known for stimulating plant growth and biosynthesizing complex small molecules that suppress the growth of bacterial and fungal plant pathogens. Like microcin B17 and streptolysin S, the TOMM from B. amyloliquefaciens FZB42 undergoes extensive posttranslational modification to become a bioactive natural product. Our data show that the modified peptide bears a molecular mass of 1,335 Da and displays antibacterial activity toward closely related Gram-positive bacteria. A cluster of 12 genes that covers ϳ10 kb is essential for the production, modification, export, and self-immunity of this natural product. We have named this compound plantazolicin (PZN), based on the association of several producing organisms with plants and the incorporation of azole heterocycles, which derive from Cys, Ser, and Thr residues of the precursor peptide.Bacillus amyloliquefaciens FZB42 is a Gram-positive, plant growth-promoting bacterium with an impressive capacity to produce secondary metabolites with antimicrobial activity (7). The nonribosomal syntheses of polyketides (bacillaene, difficidin, and macrolactin), lipopeptides (surfactin, fengycin, and bacillomycin D), and siderophores (bacillibactin and the product of the nrs cluster) are carried out by large gene clusters distributed over the entire genome of B. amyloliquefaciens FZB42. While these compounds are biosynthesized in a 4Ј-phosphopantetheine transferase (Sfp)-dependent fashion, the production of the antibacterial dipeptide bacilysin is independent of Sfp (8,9). In total, 8.5% of the entire genomic capacity of B. amyloliquefaciens FZB42 is devoted to the nonribosomal synthesis of secondary metabolites, exceeding that of the model Gram-positive bacterium Bacillus subtilis 168 by more than 2-fold (6). Prophage sequences that often harbor biosynthetic gene clusters of ribosomally synthesized peptides (microcins, lantibiotics/lantipeptides), which are common in B. subtilis strains, were not previously detected within the FZB42 genome. However, the presence of an antimicrobial compound(s) active against sigW mutant strain HB0042 of B. subtilis has been reported. SigW is an extracytoplasmic sigma factor that provides intrinsic resistance to antimicrobial compounds produced by other Bacilli (4).The driving force for the current report was the finding that FZB42 mutant RS6, which is deficient in the Sfp-dependent synthesis of lipopeptides and polyketides and in Sfp-independent bacilysin production (9), still produced an antibacterial substance active against Bacillus subtilis HB0042. This finding underscores the diversity of biosynthetic strategies employed by FZB42 and offers new possibilities for discovering novel natural products with biomedically relevant activities. Recent genomic analysis of FZB42 revealed a ribosomally encoded biosynthetic gene cluster that is conserved among many species across two domains of life ...

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“…1B), which some studies show is important for the maturation of the core peptide antibiotic (19,20,23). Class II lantibiotics contain a GG or GA which is used as a cleavage site for the removal of the leader peptide from the core peptide and contain an upstream EV and/or EL conserved sequence motif (24,25). Amino acid substitutions in the conserved regions within the leader peptide have shown that the composition of these common motifs is important for the maturation of the core peptide, while a vast majority of the leader peptide does not have any amino acid sequence specificity (19,20,26,27).…”

mentioning

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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Screening genomes of Gram-positive bacteria for double-glycine-motif-containing peptides

Cited by 34 publications

References 23 publications

Regulation of Bacteriocin Production in Streptococcus mutans by the Quorum-Sensing System Required for Development of Genetic Competence

Regulation of Bacteriocin Production in Streptococcus mutans by the Quorum-Sensing System Required for Development of Genetic Competence

Plantazolicin, a Novel Microcin B17/Streptolysin S-Like Natural Product from Bacillus amyloliquefaciens FZB42

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

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