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1.
Database (Oxford) ; 20242024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38958433

RESUMEN

Myxobacteria are predatory bacteria with antimicrobial activity, utilizing complex mechanisms to kill their prey and assimilate their macromolecules. Having large genomes encoding hundreds of secondary metabolites, hydrolytic enzymes and antimicrobial peptides, these organisms are widely studied for their antibiotic potential. MyxoPortal is a comprehensive genomic database hosting 262 genomes of myxobacterial strains. Datasets included provide genome annotations with gene locations, functions, amino acids and nucleotide sequences, allowing analysis of evolutionary and taxonomical relationships between strains and genes. Biosynthetic gene clusters are identified by AntiSMASH, and dbAMP-generated antimicrobial peptide sequences are included as a resource for novel antimicrobial discoveries, while curated datasets of CRISPR/Cas genes, regulatory protein sequences, and phage associated genes give useful insights into each strain's biological properties. MyxoPortal is an intuitive open-source database that brings together application-oriented genomic features that can be used in taxonomy, evolution, predation and antimicrobial research. MyxoPortal can be accessed at http://dicsoft1.physics.iisc.ac.in/MyxoPortal/. Database URL:  http://dicsoft1.physics.iisc.ac.in/MyxoPortal/. Graphical Abstract.


Asunto(s)
Bases de Datos Genéticas , Genoma Bacteriano , Myxococcales , Myxococcales/genética , Genómica/métodos
2.
Adv Microb Physiol ; 85: 1-55, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39059819

RESUMEN

Myxobacteria (phylum Myxococcota) are abundant and virtually ubiquitous microbial predators. Facultatively multicellular organisms, they are able to form multicellular fruiting bodies and swarm across surfaces, cooperatively hunting for prey. Myxobacterial communities are able to kill a wide range of prey microbes, assimilating their biomass to fuel population growth. Their mechanism of predation is exobiotic - hydrolytic enzymes and toxic metabolites are secreted into the extracellular environment, killing and digesting prey cells from without. However, recent observations of single-cell predation and contact-dependent prey killing challenge the dogma of myxobacterial predation being obligately cooperative. Regardless of their predatory mechanisms, myxobacteria have a broad prey range, which includes Gram-negative bacteria, Gram-positive bacteria and fungi. Pangenome analyses have shown that their extremely large genomes are mainly composed of accessory genes, which are not shared by all members of their species. It seems that the diversity of accessory genes in different strains provides the breadth of activity required to prey upon such a smorgasbord of microbes, and also explains the considerable strain-to-strain variation in predatory efficiency against specific prey. After providing a short introduction to general features of myxobacterial biology which are relevant to predation, this review brings together a rapidly growing body of work into the molecular mechanisms and genetic basis of predation, presenting a summary of current knowledge, highlighting trends in research and suggesting strategies by which we can potentially exploit myxobacterial predation in the future.


Asunto(s)
Myxococcales , Myxococcales/genética , Myxococcales/metabolismo , Genoma Bacteriano
3.
Org Lett ; 26(30): 6359-6363, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39037587

RESUMEN

Innovative discovery approaches such as genome-mining and metabolomics-inspired methods have reshaped the natural product research field, complementing traditional bioactivity-based screens and allowing hitherto unseen compounds to be uncovered from previously investigated producers. In line with these trends, we report here imidacins, a novel class of secondary metabolites specific to the myxobacterial genus Stigmatella. A combination of secondary metabolome analysis, genome-mining techniques, spectroscopic analysis, and finally total synthesis was used to allow structure elucidation. Imidacins are urocanate-derived aliphatic acids with an adjacent cyclopropane moiety, structural features unprecedented in natural products to date.


Asunto(s)
Stigmatella aurantiaca , Estructura Molecular , Stigmatella aurantiaca/química , Alcaloides/química , Alcaloides/síntesis química , Productos Biológicos/química , Productos Biológicos/farmacología , Productos Biológicos/síntesis química , Myxococcales/química , Ciclopropanos/química , Ciclopropanos/farmacología , Ciclopropanos/síntesis química
4.
Biomolecules ; 14(6)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38927063

RESUMEN

The Ebola virus (EBOV) is a lethal pathogen causing hemorrhagic fever syndrome which remains a global health challenge. In the EBOV, two multifunctional proteins, VP35 and VP40, have significant roles in replication, virion assembly, and budding from the cell and have been identified as druggable targets. In this study, we employed in silico methods comprising molecular docking, molecular dynamic simulations, and pharmacological properties to identify prospective drugs for inhibiting VP35 and VP40 proteins from the myxobacterial bioactive natural product repertoire. Cystobactamid 934-2, Cystobactamid 919-1, and Cittilin A bound firmly to VP35. Meanwhile, 2-Hydroxysorangiadenosine, Enhypyrazinone B, and Sorangiadenosine showed strong binding to the matrix protein VP40. Molecular dynamic simulations revealed that, among these compounds, Cystobactamid 919-1 and 2-Hydroxysorangiadenosine had stable interactions with their respective targets. Similarly, molecular mechanics Poisson-Boltzmann surface area (MMPBSA) calculations indicated close-fitting receptor binding with VP35 or VP40. These two compounds also exhibited good pharmacological properties. In conclusion, we identified Cystobactamid 919-1 and 2-Hydroxysorangiadenosine as potential ligands for EBOV that target VP35 and VP40 proteins. These findings signify an essential step in vitro and in vivo to validate their potential for EBOV inhibition.


Asunto(s)
Antivirales , Productos Biológicos , Ebolavirus , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Ebolavirus/efectos de los fármacos , Productos Biológicos/farmacología , Productos Biológicos/química , Antivirales/farmacología , Antivirales/química , Myxococcales/química , Humanos , Proteínas Reguladoras y Accesorias Virales/antagonistas & inhibidores , Proteínas Reguladoras y Accesorias Virales/metabolismo , Proteínas Reguladoras y Accesorias Virales/química , Proteínas de la Matriz Viral/antagonistas & inhibidores , Proteínas de la Matriz Viral/metabolismo , Proteínas de la Matriz Viral/química , Proteínas de la Nucleocápside
5.
J Microbiol ; 62(6): 463-471, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38872008

RESUMEN

Archangium gephyra KYC5002 produces tubulysins during the death phase. In this study, we aimed to determine whether dead cells produce tubulysins. Cells were cultured for three days until the verge of the death phase, disrupted via ultrasonication, incubated for 2 h, and examined for tubulysin production. Non-disrupted cells produced 0.14 mg/L of tubulysin A and 0.11 mg/L of tubulysin B. Notably, tubulysin A production was increased by 4.4-fold to 0.62 mg/L and that of tubulysin B was increased by 6.7-fold to 0.74 mg/L in the disrupted cells. The same increase in tubulysin production was observed when the cells were killed by adding hydrogen peroxide. However, when the enzymes were inactivated via heat treatment of the cultures at 65 °C for 30 min, no significant increase in tubulysin production due to cell death was observed. Reverse transcription-quantitative polymerase chain reaction analysis of tubB mRNA revealed that the expression levels of tubulysin biosynthetic enzyme genes increased during the death phase compared to those during the vegetative growth phase. Our findings suggest that A. gephyra produces biosynthetic enzymes and subsequently uses them for tubulysin production in the cell death phase or during cell lysis by predators.


Asunto(s)
Myxococcales , Myxococcales/metabolismo , Myxococcales/genética , Peróxido de Hidrógeno/metabolismo , Muerte Celular
6.
Arch Microbiol ; 206(7): 317, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904779

RESUMEN

Two myxobacterial strains (KH5-1T and NO1) were isolated from the activated sludge tanks treating municipal sewage wastewater in Japan. These strains were recognised as myxobacteria based on their phenotypic characteristics of swarming colonies and fruiting bodies. Phylogenetic analyses using the 16S rRNA gene revealed that strains KH5-1T and NO1 were affiliated with the genus Corallococcus, with the closest neighbours being Corallococcus exercitus AB043AT (99.77% and 99.84%, respectively). Genome comparisons using orthologous average nucleotide identity (orthoANI) and digital DNA-DNA hybridisation similarity (dDDH) with strains KH5-1T and NO1 and their phylogenetically close relatives in Corallococcus spp. were below the thresholds. The major cellular fatty acids of strains KH5-1T and NO1 were iso-C15:0 (31.9%, 30.0%), summed feature 3 (comprising C16:1ω7c and/or C16:1ω6c) (20.2%, 17.7%), and iso-C17:0 (12.1%, 14.8%), and the major respiratory quinone was found to be menaquinone (MK)-8. Based on the phenotypic, chemotaxonomic, and phylogenetic evidence, strains KH5-1T and NO1 represent a new species in the genus Corallococcus, for which the proposed name is Corallococcus caeni sp. nov. The type strain is KH5-1T (= NCIMB 15510T = JCM 36609T).


Asunto(s)
Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Myxococcales , Filogenia , ARN Ribosómico 16S , Aguas del Alcantarillado , Aguas del Alcantarillado/microbiología , ARN Ribosómico 16S/genética , Ácidos Grasos/análisis , ADN Bacteriano/genética , Myxococcales/genética , Myxococcales/clasificación , Myxococcales/aislamiento & purificación , Japón , Hibridación de Ácido Nucleico , Análisis de Secuencia de ADN , Vitamina K 2/análisis , Genoma Bacteriano , Aguas Residuales/microbiología
7.
mSystems ; 9(6): e0121023, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38747603

RESUMEN

The clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) system widely occurs in prokaryotic organisms to recognize and destruct genetic invaders. Systematic collation and characterization of endogenous CRISPR-Cas systems are conducive to our understanding and potential utilization of this natural genetic machinery. In this study, we screened 39 complete and 692 incomplete genomes of myxobacteria using a combined strategy to dispose of the abridged genome information and revealed at least 19 CRISPR-Cas subtypes, which were distributed with a taxonomic difference and often lost stochastically in intraspecies strains. The cas genes in each subtype were evolutionarily clustered but deeply separated, while most of the CRISPRs were divided into four types based on the motif characteristics of repeat sequences. The spacers recorded in myxobacterial CRISPRs were in high G+C content, matching lots of phages, tiny amounts of plasmids, and, surprisingly, massive organismic genomes. We experimentally demonstrated the immune and self-target immune activities of three endogenous systems in Myxococcus xanthus DK1622 against artificial genetic invaders and revealed the microhomology-mediated end-joining mechanism for the immunity-induced DNA repair but not homology-directed repair. The panoramic view and immune activities imply potential omnipotent immune functions and applications of the endogenous CRISPR-Cas machinery. IMPORTANCE: Serving as an adaptive immune system, clustered regularly interspaced short palindromic repeats and their associated proteins (CRISPR-Cas) empower prokaryotes to fend off the intrusion of external genetic materials. Myxobacteria are a collective of swarming Gram-stain-negative predatory bacteria distinguished by intricate multicellular social behavior. An in-depth analysis of their intrinsic CRISPR-Cas systems is beneficial for our understanding of the survival strategies employed by host cells within their environmental niches. Moreover, the experimental findings presented in this study not only suggest the robust immune functions of CRISPR-Cas in myxobacteria but also their potential applications.


Asunto(s)
Sistemas CRISPR-Cas , Genoma Bacteriano , Myxococcales , Sistemas CRISPR-Cas/genética , Genoma Bacteriano/genética , Myxococcales/genética , Filogenia , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética
8.
Mol Biol Evol ; 41(5)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38717941

RESUMEN

Prokaryotes dominate the Tree of Life, but our understanding of the macroevolutionary processes generating this diversity is still limited. Habitat transitions are thought to be a key driver of prokaryote diversity. However, relatively little is known about how prokaryotes successfully transition and persist across environments, and how these processes might vary between biomes and lineages. Here, we investigate biome transitions and specialization in natural populations of a focal bacterial phylum, the Myxococcota, sampled across a range of replicated soils and freshwater and marine sediments in Cornwall (UK). By targeted deep sequencing of the protein-coding gene rpoB, we found >2,000 unique Myxococcota lineages, with the majority (77%) classified as biome specialists and with only <5% of lineages distributed across the salt barrier. Discrete character evolution models revealed that specialists in one biome rarely transitioned into specialists in another biome. Instead, evolved generalism mediated transitions between biome specialists. State-dependent diversification models found variation in speciation rates across the tree, but this variation was independent of biome association or specialization. Our findings were robust to phylogenetic uncertainty, different levels of species delineation, and different assumed amounts of unsampled diversity resulting in an incomplete phylogeny. Overall, our results are consistent with a "jack-of-all-trades" tradeoff where generalists suffer a cost in any individual environment, resulting in rapid evolution of niche specialists and shed light on how bacteria could transition between biomes.


Asunto(s)
Evolución Biológica , Myxococcales , Myxococcales/genética , Ecosistema , Filogenia , Especiación Genética
9.
PeerJ ; 12: e17176, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38560479

RESUMEN

The effects of nitrogen application or earthworms on soil respiration in the Huang-Huai-Hai Plain of China have received increasing attention. However, the response of soil carbon dioxide (CO2) emission to nitrogen application and earthworm addition is still unclear. A field experiment with nitrogen application frequency and earthworm addition was conducted in the Huang-Huai-Hai Plain. Results showed nitrogen application frequency had a significant effect on soil respiration, but neither earthworms nor their interaction with nitrogen application frequency were significant. Low-frequency nitrogen application (NL) significantly increased soil respiration by 25%, while high-frequency nitrogen application (NH), earthworm addition (E), earthworm and high-frequency nitrogen application (E*NH), and earthworm and low-frequency nitrogen application (E*NL) also increased soil respiration by 21%, 21%, 12%, and 11%, respectively. The main reason for the rise in soil respiration was alterations in the bacterial richness and keystone taxa (Myxococcales). The NH resulted in higher soil nitrogen levels compared to NL, but NL had the highest bacterial richness. The abundance of Corynebacteriales and Gammaproteobacteria were positively connected with the CO2 emissions, while Myxococcales, Thermoleophilia, and Verrucomicrobia were negatively correlated. Our findings indicate the ecological importance of bacterial communities in regulating the carbon cycle in the Huang-Huai-Hai Plain.


Asunto(s)
Myxococcales , Oligoquetos , Animales , Dióxido de Carbono , Glycine max , Nitrógeno/farmacología , Suelo , Productos Agrícolas
10.
J Appl Microbiol ; 135(5)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38649930

RESUMEN

AIM: Corallococcus species are diverse in the natural environment with 10 new Corallococcus species having been characterized in just the last 5 years. As well as being an abundant myxobacterial genus, they produce several secondary metabolites, including Corallopyronin, Corramycin, Coralmycin, and Corallorazine. We isolated a novel strain Corallococcus spp RDP092CA from soil in South Wales, UK, using Candida albicans as prey bait and characterized its predatory activities against pathogenic bacteria and yeast. METHODS AND RESULTS: The size of the RDP092CA genome was 8.5 Mb with a G + C content of 71.4%. Phylogenetically, RDP092CA is closely related to Corallococcus interemptor, C. coralloides, and C. exiguus. However, genome average nucleotide identity and digital DNA-DNA hybridization values are lower than 95% and 70% when compared to those type strains, implying that it belongs to a novel species. The RDP092CA genome harbours seven types of biosynthetic gene clusters (BGCs) and 152 predicted antimicrobial peptides. In predation assays, RDP092CA showed good predatory activity against Escherichia coli, Pseudomonas aeruginosa, Citrobacter freundii, and Staphylococcus aureus but not against Enterococcus faecalis. It also showed good antibiofilm activity against all five bacteria in biofilm assays. Antifungal activity against eight Candida spp. was variable, with particularly good activity against Meyerozyma guillermondii DSM 6381. Antimicrobial peptide RDP092CA_120 exhibited potent antibiofilm activity with >50% inhibition and >60% dispersion of biofilms at concentrations down to 1 µg/ml. CONCLUSIONS: We propose that strain RDP092CA represents a novel species with promising antimicrobial activities, Corallococcus senghenyddensis sp. nov. (=NBRC 116490T =CCOS 2109T), based on morphological, biochemical, and genomic features.


Asunto(s)
Myxococcales , Filogenia , Myxococcales/genética , Myxococcales/metabolismo , Myxococcales/aislamiento & purificación , Composición de Base , Genoma Bacteriano , Microbiología del Suelo , Antiinfecciosos/farmacología , Pruebas de Sensibilidad Microbiana , Candida albicans/efectos de los fármacos , Familia de Multigenes , ADN Bacteriano/genética , ARN Ribosómico 16S/genética
11.
J Biosci Bioeng ; 137(5): 354-359, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38458885

RESUMEN

Myxobacteria have comparatively large genomes that contain many biosynthetic genes with the potential to produce secondary metabolites. Based on genome mining, we discovered a new biosynthetic gene cluster of class III lanthipeptide in the genome of the myxobacterium Melittangium boletus. The biosynthetic gene cluster contained a precursor peptide-coding gene bolA, and a class III lanthipeptide synthetase-coding gene bolKC. The expression vector containing bolA and bolKC was constructed using synthetic DNA with codon-optimized sequences based on the commercially available vector pET29b. Co-expression of the two genes in the host Escherichia coli BL21(DE3) yielded a new class III lanthipeptide named boletupeptin. The structure of boletupeptin was proposed to have one unit of labionin, as determined by mass spectrometry experiments after reductive cleavage. This is the first report of a class III lanthipeptide from a myxobacterial origin.


Asunto(s)
Myxococcales , Myxococcales/genética , Myxococcales/metabolismo , Péptidos/metabolismo , Familia de Multigenes/genética
12.
Nature ; 628(8008): 657-663, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38509367

RESUMEN

In response to pathogen infection, gasdermin (GSDM) proteins form membrane pores that induce a host cell death process called pyroptosis1-3. Studies of human and mouse GSDM pores have revealed the functions and architectures of assemblies comprising 24 to 33 protomers4-9, but the mechanism and evolutionary origin of membrane targeting and GSDM pore formation remain unknown. Here we determine a structure of a bacterial GSDM (bGSDM) pore and define a conserved mechanism of pore assembly. Engineering a panel of bGSDMs for site-specific proteolytic activation, we demonstrate that diverse bGSDMs form distinct pore sizes that range from smaller mammalian-like assemblies to exceptionally large pores containing more than 50 protomers. We determine a cryo-electron microscopy structure of a Vitiosangium bGSDM in an active 'slinky'-like oligomeric conformation and analyse bGSDM pores in a native lipid environment to create an atomic-level model of a full 52-mer bGSDM pore. Combining our structural analysis with molecular dynamics simulations and cellular assays, our results support a stepwise model of GSDM pore assembly and suggest that a covalently bound palmitoyl can leave a hydrophobic sheath and insert into the membrane before formation of the membrane-spanning ß-strand regions. These results reveal the diversity of GSDM pores found in nature and explain the function of an ancient post-translational modification in enabling programmed host cell death.


Asunto(s)
Gasderminas , Myxococcales , Microscopía por Crioelectrón , Gasderminas/química , Gasderminas/metabolismo , Gasderminas/ultraestructura , Interacciones Hidrofóbicas e Hidrofílicas , Lípidos de la Membrana/química , Lípidos de la Membrana/metabolismo , Simulación de Dinámica Molecular , Myxococcales/química , Myxococcales/citología , Myxococcales/ultraestructura , Estructura Cuaternaria de Proteína , Subunidades de Proteína/química , Subunidades de Proteína/metabolismo , Proteolisis , Piroptosis
13.
Microbiol Spectr ; 12(3): e0368923, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38298128

RESUMEN

In the past century, microbial natural products have proven themselves to be substantial and fruitful sources of anti-infectives. In addition to the well-studied Actinobacteria, understudied bacterial taxa like the Gram-negative myxobacteria have increasingly gained attention in the ongoing search for novel and biologically active natural products. In the course of a regional sampling campaign to source novel myxobacteria, we recently uncovered new myxobacterial strains MCy12716 and MCy12733 belonging to the Myxococcaceae clade. Early bioactivity screens of the bacterial extracts revealed the presence of bioactive natural products that were identified as angiolam A and several novel derivatives. Sequencing of the corresponding producer strains allowed the identification of the angiolam biosynthetic gene cluster, which was verified by targeted gene inactivation. Based on bioinformatic analysis of the biosynthetic gene cluster, a concise biosynthesis model was devised to explain angiolam biosynthesis. Importantly, novel angiolam derivatives uncovered in this study named angiolams B, C, and D were found to display promising antiparasitic activities against the malaria pathogen Plasmodium falciparum in the 0.3-0.8 µM range.IMPORTANCEThe COVID-19 pandemic and continuously emerging antimicrobial resistance (AMR) have recently raised awareness about limited treatment options against infectious diseases. However, the shortage of treatment options against protozoal parasitic infections, like malaria, is much more severe, especially for the treatment of so-called neglected tropical diseases. The detection of anti-parasitic bioactivities of angiolams produced by MCy12716 and MCy12733 displays the hidden potential of scarcely studied natural products to have promising biological activities in understudied indications. Furthermore, the improved biological activities of novel angiolam derivatives against Plasmodium falciparum and the evaluation of its biosynthesis display the opportunities of the angiolam scaffold on route to treat protozoal parasitic infections as well as possible ways to increase the production of derivatives with improved bioactivities.


Asunto(s)
Productos Biológicos , Malaria Falciparum , Myxococcales , Humanos , Myxococcales/genética , Antiparasitarios/farmacología , Pandemias , Plasmodium falciparum , Productos Biológicos/farmacología
14.
Artículo en Inglés | MEDLINE | ID: mdl-38323900

RESUMEN

Three microaerophilic bacterial strains, designated SG22T, SG63T and SG29T were isolated from paddy soils in PR China. Cells of these strains were Gram-staining-negative and long rod-shaped. SG22T, SG63T and SG29T showed the highest 16S rRNA gene sequence similarities with the members of the genus Anaeromyxobacter. The results of phylogenetic and phylogenomic analysis also indicated that these strains clustered with members of the genus Anaeromyxobacter. The main respiratory menaquinone of SG22T, SG63T and SG29T was MK-8 and the major fatty acids were iso-C15 : 0, iso-C17 : 0 and C16 : 0. SG22T, SG29T and SG63T not only possessed iron reduction ability but also harboured genes (nifHDK) encoding nitrogenase. The genomic DNA G+C contents of SG22T, SG63T and SG29T ranged from 73.3 to 73.5 %. The average nucleotide identity (ANI) and digital DNA-DNA hybridisation (dDDH) values between SG22T, SG63T and SG29T and the closely related species of the genus Anaeromyxobacter were lower than the cut-off values (dDDH 70 % and ANI 95-96 %) for prokaryotic species delineation. On the basis of these results, strains SG22T, SG63T and SG29T represent three novel species within the genus Anaeromyxobacter, for which the names Anaeromyxobacter terrae sp. nov., Anaeromyxobacter oryzisoli sp. nov. and Anaeromyxobacter soli sp. nov., are proposed. The type strains are SG22T (= GDMCC 1.3185T = JCM 35581T), SG63T (= GDMCC 1.2914T = JCM 35124T) and SG29T (= GDMCC 1.2911T = JCM 35123T).


Asunto(s)
Myxococcales , Bacterias Fijadoras de Nitrógeno , Compuestos Férricos , Filogenia , ARN Ribosómico 16S/genética , Composición de Base , Ácidos Grasos/química , Análisis de Secuencia de ADN , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana , Nucleótidos , Suelo
15.
Nat Prod Rep ; 41(6): 905-934, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38390645

RESUMEN

Covering: 2017.01 to 2023.11Natural products biosynthesized by myxobacteria are appealing due to their sophisticated chemical skeletons, remarkable biological activities, and intriguing biosynthetic enzymology. This review aims to systematically summarize the advances in the discovery methods, new structures, and bioactivities of myxobacterial NPs reported in the period of 2017-2023. In addition, the peculiar biosynthetic pathways of several structural families are also highlighted.


Asunto(s)
Productos Biológicos , Myxococcales , Productos Biológicos/metabolismo , Productos Biológicos/química , Myxococcales/metabolismo , Myxococcales/química , Estructura Molecular , Vías Biosintéticas , Descubrimiento de Drogas
16.
Science ; 383(6682): 512-519, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38301007

RESUMEN

The generation of cyclic oligoadenylates and subsequent allosteric activation of proteins that carry sensory domains is a distinctive feature of type III CRISPR-Cas systems. In this work, we characterize a set of associated genes of a type III-B system from Haliangium ochraceum that contains two caspase-like proteases, SAVED-CHAT and PCaspase (prokaryotic caspase), co-opted from a cyclic oligonucleotide-based antiphage signaling system (CBASS). Cyclic tri-adenosine monophosphate (AMP)-induced oligomerization of SAVED-CHAT activates proteolytic activity of the CHAT domains, which specifically cleave and activate PCaspase. Subsequently, activated PCaspase cleaves a multitude of proteins, which results in a strong interference phenotype in vivo in Escherichia coli. Taken together, our findings reveal how a CRISPR-Cas-based detection of a target RNA triggers a cascade of caspase-associated proteolytic activities.


Asunto(s)
Proteínas Bacterianas , Proteínas Asociadas a CRISPR , Sistemas CRISPR-Cas , Caspasas , Myxococcales , Proteolisis , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Caspasas/química , Caspasas/genética , Proteínas Asociadas a CRISPR/genética , Proteínas Asociadas a CRISPR/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , ARN/metabolismo , Myxococcales/enzimología , Myxococcales/genética , Dominios Proteicos
17.
Appl Microbiol Biotechnol ; 108(1): 122, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38229328

RESUMEN

The myxobacteria are an attractive bioresource for bioactive compounds since the large size genome contains many biosynthetic gene clusters of secondary metabolites. The genome of the myxobacterium Melittangium boletus contains three biosynthetic gene clusters for lanthipeptide production. One of the gene clusters includes genes coding lanthipeptide precursor (melA), class II lanthipeptide synthetase (melM), and transporter (melT). The amino acid sequence of melA indicated similarity with that of known lanthipeptides mersacidin and lichenicidin A1 by the alignment. To perform heterologous production of new lanthipeptides, the expression vector containing the essential genes (melA and melM) was constructed by utilizing codon-optimized synthetic genes. The co-expression of two genes in the host bacterial cells of Escherichia coli BL21 (DE3) afforded new lanthipeptides named melittapeptins A-C. The structures of melittapeptins A-C including lanthionine/methyllanthionine bridge pattern were proposed based on protease digestion and MS/MS experiments. The native strain of M. boletus did not produce melittapeptins A-C, so heterologous production using the biosynthetic gene cluster was effective in obtaining the lanthipeptides. Melittapeptins A-C showed specific and potent antibacterial activity to the Gram-positive bacterium Micrococcus luteus. To the best of our knowledge, this is the first report of antibacterial lanthipeptides derived from myxobacterial origin. KEY POINTS: • New lanthipeptides melittapeptins were heterologously produced in Escherichia coli. • Melittapeptins showed specific antibacterial activity against Micrococcus luteus. • Melittapeptins were the first antibacterial lanthipeptides of myxobacterial origin.


Asunto(s)
Bacteriocinas , Myxococcales , Espectrometría de Masas en Tándem , Bacteriocinas/genética , Bacteriocinas/farmacología , Secuencia de Aminoácidos , Antibacterianos/metabolismo , Myxococcales/genética , Myxococcales/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo
18.
Int. microbiol ; 12(1): 23-28, mar. 2009. tab, graf, ilus
Artículo en Inglés | IBECS | ID: ibc-72361

RESUMEN

Uptake hydrogenase is an enzyme that is beneficial for nitrogen fixation in bacteria. Recent studies have shown that Frankia sp. has two sets of uptake hydrogenase genes, organized in synton 1 and synton 2. In the present study, phylogenetic analysis of the structural subunits of hydrogenase syntons 1 and 2 showed a distinct clustering pattern between the proteins of Frankia strains that were isolated from different host plants and non-Frankia organisms. The structural subunits of hydrogenase synton 1 of Frankia sp. CpI1, Frankia alni ACN14a, and F. alni AvCI1 were grouped together while those of Frankia spp. CcI3, KB5, UGL140104, and UGL011102 formed another group. The structural subunits of hydrogenase synton 2 of F. alni ACN14a and Frankia spp. CcI3 and BCU110501 grouped together, but those of Frankia spp. KB5 and CpI1, F. alni ArI3, and F. alniAvCI1 comprised a separate group. The structural subunits of hydrogenase syntons 1 and 2 of Frankia sp. EAN1pec were more closely related to those of non-Frankia bacteria, i.e., Streptomyces avermitilis and Anaeromyxobacter sp., respectively, than to those of other Frankia strains, suggesting the occurrence of lateral gene transfer between these organisms. In addition, the accessory Hyp proteins of hydrogenase syntons 1 and 2 of F. alni ACN14a and Frankia sp. CcI3 were shown to be phylogenetically more related to each other than to those of Frankia EAN1pec (AU)


No disponible


Asunto(s)
Hidrogenasas/síntesis química , Bacterias/genética , Filogenia , Streptomyces/genética , Myxococcales/genética
19.
Chinese Journal of Biotechnology ; (12): 511-515, 2003.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-259157

RESUMEN

Novel macrolides epothilones, produced by cellulolytic myxobacterium Sorangium cellulosum, have the activity to promote microtubule assembly, and are considered to be a potential successor to the famous antitumor drug taxol. The biosynthetic genes leading to the epothilones are clustered into a large operon. The multi-enzyme complex is a hetero-gene cluster of polyketide synthase (PKS) and non-ribosomal peptide synthetases (NRPS) and contains several functional modules, i.e. a loading module, one NRPS module, eight PKS modules, and a P450 epoxidase. The former ten modules biosynthesize desoxyepothilone (epothilones C and D), which is then epoxidized at C12 and C13 and converted into epothilones (epothilones A and B) by the P450 epoxidase. The NRPS module is responsible for the formation of the thiazole side chain from cysteine. The biosynthesis procedure of epothilones can be divided into 5 stages, i.e. formation of holo-ACP/PCP, chain initiation and thiazole ring formation, chain elongation, termination and epoxidation, and post-modification. The analysis of the gene cluster and the biosynthetic pathway reveals that novel epothilone analogs could not only be produced by chemical synthesis/modification, tranditional microbial technologies, but also can be genetically manipulated through combinatiorial biosynthesis approaches.


Asunto(s)
Proteínas Bacterianas , Genética , Metabolismo , Epotilonas , Química , Metabolismo , Estructura Molecular , Familia de Multigenes , Genética , Fisiología , Myxococcales , Genética , Metabolismo , Péptido Sintasas , Genética , Metabolismo , Sintasas Poliquetidas , Genética , Metabolismo
20.
Rev. Inst. Invest. Cienc. Salud ; 4(1): 123-32, jul. 1989. ilus
Artículo en Español | LILACS | ID: lil-91973

RESUMEN

Realizamos un estudio detallado de la especie bacteriana Mixococcus xanthus, perteneciente al Orden Mixobacteriales, con la finalidad de estudiar sus cambios morfológicos y características bacteriolíticas. Pudimos obtener cultivos puros, lo que nos facilitó el estudio de su ciclo vital. Observamos sus características culturales y morfológicas, seguimos por hora su poliformismo, hasta la observación de microcistos. Comprobamos que la bacteria de nuestro estudio era bacteriolítica, siendo capaz de lisar colonias bacterianas tanto de bacterias gram positivas como gram negativas, lo que nos indica su capacidad de formar sustancias antimicrobianas


Asunto(s)
Myxococcales/citología , Myxococcales/clasificación , Myxococcales/aislamiento & purificación , Polimorfismo Genético
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