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Organic Letters Feb 2014A synthesis of carolacton, a myxobacterial natural product that has profound effects on Streptococcus mutans biofilms, is reported. The synthesis proceeds via a longest...
A synthesis of carolacton, a myxobacterial natural product that has profound effects on Streptococcus mutans biofilms, is reported. The synthesis proceeds via a longest linear sequence of 14 steps from an Evans β-ketoimide and enabled preliminary evaluations of the effects of late-stage intermediates on S. mutans biofilms. These studies suggest that further investigations into carolacton's structure-function relationships are warranted.
Topics: Biofilms; Macrolides; Molecular Structure; Myxococcales; Streptococcus mutans
PubMed: 24483250
DOI: 10.1021/ol500004k -
Current Microbiology Dec 2022Mangroves are unique intertidal ecosystems that provide ecological niches to different microbes, which play various roles in nutrient recycling and diverse environmental...
Mangroves are unique intertidal ecosystems that provide ecological niches to different microbes, which play various roles in nutrient recycling and diverse environmental activities. The association between myxobacteria and mangroves are hitherto poorly understood. The aim of our study was to evaluate the myxobacterial community composition as well as isolate myxobacteria and to characterize the antimicrobial activity of myxobacteria isolates from Indonesian mangroves. Twenty-five cultivable myxobacteria were affiliated in six genera: Myxococcus, Corallococcus, Archangium, Chondromyces, Racemicystis and Nannocystis of the order Myxococcales based on partial 16S rRNA gene sequences. Thirteen crude extracts showed moderate activities against at least one of human pathogenic microorganisms. The crude extract of Racemicystis sp. strain 503MSO indicated a novel compound, which has not been reported in the database yet and the identification of this compound needs further study. The myxobacterial communities of three different sampling sites were analyzed using primers adapted for the myxobacteria group identification. The results showed that myxobacterial communities are more diverse than assumed. Therefore, our study has highlighted the importance of the mangrove habitat as promising harbor of myxobacteria as well as novel antimicrobial compounds with activity against pathogenic microorganisms.
Topics: Humans; Myxococcales; Ecosystem; Soil Microbiology; Indonesia; RNA, Ribosomal, 16S; Phylogeny; Anti-Infective Agents
PubMed: 36538090
DOI: 10.1007/s00284-022-03066-2 -
PloS One 2016Myxobacteria, a group of Gram-negative aerobes, belong to the class δ-proteobacteria and order Myxococcales. Unlike anaerobic δ-proteobacteria, they exhibit several...
Myxobacteria, a group of Gram-negative aerobes, belong to the class δ-proteobacteria and order Myxococcales. Unlike anaerobic δ-proteobacteria, they exhibit several unusual physiogenomic properties like gliding motility, desiccation-resistant myxospores and large genomes with high coding density. Here we report a 9.5 Mbp complete genome of Myxococcus hansupus that encodes 7,753 proteins. Phylogenomic and genome-genome distance based analysis suggest that Myxococcus hansupus is a novel member of the genus Myxococcus. Comparative genome analysis with other members of the genus Myxococcus was performed to explore their genome diversity. The variation in number of unique proteins observed across different species is suggestive of diversity at the genus level while the overrepresentation of several Pfam families indicates the extent and mode of genome expansion as compared to non-Myxococcales δ-proteobacteria.
Topics: Genome, Bacterial; Myxococcus; Phylogeny; Sequence Analysis, DNA
PubMed: 26900859
DOI: 10.1371/journal.pone.0148593 -
Chemistry (Weinheim An Der Bergstrasse,... Dec 2021A metabolome-guided screening approach in the novel myxobacterium Corallococcus sp. MCy9072 resulted in the isolation of the unprecedented natural product myxofacycline...
A metabolome-guided screening approach in the novel myxobacterium Corallococcus sp. MCy9072 resulted in the isolation of the unprecedented natural product myxofacycline A, which features a rare isoxazole substructure. Identification and genomic investigation of additional producers alongside targeted gene inactivation experiments and heterologous expression of the corresponding biosynthetic gene cluster in the host Myxococcus xanthus DK1622 confirmed a noncanonical megaenzyme complex as the biosynthetic origin of myxofacycline A. Induced expression of the respective genes led to significantly increased production titers enabling the identification of six further members of the myxofacycline natural product family. Whereas myxofacyclines A-D display an isoxazole substructure, intriguingly myxofacyclines E and F were found to contain 4-pyrimidinole, a heterocycle unprecedented in natural products. Lastly, myxofacycline G features another rare 1,2-dihydropyrol-3-one moiety. In addition to a full structure elucidation, we report the underlying biosynthetic machinery and present a rationale for the formation of all myxofacyclines. Unexpectedly, an extraordinary polyketide synthase-nonribosomal peptide synthetase hybrid was found to produce all three types of heterocycle in these natural products.
Topics: Multigene Family; Myxococcales; Myxococcus xanthus; Polyketide Synthases; Polyketides
PubMed: 34617331
DOI: 10.1002/chem.202103095 -
Scientific Reports Feb 2021Considered a key taxon in soil and marine microbial communities, myxobacteria exist as coordinated swarms that utilize a combination of lytic enzymes and specialized...
Considered a key taxon in soil and marine microbial communities, myxobacteria exist as coordinated swarms that utilize a combination of lytic enzymes and specialized metabolites to facilitate predation of microbes. This capacity to produce specialized metabolites and the associated abundance of biosynthetic pathways contained within their genomes have motivated continued drug discovery efforts from myxobacteria. Of all myxobacterial biosynthetic gene clusters deposited in the antiSMASH database, only one putative acylhomoserine lactone (AHL) synthase, agpI, was observed, in genome data from Archangium gephyra. Without an AHL receptor also apparent in the genome of A. gephyra, we sought to determine if AgpI was an uncommon example of an orphaned AHL synthase. Herein we report the bioinformatic assessment of AgpI and discovery of a second AHL synthase from Vitiosangium sp. During axenic cultivation conditions, no detectible AHL metabolites were observed in A. gephyra extracts. However, heterologous expression of each synthase in Escherichia coli provided detectible quantities of 3 AHL signals including 2 known AHLs, C8-AHL and C9-AHL. These results suggest that A. gephyra AHL production is dormant during axenic cultivation. The functional, orphaned AHL synthase, AgpI, is unique to A. gephyra, and its utility to the predatory myxobacterium remains unknown.
Topics: Acyl-Butyrolactones; Escherichia coli; Ligases; Myxococcales; Phylogeny; Quorum Sensing; Sequence Analysis, DNA
PubMed: 33542315
DOI: 10.1038/s41598-021-82480-1 -
Scientific Reports Aug 2021Predation contributes to the structure and diversity of microbial communities. Predatory myxobacteria are ubiquitous to a variety of microbial habitats and capably...
Predation contributes to the structure and diversity of microbial communities. Predatory myxobacteria are ubiquitous to a variety of microbial habitats and capably consume a broad diversity of microbial prey. Predator-prey experiments utilizing myxobacteria have provided details into predatory mechanisms and features that facilitate consumption of prey. However, prey resistance to myxobacterial predation remains underexplored, and prey resistances have been observed exclusively from predator-prey experiments that included the model myxobacterium Myxococcus xanthus. Utilizing a predator-prey pairing that instead included the myxobacterium, Cystobacter ferrugineus, with Pseudomonas putida as prey, we observed surviving phenotypes capable of eluding predation. Comparative transcriptomics between P. putida unexposed to C. ferrugineus and the survivor phenotype suggested that increased expression of efflux pumps, genes associated with mucoid conversion, and various membrane features contribute to predator avoidance. Unique features observed from the survivor phenotype when compared to the parent P. putida include small colony variation, efflux-mediated antibiotic resistance, phenazine-1-carboxylic acid production, and increased mucoid conversion. These results demonstrate the utility of myxobacterial predator-prey models and provide insight into prey resistances in response to predatory stress that might contribute to the phenotypic diversity and structure of bacterial communities.
Topics: Animals; Culture Media; Drug Resistance, Bacterial; Genes, Bacterial; Genomics; Myxococcales; Oligopeptides; Predatory Behavior; Pseudomonas putida
PubMed: 34385565
DOI: 10.1038/s41598-021-96046-8 -
Visualization of Bacterial Microcompartment Facet Assembly Using High-Speed Atomic Force Microscopy.Nano Letters Mar 2016Bacterial microcompartments (BMCs) are proteinaceous organelles widespread among bacterial phyla. They compartmentalize enzymes within a selectively permeable shell and...
Bacterial microcompartments (BMCs) are proteinaceous organelles widespread among bacterial phyla. They compartmentalize enzymes within a selectively permeable shell and play important roles in CO2 fixation, pathogenesis, and microbial ecology. Here, we combine X-ray crystallography and high-speed atomic force microscopy to characterize, at molecular resolution, the structure and dynamics of BMC shell facet assembly. Our results show that preformed hexamers assemble into uniformly oriented shell layers, a single hexamer thick. We also observe the dynamic process of shell facet assembly. Shell hexamers can dissociate from and incorporate into assembled sheets, indicating a flexible intermolecular interaction. Furthermore, we demonstrate that the self-assembly and dynamics of shell proteins are governed by specific contacts at the interfaces of shell proteins. Our study provides novel insights into the formation, interactions, and dynamics of BMC shell facets, which are essential for the design and engineering of self-assembled biological nanoreactors and scaffolds based on BMC architectures.
Topics: Bacterial Proteins; Crystallography, X-Ray; Microscopy, Atomic Force; Myxococcales; Point Mutation; Protein Conformation
PubMed: 26617073
DOI: 10.1021/acs.nanolett.5b04259 -
Structure (London, England : 1993) May 2019Bacterial microcompartments (BMCs) are composed of an enzymatic core encapsulated by a selectively permeable protein shell that enhances catalytic efficiency. Many...
Bacterial microcompartments (BMCs) are composed of an enzymatic core encapsulated by a selectively permeable protein shell that enhances catalytic efficiency. Many pathogenic bacteria derive competitive advantages from their BMC-based catabolism, implicating BMCs as drug targets. BMC shells are of interest for bioengineering due to their diverse and selective permeability properties and because they self-assemble. A complete understanding of shell composition and organization is a prerequisite for biotechnological applications. Here, we report the cryoelectron microscopy structure of a BMC shell at 3.0-Å resolution, using an image-processing strategy that allowed us to determine the previously uncharacterized structural details of the interactions formed by the BMC-T and BMC-T shell subunits in the context of the assembled shell. We found unexpected structural plasticity among these interactions, resulting in distinct shell populations assembled from varying numbers of the BMC-T and BMC-T subunits. We discuss the implications of these findings on shell assembly and function.
Topics: Algorithms; Bacterial Proteins; Cryoelectron Microscopy; Ligands; Metabolome; Myxococcales; Organelles; Permeability; Protein Multimerization; Protein Structure, Secondary; Software
PubMed: 30833088
DOI: 10.1016/j.str.2019.01.017 -
Proceedings of the National Academy of... Oct 2008Ser/Thr/Tyr kinases, which together comprise a major class of regulatory proteins in eukaryotes, were not believed to play an important role in prokaryotes until...
Ser/Thr/Tyr kinases, which together comprise a major class of regulatory proteins in eukaryotes, were not believed to play an important role in prokaryotes until recently. However, our analysis of 626 prokaryotic genomes reveals that eukaryotic-like protein kinases (ELKs) are found in nearly two-thirds of the sequenced strains. We have identified 2697 ELKs, most of which are encoded by multicellular strains of the phyla Proteobacteria (Myxococcales), Actinobacteria, Cyanobacteria, and Chloroflexi, and 2 Acidobacteria and 1 Planctomycetes. Astonishingly, 7 myxobacterial strains together encode 892 ELKs, with 4 of the strains exhibiting a genomic ELK density similar to that observed in eukaryotes. Most myxobacterial ELKs show a modular organization in which the kinase domain is located at the N terminus. The C-terminal portion of the ELKs is highly diverse and often contains sequences with similarity to characterized domains, most of them involved in signaling mechanisms or in protein-protein interactions. However, many of these architectures are unique to the myxobacteria, an observation that suggests that this group exploits sophisticated and novel signal transduction systems. Phylogenetic reconstruction using the kinase domains revealed many orthologous sequence pairs and a huge number of gene duplications that probably occurred after speciation. Furthermore, studies of the microsynteny in the ELK-encoding regions reveal only low levels of synteny among Myxococcus xanthus, Plesiocystis pacifica, and Sorangium cellulosum. However, extensive similarities between M. xanthus, Stigmatella aurantiaca, and 3 Anaeromyxobacter strains were observed, indicating that they share regulatory pathways involving various ELKs.
Topics: Bacterial Proteins; Gene Duplication; Myxococcales; Phylogeny; Prokaryotic Cells; Protein Kinases; Signal Transduction; Synteny
PubMed: 18836084
DOI: 10.1073/pnas.0806851105 -
Chemical Communications (Cambridge,... Jul 2016C-methyltransferases (MTs) from modular polyketide synthase assembly lines are relatively rare and unexplored domains that are responsible for installing α-methyl...
C-methyltransferases (MTs) from modular polyketide synthase assembly lines are relatively rare and unexplored domains that are responsible for installing α-methyl groups into nascent polyketide backbones. The stage at which these synthase-embedded enzymes operate during polyketide biosynthesis has yet to be conclusively demonstrated. In this work we establish the activity and substrate preference for six MTs from the gephyronic acid polyketide synthase and demonstrate their ability to methylate both N-acetylcysteamine- and acyl carrier protein-linked β-ketoacylthioester substrates but not malonyl thioester equivalents. These data strongly indicate that MT-catalyzed methylation occurs immediately downstream of ketosynthase-mediated condensation during polyketide assembly. This work represents the first successful report of MT-catalyzed mono- and dimethylation of simple thioester substrates and provides the groundwork for future mechanistic and engineering studies on this important but poorly understood enzymatic domain.
Topics: Biocatalysis; Fatty Acids, Monounsaturated; Methylation; Molecular Conformation; Myxococcales; Polyketide Synthases
PubMed: 27346052
DOI: 10.1039/c6cc04418b