Morphogenetic Signaling Molecules of the Streptomycetes

Willey, Joanne M.; Gaskell, Alisa A.

doi:10.1021/cr1000404

Cited by 93 publications

(95 citation statements)

References 157 publications

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“…Conversely, many others may have other biological activities that remain to be revealed by future studies. Indeed, most of the class III lanthipeptides reported thus far from Actinobacteria have no or weak antimicrobial activities, and quite a few have anti-allodynic/antinociceptive activity (38,74) or morphogenetic activities (75). Since the venezuelins did not display antimicrobial activity in a previous study (16), class IV lanthipeptides may also have activities that would have eluded antimicrobial screens.…”

Section: Discussionmentioning

confidence: 96%

Expanded Natural Product Diversity Revealed by Analysis of Lanthipeptide-Like Gene Clusters in Actinobacteria

Zhang

Doroghazi

Zhao

et al. 2015

Appl Environ Microbiol

109

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Lanthionine-containing peptides (lanthipeptides) are a rapidly growing family of polycyclic peptide natural products belonging to the large class of ribosomally synthesized and posttranslationally modified peptides (RiPPs). Lanthipeptides are widely distributed in taxonomically distant species, and their currently known biosynthetic systems and biological activities are diverse. Building on the recent natural product gene cluster family (GCF) project, we report here large-scale analysis of lanthipeptidelike biosynthetic gene clusters from Actinobacteria. Our analysis suggests that lanthipeptide biosynthetic pathways, and by extrapolation the natural products themselves, are much more diverse than currently appreciated and contain many different posttranslational modifications. Furthermore, lanthionine synthetases are much more diverse in sequence and domain topology than currently characterized systems, and they are used by the biosynthetic machineries for natural products other than lanthipeptides. The gene cluster families described here significantly expand the chemical diversity and biosynthetic repertoire of lanthionine-related natural products. Biosynthesis of these novel natural products likely involves unusual and unprecedented biochemistries, as illustrated by several examples discussed in this study. In addition, class IV lanthipeptide gene clusters are shown not to be silent, setting the stage to investigate their biological activities. Lanthipeptides are a rapidly growing family of polycyclic peptides characterized by the presence of the thioether crosslinked amino acids lanthionine and methyllanthionine (1-5). These compounds are widely distributed in taxonomically distant species and display very diverse biological activities, ranging from antimicrobial to antiallodynic (5-7). Antibacterial lanthipeptides, such as the commercially used food preservative nisin, are termed lantibiotics (8). Lanthipeptides are generated from a ribosomally synthesized linear precursor peptide (generically termed LanA) and therefore belong to the large class of natural products that are ribosomally synthesized and posttranslationally modified peptides (RiPPs) (9). The precursor peptide LanA consists of a C-terminal core peptide where all posttranslational modifications take place and an N-terminal leader peptide that is important for posttranslational modifications and that is subsequently removed by proteolysis (10, 11). The installation of the (methyl)lanthionine thioether bridges is achieved by the initial dehydration of Ser and Thr residues in the precursor peptides, followed by stereoselective intramolecular Michael-type addition of Cys thiols to the newly formed dehydroamino acids (Fig. 1A).Four classes of biosynthetic enzymes are known to catalyze lanthionine formation (2, 12) (Fig. 1B). Class I lanthionine synthetases consist of a dehydratase and a cyclase that are generically termed LanB and LanC, respectively (8). Class II enzymes are generically named LanMs, which are single polypeptides containing an N-termi...

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Section: Discussionmentioning

confidence: 96%

Expanded Natural Product Diversity Revealed by Analysis of Lanthipeptide-Like Gene Clusters in Actinobacteria

Zhang

Doroghazi

Zhao

et al. 2015

Appl Environ Microbiol

109

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“…The genes for glucose kinase and for the glycolytic enzymes were not changed significantly. Besides the primary metabolic genes discussed above, another class of genes that was deregulated in the rok7B7 null mutant was that of the chpABCDEFGH, rdlAB, and ramS genes, which encode the surfactant proteins chaplins, rodlins, and the spore-associated protein SapB, respectively (55,56). All of these genes showed the same trend, but transcription of chpDEH and rdlAB was most strongly downregulated, namely, over 2-fold at 42 h compared to the parental strain M145 (see Table S4).…”

Section: Figmentioning

confidence: 99%

The ROK Family Regulator Rok7B7 Pleiotropically Affects Xylose Utilization, Carbon Catabolite Repression, and Antibiotic Production in Streptomyces coelicolor

Świątek

Gubbens

Bucca

et al. 2013

Journal of Bacteriology

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cMembers of the ROK family of proteins are mostly transcriptional regulators and kinases that generally relate to the control of primary metabolism, whereby its member glucose kinase acts as the central control protein in carbon control in Streptomyces. Here, we show that deletion of SCO6008 (rok7B7) strongly affects carbon catabolite repression (CCR), growth, and antibiotic production in Streptomyces coelicolor. Deletion of SCO7543 also affected antibiotic production, while no major changes were observed after deletion of the rok family genes SCO0794, SCO1060, SCO2846, SCO6566, or SCO6600. Global expression profiling of the rok7B7 mutant by proteomics and microarray analysis revealed strong upregulation of the xylose transporter operon xylFGH, which lies immediately downstream of rok7B7, consistent with the improved growth and delayed development of the mutant on xylose. The enhanced CCR, which was especially obvious on rich or xylose-containing media, correlated with elevated expression of glucose kinase and of the glucose transporter GlcP. In liquid-grown cultures, expression of the biosynthetic enzymes for production of prodigionines, siderophores, and calcium-dependent antibiotic (CDA) was enhanced in the mutant, and overproduction of prodigionines was corroborated by matrixassisted laser desorption ionization-time-of-flight analysis. These data present Rok7B7 as a pleiotropic regulator of growth, CCR, and antibiotic production in Streptomyces.

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“…For instance, quorum-sensing compounds such as acyl-homoserine lactones allow microbes to modulate their gene expression in response to cellular density and are frequently involved in regulating biofilm formation (1,2). Another example is the developmental signaling cue goadsporin, which controls cellular development in Streptomyces species (3,4). Compounds secreted by microbes can also act as interspecific signaling cues, altering microbial development in other bacterial species (5)(6)(7)(8).…”

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confidence: 99%

Inhibition of Cell Differentiation in Bacillus subtilis by Pseudomonas protegens

Powers¹,

Sanabria-Valentín²,

Bowers³

et al. 2015

J. Bacteriol.

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Interspecies interactions have been described for numerous bacterial systems, leading to the identification of chemical compounds that impact bacterial physiology and differentiation for processes such as biofilm formation. Here, we identified soil microbes that inhibit biofilm formation and sporulation in the common soil bacterium Bacillus subtilis. We did so by creating a reporter strain that fluoresces when the transcription of a biofilm-specific gene is repressed. Using this reporter in a coculture screen, we identified Pseudomonas putida and Pseudomonas protegens as bacteria that secrete compounds that inhibit biofilm gene expression in B. subtilis. The active compound produced by P. protegens was identified as the antibiotic and antifungal molecule 2,4-diacetylphloroglucinol (DAPG). Colonies of B. subtilis grown adjacent to a DAPG-producing P. protegens strain had altered colony morphologies relative to B. subtilis colonies grown next to a DAPG-null P. protegens strain (phlD strain). Using a subinhibitory concentration of purified DAPG in a pellicle assay, we saw that biofilm-specific gene transcription was delayed relative to transcription in untreated samples. These transcriptional changes also corresponded to phenotypic alterations: both biofilm biomass and spore formation were reduced in B. subtilis liquid cultures treated with subinhibitory concentrations of DAPG. Our results add DAPG to the growing list of antibiotics that impact bacterial development and physiology at subinhibitory concentrations. These findings also demonstrate the utility of using coculture as a means to uncover chemically mediated interspecies interactions between bacteria. IMPORTANCEBiofilms are communities of bacteria adhered to surfaces by an extracellular matrix; such biofilms can have important effects in both clinical and agricultural settings. To identify chemical compounds that inhibited biofilm formation, we used a fluorescent reporter to screen for bacteria that inhibited biofilm gene expression in Bacillus subtilis. We identified Pseudomonas protegens as one such bacterium and found that the biofilm-inhibiting compound it produces was the antibiotic 2,4-diacetylphloroglucinol (DAPG). We showed that even at subinhibitory concentrations, DAPG inhibits biofilm formation and sporulation in B. subtilis. These findings have potential implications for understanding the interactions between these two microbes in the natural world and support the idea that many compounds considered antibiotics can impact bacterial development at subinhibitory concentrations.

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Morphogenetic Signaling Molecules of the Streptomycetes

Cited by 93 publications

References 157 publications

Expanded Natural Product Diversity Revealed by Analysis of Lanthipeptide-Like Gene Clusters in Actinobacteria

Expanded Natural Product Diversity Revealed by Analysis of Lanthipeptide-Like Gene Clusters in Actinobacteria

The ROK Family Regulator Rok7B7 Pleiotropically Affects Xylose Utilization, Carbon Catabolite Repression, and Antibiotic Production in Streptomyces coelicolor

Inhibition of Cell Differentiation in Bacillus subtilis by Pseudomonas protegens

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