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1.
Syst Appl Microbiol ; 43(1): 126051, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892483

RESUMO

A polyphasic study was undertaken to establish the taxonomic status of three Modestobacter strains isolated from a high altitude Atacama Desert soil. The isolates, strains 1G6T, 1G14 and 1G50, showed chemotaxonomic and morphological properties characteristic of members of the genus Modestobacter. The peptidoglycan contained meso-diaminopimelic acid, the whole cell sugars were glucose and ribose (diagnostic sugars) and arabinose, the predominant menaquinone was MK-9(H4), polar lipid patterns contained diphosphatidylglycerol, glycophosphatidylinositol, phosphatidylethanolamine (diagnostic component), phosphatidylglycerol and phosphatidylinositol while whole cellular fatty acid profiles consisted of complex mixtures of saturated, unsaturated iso- and anteiso-components. The isolates were shown to have different BOX-PCR fingerprint and physiological profiles. They formed a distinct phyletic line in Modestobacter 16S rRNA gene trees, were most closely related to the type strain of Modestobacter italicus (99.9 % similarity) but were distinguished from this and other closely related Modestobacter type strains using a combination of phenotypic properties. Average nucleotide identity and digital DNA:DNA hybridization similarities between the draft genome sequences of isolate 1G6T and M. italicus BC 501T were 90.9 % and 42.3 %, respectively, indicating that they belong to different species. Based on these phenotypic and genotypic data it is proposed that the isolates be assigned to a novel species in the genus Modestobacter, namely as Modestobacter excelsi with isolate 1G6T (=DSM 107535T =PCM 3004T) as the type strain. Analysis of the whole genome sequence of M. excelsi 1G6T (genome size of 5.26 Mb) showed the presence of genes and gene clusters that encode for properties that are in tune with its adaptation to extreme environmental conditions that prevail in the Atacama Desert biome.


Assuntos
Actinobacteria/classificação , Actinobacteria/fisiologia , Clima Desértico , Microbiologia do Solo , Actinobacteria/química , Actinobacteria/citologia , Altitude , DNA Bacteriano/genética , Ácidos Graxos/análise , Genoma Bacteriano/genética , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Especificidade da Espécie , Estresse Fisiológico/genética , Vitamina K 2/química
2.
J Agric Food Chem ; 68(1): 17-32, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31809036

RESUMO

Weeds had caused significant loss for crop production in the process of agriculture. Herbicides have played an important role in securing crop production. However, the high reliance on herbicides has led to environmental issues as well as the evolution of herbicide resistance. Thus, there is an urgent need for new herbicides with safer toxicological profiles and novel modes of action. Actinomycetes produce very diverse bioactive compounds, of which some show potent biopesticidal activity. The herbicidal secondary metabolites from actinomycetes can be classified into several groups, such as amino acids, peptides, nucleosides, macrolides, lactones, amide, amines, etc., some of which have been successfully developed as commercial herbicides. The structure diversity and evolved biological activity of secondary metabolites from actinomycetes can offer opportunities for the development of both directly used bioherbicides and synthetic herbicides with new target sites, and thus, this review focuses on the structure, herbicidal activity, and modes of action of secondary metabolites from actinomycetes.


Assuntos
Actinobacteria/química , Herbicidas/química , Herbicidas/farmacologia , Actinobacteria/metabolismo , Descoberta de Drogas , Herbicidas/metabolismo , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/crescimento & desenvolvimento , Metabolismo Secundário , Controle de Plantas Daninhas
3.
Curr Top Med Chem ; 19(31): 2868-2918, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31724505

RESUMO

Actinomycetes is an abundant resource for discovering a large number of lead compounds, which play an important role in microbial drug discovery. Compared to terrestrial microorganisms, marine actinomycetes have unique metabolic pathways because of their special living environment, which has the potential to produce a variety of bioactive substances. In this paper, secondary metabolites isolated from marine actinomycetes are reviewed (2013-2018), most of which exhibited cytotoxic, antibacterial, and antiviral biological activities.


Assuntos
Actinobacteria/química , Antibacterianos/metabolismo , Antineoplásicos/metabolismo , Antivirais/metabolismo , Produtos Biológicos/metabolismo , Actinobacteria/metabolismo , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antivirais/química , Antivirais/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Humanos
4.
Molecules ; 24(20)2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31614954

RESUMO

Abstract: Apple tree canker infected by Valsa mali var. mali is a serious and widely distributed disease in China. Saccharothrix yanglingensis Hhs.015 is an endophytic actinomycete isolated from cucumber roots, and it has been proven that this strain is a promising biocontrol agent on apple tree canker in previous studies. The aim of this study was to elucidate the active ingredients in its metabolites. Two pentaene macrolides, WH01 and WH02, were isolated from strain Hhs.015, and their structures were elucidated based on the extensive spectroscopic analysis. WH01 and WH02 were identified as fungichromin and 1'-deoxyfungichromin, among which WH02 is a novel compound. These two compounds showed strong in vitro and in vivo antifungal activity against V. mali. By comparison of the structures of hyphae cells treated by pure compound and fermentation broth, it has been proven that pentaene macrolides are the main active ingredients in the metabolites of strain Hhs.015. This is the first report on the antifungal activity of fungichromin and its analogs on V. mali, and the 28-member pentaene macrolides were also firstly isolated from the genus of Saccharothrix.


Assuntos
Actinobacteria/química , Antifúngicos/química , Cucumis sativus/química , Doenças das Plantas/prevenção & controle , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , China , Fermentação , Hifas/efeitos dos fármacos , Malus/efeitos dos fármacos , Malus/microbiologia , Raízes de Plantas
5.
Nature ; 576(7786): 321-325, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31597161

RESUMO

Host infection by pathogenic mycobacteria, such as Mycobacterium tuberculosis, is facilitated by virulence factors that are secreted by type VII secretion systems1. A molecular understanding of the type VII secretion mechanism has been hampered owing to a lack of three-dimensional structures of the fully assembled secretion apparatus. Here we report the cryo-electron microscopy structure of a membrane-embedded core complex of the ESX-3/type VII secretion system from Mycobacterium smegmatis. The core of the ESX-3 secretion machine consists of four protein components-EccB3, EccC3, EccD3 and EccE3, in a 1:1:2:1 stoichiometry-which form two identical protomers. The EccC3 coupling protein comprises a flexible array of four ATPase domains, which are linked to the membrane through a stalk domain. The domain of unknown function (DUF) adjacent to the stalk is identified as an ATPase domain that is essential for secretion. EccB3 is predominantly periplasmatic, but a small segment crosses the membrane and contacts the stalk domain. This suggests that conformational changes in the stalk domain-triggered by substrate binding at the distal end of EccC3 and subsequent ATP hydrolysis in the DUF-could be coupled to substrate secretion to the periplasm. Our results reveal that the architecture of type VII secretion systems differs markedly from that of other known secretion machines2, and provide a structural understanding of these systems that will be useful for the design of antimicrobial strategies that target bacterial virulence.


Assuntos
Microscopia Crioeletrônica , Mycobacterium smegmatis/química , Sistemas de Secreção Tipo VII/química , Sistemas de Secreção Tipo VII/ultraestrutura , Actinobacteria/química , Actinobacteria/enzimologia , Adenosina Trifosfatases/química , Adenosina Trifosfatases/isolamento & purificação , Adenosina Trifosfatases/ultraestrutura , Trifosfato de Adenosina/metabolismo , Modelos Moleculares , Mycobacterium smegmatis/enzimologia , Mycobacterium smegmatis/ultraestrutura , Domínios Proteicos , Estrutura Quaternária de Proteína , Subunidades Proteicas/química , Subunidades Proteicas/isolamento & purificação , Relação Estrutura-Atividade , Sistemas de Secreção Tipo VII/isolamento & purificação
6.
Int J Mol Sci ; 20(16)2019 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-31405215

RESUMO

In family GH13 of the carbohydrate-active enzyme database, subfamily 18 contains glycoside phosphorylases that act on α-sugars and glucosides. Because their phosphorolysis reactions are effectively reversible, these enzymes are of interest for the biocatalytic synthesis of various glycosidic compounds. Sucrose 6F-phosphate phosphorylases (SPPs) constitute one of the known substrate specificities. Here, we report the characterization of an SPP from Ilumatobacter coccineus with a far stricter specificity than the previously described promiscuous SPP from Thermoanaerobacterium thermosaccharolyticum. Crystal structures of both SPPs were determined to provide insight into their similarities and differences. The residues responsible for binding the fructose 6-phosphate group in subsite +1 were found to differ considerably between the two enzymes. Furthermore, several variants that introduce a higher degree of substrate promiscuity in the strict SPP from I. coccineus were designed. These results contribute to an expanded structural knowledge of enzymes in subfamily GH13_18 and facilitate their rational engineering.


Assuntos
Actinobacteria/enzimologia , Fosforilases/metabolismo , Sacarose/metabolismo , Thermoanaerobacterium/enzimologia , Actinobacteria/química , Actinobacteria/metabolismo , Cristalografia por Raios X , Modelos Moleculares , Fosforilases/química , Conformação Proteica , Especificidade por Substrato , Thermoanaerobacterium/química , Thermoanaerobacterium/metabolismo
7.
Syst Appl Microbiol ; 42(5): 126004, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31402073

RESUMO

Two novel strains, designated 11W25H-1T and 8H24J-4-2T, were isolated from surface-sterilized plant tissues collected from the Taklamakan Desert in the Xinjiang Uygur Autonomous Region, China. The strains were characterized by a polyphasic approach in order to clarify their taxonomic positions. They were Gram-stain positive, aerobic, non-motile, non-spore-forming and rod-shaped. The 16S rRNA gene sequences of the strains showed highest similarities with Labedella gwakjiensis KCTC 19176T (99.2% and 98.9%, respectively) and Labedella endophytica CPCC 203961T (98.9% and 99.0%, respectively). The sequence similarity between strains 11W25H-1T and 8H24J-4-2T was 99.4%. Phylogenetic analyses based on 16S rRNA gene sequences and single-copy phylogenetic marker genes (pMGs) showed that the two strains belonged to the genus Labedella and formed a separate cluster from the closest species L. gwakjiensis KCTC 19176T and L. endophytica CPCC 203961T. Genomic analyses, including average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH), clearly separated the strains from each other and from the other species of the genus Labedella with values below the thresholds for species delineation. The two strains showed chemotaxonomic characteristics and phenotypic properties in agreement with the description of the genus Labedella and also confirmed the differentiation from the closest species. The data demonstrated that strains 11W25H-1T and 8H24J-4-2T represented two novel species of the genus Labedella, for which the names Labedella phragmitis sp. nov. (type strain 11W25H-1T=JCM 33144T=CGMCC 1.16700T) and Labedella populi sp. nov. (type strain 8H24J-4-2T=JCM 33143T=CGMCC 1.16697T) are proposed.


Assuntos
Actinobacteria/classificação , Filogenia , Plantas/microbiologia , Actinobacteria/química , Actinobacteria/genética , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Genes Bacterianos/genética , Genoma Bacteriano/genética , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Especificidade da Espécie , Vitamina K 2/química
8.
Biochim Biophys Acta Bioenerg ; 1860(10): 148033, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31226315

RESUMO

Respiration in aerobic Actinobacteria involves a cytochrome bc1-aa3 supercomplex with a diheme cytochrome c1, first isolated from Corynebacterium glutamicum. Synthesis of a functional cytochrome c oxidase requires incorporation of CuA, CuB, heme a, and heme a3. In contrast to eukaryotes and α-proteobacteria, this process is poorly understood in Actinobacteria. Here, we analyzed the role of a Surf1 homolog of C. glutamicum in the formation of a functional bc1-aa3 supercomplex. Deletion of the surf1 gene (cg2460) in C. glutamicum caused a growth defect and cytochrome spectra revealed reduced levels of cytochrome c and a and an increased level of cytochrome d. Membranes of the Δsurf1 strain had lost the ability to oxidize the artificial electron donor N,N,N',N'-tetramethyl-p-phenylenediamine, suggesting that Surf1 is essential for the formation of a functional cytochrome aa3 oxidase. In contrast to the wild type, a bc1-aa3 supercomplex could not be purified from solubilized membranes of the Δsurf1 mutant. A transcriptome comparison revealed that the genes of the SigC regulon including those for cytochrome bd oxidase were upregulated in the Δsurf1 strain as well as the copper deprivation-inducible gene ctiP. Complementation studies showed that the Surf1 homologs of Corynebacterium diphtheriae, Mycobacterium smegmatis and Mycobacterium tuberculosis could at least partially abolish the growth defect of the C. glutamicum Δsurf1 mutant, suggesting that Surf1 is a conserved assembly factor for actinobacterial cytochrome aa3 oxidase.


Assuntos
Actinobacteria/química , Complexo IV da Cadeia de Transporte de Elétrons/biossíntese , Proteínas de Membrana/fisiologia , Proteínas Mitocondriais/fisiologia , Proteínas de Bactérias , Corynebacterium glutamicum/química , Grupo dos Citocromos c , Citocromos c1 , Complexo III da Cadeia de Transporte de Elétrons , Oxirredutases/fisiologia
9.
ACS Chem Biol ; 14(7): 1619-1627, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31188556

RESUMO

Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) with a unique 3D-interlocked structure, in which an N-terminal macrolactam ring is threaded by a linear C-terminal part. The unique structure of lasso peptides is introduced into ribosomally translated precursor peptides by lasso peptide synthetase encompassing proteins B and C or B1, B2, and C when the B enzyme is split into two distinct proteins. The B1 protein recognizes the leader sequence of the precursor peptide, and then the B2 protein cleaves it. The C protein catalyzes the formation of the macrolactam ring. However, the detailed mechanism of lasso peptide maturation has remained elusive, due to the lack of structural information about the responsible proteins. Here we report the crystal structure of the B1 protein from the thermophilic actinobacteria, Thermobifida fusca (TfuB1), complexed with the leader peptide (TfuA-Leader), which revealed the detailed mechanism of leader peptide recognition. The structure of TfuB1 consists of an N-terminal ß-sheet and three C-terminal helices. The leader peptide is docked on one edge of the N-terminal ß-sheet of TfuB1, as an additional ß strand. Three conserved amino acid residues of the leader peptide (TfuA Tyr-17, Pro-14, and Leu-12) fit well on the hydrophobic cleft between the ß-sheet and adjacent helices. Biochemical analysis demonstrated that these conserved residues are essential for affinity between TfuB1 and the TfuA-Leader. Furthermore, we found that TfuB1 and the leader peptide jointly form a hydrophobic patch on the ß-sheet, which includes the highly conserved TfuA Phe-6 and TfuB1 Tyr33. Homology modeling and mutational analysis of the B1 protein from a firmicute, Bacillus pseudomycoides (PsmB1), revealed that the hydrophobic patch is conserved in a wide range of species and involved in the cleavage activity of the B2 protein, indicating it forms the interaction surface for the B2 protein or the core part of the precursor peptide.


Assuntos
Actinobacteria/química , Proteínas de Bactérias/química , Peptídeos/química , Sinais Direcionadores de Proteínas , Cristalografia por Raios X , Modelos Moleculares , Biossíntese Peptídica , Conformação Proteica , Processamento de Proteína Pós-Traducional
10.
Antonie Van Leeuwenhoek ; 112(11): 1611-1621, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31222464

RESUMO

A Gram-stain positive, aerobic, rod-shaped bacterium, designated strain NEAU-85T, was isolated from rhizosphere soil of lettuce and characterised using a polyphasic approach. Strain NEAU-85T was found to be catalase positive, motile and able to grow at between 10 and 30 °C. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain NEAU-85T belongs to the genus Cryobacterium and is closely related to the type strain Cryobacterium psychrotolerans JCM 13925T (98.5%) and also to Leifsonia kafniensis NCCB 100216T (97.6%). Multilocus sequence analysis using the concatenated gene sequences of the atpD, dnaK, recA, rpoB, sevY and ychF genes showed that strain NEAU-85T belongs to the genus Cryobacterium. The digital DNA-DNA hybridization values revealed that strain NEAU-85T is distinct from its close phylogenetic neighbour C. psychrotolerans. The menaquinones were identified as MK-10 and MK-11. The phospholipid profile was found to consist of diphosphatidylglycerol, phosphatidylglycerol, phospholipid, an unidentified glycolipid and an unidentified lipid. The major fatty acids were identified as anteiso-C15:0, anteiso-C15:1 and iso-C16:0. The genomic DNA G + C content of strain NEAU-85T was determined to be 68.9 mol%. The DNA-DNA hybridization value between them was less than 70%. On the basis of phenotypic, genotypic and phylogenetic data, strain NEAU-85T can be concluded to represent a novel species of the genus Cryobacterium, for which the name Cryobacterium tepidiphilum sp. nov. is proposed. The type strain is NEAU-85T (= CCTCC AA 2018035T = JCM 32545T).


Assuntos
Actinobacteria/classificação , Actinobacteria/isolamento & purificação , Alface/microbiologia , Rizosfera , Microbiologia do Solo , Actinobacteria/química , Actinobacteria/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , Genoma Bacteriano , Tipagem de Sequências Multilocus , Fenótipo , Filogenia , RNA Ribossômico 16S/genética
11.
Mar Drugs ; 17(5)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31035452

RESUMO

Rare actinomycetes are prolific in the marine environment; however, knowledge about their diversity, distribution and biochemistry is limited. Marine rare actinomycetes represent a rather untapped source of chemically diverse secondary metabolites and novel bioactive compounds. In this review, we aim to summarize the present knowledge on the isolation, diversity, distribution and natural product discovery of marine rare actinomycetes reported from mid-2013 to 2017. A total of 97 new species, representing 9 novel genera and belonging to 27 families of marine rare actinomycetes have been reported, with the highest numbers of novel isolates from the families Pseudonocardiaceae, Demequinaceae, Micromonosporaceae and Nocardioidaceae. Additionally, this study reviewed 167 new bioactive compounds produced by 58 different rare actinomycete species representing 24 genera. Most of the compounds produced by the marine rare actinomycetes present antibacterial, antifungal, antiparasitic, anticancer or antimalarial activities. The highest numbers of natural products were derived from the genera Nocardiopsis, Micromonospora, Salinispora and Pseudonocardia. Members of the genus Micromonospora were revealed to be the richest source of chemically diverse and unique bioactive natural products.


Assuntos
Actinobacteria/química , Organismos Aquáticos/química , Produtos Biológicos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Antimaláricos/química , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antiparasitários/química , Antiparasitários/isolamento & purificação , Antiparasitários/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação
12.
Int Microbiol ; 22(4): 521-530, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31144066

RESUMO

A total of 168 actinomycete colonies were isolated from 14 sediment samples of the northern parts of the Oman Sea and were screened for cytotoxic and antimicrobial activity. Among four media and two treatments, the glucose arginine agar medium (18%) and heat treatment (28.3%) showed maximum isolation rate of actinomycetes. Preliminary characterization revealed that the members of Streptomycetaceae were widely distributed (66%) in the most of the sampling stations followed by Micromonosporaceae (14%), Nocardiaceae (6%), and Pseudonocardiaceae (4%), respectively. Approximately, 23.8% of the isolates inhibited the growth of at least one of the microbial test strains, while the majority of them belonged to the Streptomycetaceae family. Minimum inhibitory concentrations of the ethyl acetate culture extracts of the five most putative isolates varied from 64 µg/mL against Micrococcus luteus and Candida albicans to 1 mg/mL against Aspergillus niger. These extracts showed significant cytotoxic activity at18.74-193.5 µg/mL on the human breast (MCF7), colon (HCT 116), and liver (HepG2) tumor cell lines while exhibited less or no cytotoxicity on the normal cell line (HUVEC). Interestingly, IFSRI 193 extract selectively inhibited the growth of HCT 116 cell line and gram-positive bacteria. 16S rRNA gene sequencing revealed that the potent isolates have 97 to 99% similarity with S. chartreusis, S. cacaoi, S. sampsonii, S. qinglanensis, and S. diastaticus. These results suggested that the five Streptomyces strains could be considered candidates for discovering the antitumor antibiotics.


Assuntos
Actinobacteria/química , Anti-Infecciosos/farmacologia , Sedimentos Geológicos/microbiologia , Actinobacteria/classificação , Actinobacteria/genética , Actinobacteria/metabolismo , Anti-Infecciosos/química , Anti-Infecciosos/metabolismo , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , DNA Bacteriano/genética , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Micrococcus luteus/crescimento & desenvolvimento , Omã , Filogenia , RNA Ribossômico 16S/genética , Água do Mar/microbiologia
13.
Prog Chem Org Nat Prod ; 108: 207-296, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30924015

RESUMO

Endophytic Actinobacteria are a microbial group that is still poorly investigated. Their association with plants constitutes a unique trait conferring specific biological and chemical features to endophytic Actinobacteria. This contribution discusses aspects of endophytic actinobacterial biology and chemistry comprehensively, including the biosynthesis and total synthesis of secondary metabolites produced in culture. It also presents perspectives for the future of microbial bioactive natural products discovery, with emphasis on the secondary metabolism of endophytic Actinobacteria.


Assuntos
Actinobacteria/química , Produtos Biológicos , Endófitos/química , Plantas/microbiologia , Metabolismo Secundário
14.
Nucleic Acids Res ; 47(9): 4624-4637, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-30916321

RESUMO

The rational discovery of new specialized metabolites by genome mining represents a very promising strategy in the quest for new bioactive molecules. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a major class of natural product that derive from genetically encoded precursor peptides. However, RiPP gene clusters are particularly refractory to reliable bioinformatic predictions due to the absence of a common biosynthetic feature across all pathways. Here, we describe RiPPER, a new tool for the family-independent identification of RiPP precursor peptides and apply this methodology to search for novel thioamidated RiPPs in Actinobacteria. Until now, thioamidation was believed to be a rare post-translational modification, which is catalyzed by a pair of proteins (YcaO and TfuA) in Archaea. In Actinobacteria, the thioviridamide-like molecules are a family of cytotoxic RiPPs that feature multiple thioamides, which are proposed to be introduced by YcaO-TfuA proteins. Using RiPPER, we show that previously undescribed RiPP gene clusters encoding YcaO and TfuA proteins are widespread in Actinobacteria and encode a highly diverse landscape of precursor peptides that are predicted to make thioamidated RiPPs. To illustrate this strategy, we describe the first rational discovery of a new structural class of thioamidated natural products, the thiovarsolins from Streptomyces varsoviensis.


Assuntos
Produtos Biológicos/metabolismo , Biossíntese Peptídica/genética , Peptídeos Cíclicos/genética , Peptídeos/genética , Actinobacteria/química , Actinobacteria/genética , DNA Polimerase Dirigida por DNA/genética , Genoma/genética , Peptídeos/química , Peptídeos/isolamento & purificação , Processamento de Proteína Pós-Traducional/genética , Ribossomos/genética , Streptomyces/genética , Streptomyces/metabolismo , Tioamidas
15.
J Gen Appl Microbiol ; 65(4): 197-203, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30814437

RESUMO

Spirotetronate compounds are polyketide secondary metabolites with diverse biological functions, such as antibacterial, antitumor and antiviral activities. Three pure spirotetronate compounds (2EPS-A, -B, -C) isolated from Actinomadura strain 2EPS showed inhibitory activity against dengue virus serotype 2 (DENV-2). 2EPS-A, -B and -C demonstrated the LC50 values of 11.6, 27.5 and 12.0 µg/ml, respectively, in a test of cytotoxicity to Vero cells. The least cytotoxic, 2EPS-B, was further analyzed for its impact on viral propagation in a cell-based replication assay. At a concentration of 6.25 µg/ml, it could reduce the DENV-2 infection in Vero cells by about 94% when cells infected with DENV-2 were exposed to 2EPS-B, whereas direct treatment of DENV-2 with 2EPS-B at the same concentration prior to subsequent infection to Vero cell yielded no inhibition. 2EPS-A, -B an -C showed strong DENV-2 NS2B-NS3 protease inhibition in an in vitro assay, with IC50 values of 1.94 ± 0.18, 1.47 ± 0.15 and 2.51 ± 0.21 µg/ml, respectively. Therefore, the spirotetronate compounds appear to prevent viral replication and viral assembly by inhibition of the viral protease.


Assuntos
Antivirais/farmacologia , Vírus da Dengue/efeitos dos fármacos , Policetídeos/farmacologia , Actinobacteria/química , Animais , Vírus da Dengue/enzimologia , Vírus da Dengue/fisiologia , Concentração Inibidora 50 , Policetídeos/química , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Sorogrupo , Células Vero , Replicação Viral/efeitos dos fármacos
16.
Int Microbiol ; 22(4): 403-409, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30847714

RESUMO

A biofilm is a community of microorganisms attached to a surface and embedded in a matrix of extracellular polymeric substances. Biofilms confer resistance towards conventional antibiotic treatments; thus, there is an urgent need for newer and more effective antimicrobial agents that can act against these biofilms. Due to this situation, various studies have been done to investigate the anti-biofilm effects of natural products including bioactive compounds extracted from microorganisms such as Actinobacteria. This review provides an insight into the anti-biofilm potential of Actinobacteria against various pathogenic bacteria, which hopefully provides useful information, guidance, and improvements for future antimicrobial studies. Nevertheless, further research on the anti-biofilm mechanisms and compound modifications to produce more potent anti-biofilm effects are required.


Assuntos
Actinobacteria/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Produtos Biológicos/farmacologia , Actinobacteria/metabolismo , Antibacterianos/química , Antibacterianos/metabolismo , Bactérias/efeitos dos fármacos , Produtos Biológicos/química , Produtos Biológicos/metabolismo
17.
BMC Microbiol ; 19(1): 49, 2019 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-30795744

RESUMO

BACKGROUND: Actinobacteria are famous for the production of unique secondary metabolites that help in controlling the continuously emerging drug resistance all over the globe. This study aimed at the investigation of an extreme environment the Cholistan desert, located in southern Punjab, Pakistan, for actinobacterial diversity and their activity against methicillin resistant Staphylococcus aureus (MRSA). The Cholistan desert is a sub-tropical and arid ecosystem with harsh environment, limited rainfall and low humidity. The 20 soil and sand samples were collected from different locations in the desert and the actinobacterial strains were selectively isolated. The isolated strains were identified using a polyphasic taxonomic approach including morphological, biochemical, physiological characterization, scanning electron microscopy (SEM) and by 16S rRNA gene sequencing. RESULTS: A total of 110 desert actinobacterial strains were recovered, which were found to be belonging to 3 different families of the order Actinomycetales, including the family Streptomycetaceae, family Pseudonocardiaceae and the family Micrococcaceae. The most frequently isolated genus was Streptomyces along with the genera Pseudonocardia and Arthrobacter. The isolated strains exhibited promising antimicrobial activity against methicillin resistant Staphylococcus aureus (MRSA) with zone of inhibition in the range of 9-32 mm in antimicrobial screening assays. The chemical profiling by thin layer chromatography, HPLC-UV/Vis and LC-MS analysis depicted the presence of different structural classes of antibiotics. CONCLUSION: The study revealed that Cholistan desert harbors immense actinobacterial diversity and most of the strains produce structurally diverse bioactive secondary metabolites, which are a promising source of novel antimicrobial drug candidates.


Assuntos
Actinobacteria/química , Actinobacteria/classificação , Antibacterianos/farmacologia , Actinobacteria/fisiologia , Antibacterianos/isolamento & purificação , DNA Bacteriano/genética , Clima Desértico , Ecossistema , Variação Genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Paquistão , Filogenia , Análise de Sequência de DNA , Microbiologia do Solo , Esporos Bacterianos/classificação
18.
Org Lett ; 21(4): 900-903, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30714736

RESUMO

This study reported the isolation and characterization of 11 rifamycin congeners including six new ones (1-6) from the agar fermentation extract of Amycolatopsis mediterranei S699. Compounds 1 and 2 are rifamycin glycosides named as rifamycinosides A and B, respectively. Their polyketide skeleton represents a novel cleavage pattern of the rifamycin ansa chain. Compounds 6 and 8 showed potential T3SS inhibitory activity, and 6 induced G2/M phase arrest and caused DNA damage in HCT116 cells.


Assuntos
Actinobacteria/química , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Rifamicinas/farmacologia , Sistemas de Secreção Tipo III/antagonistas & inibidores , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antifúngicos/química , Antifúngicos/isolamento & purificação , Candida albicans/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Células HCT116 , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium smegmatis/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Rifamicinas/química , Rifamicinas/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Sistemas de Secreção Tipo III/metabolismo
19.
Mar Drugs ; 17(2)2019 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-30717397

RESUMO

A cytotoxic alkaloidal meroterpenoid, saccharoquinoline (1), has been isolated from the fermentation broth of the marine-derived bacterium Saccharomonospora sp. CNQ-490. The planar structure of 1 was elucidated by 1D, 2D NMR, and MS spectroscopic data analyzes, while the relative configuration of 1 was defined through the interpretation of NOE spectroscopic data. Saccharoquinoline (1) is composed of a drimane-type sesquiterpene unit in combination with an apparent 6,7,8-trihydroxyquinoline-2-carboxylic acid. This combination of biosynthetic pathways was observed for the first time in natural microbial products. Saccharoquinoline (1) was found to have cytotoxicity against the HCT-116 cancer cell line by inducing G1 arrest, which leads to cell growth inhibition.


Assuntos
Actinobacteria/metabolismo , Antineoplásicos/farmacologia , Terpenos/química , Terpenos/farmacologia , Actinobacteria/química , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Modelos Moleculares , Estrutura Molecular
20.
Microb Ecol ; 77(4): 839-851, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30761424

RESUMO

The quest for novel natural products has recently focused on the marine environment as a source for novel microorganisms. Although isolation of marine-derived actinomycete strains is now common, understanding their distribution in the oceans and their adaptation to this environment can be helpful in the selection of isolates for further novel secondary metabolite discovery. This study explores the taxonomic diversity of marine-derived actinomycetes from distinct environments in the coastal areas of the Yucatan Peninsula and their adaptation to the marine environment as a first step towards novel natural product discovery. The use of simple ecological principles, for example, phylogenetic relatedness to previously characterized actinomycetes or seawater requirements for growth, to recognize isolates with adaptations to the ocean in an effort to select for marine-derived actinomycete to be used for further chemical studies. Marine microbial environments are an important source of novel bioactive natural products and, together with methods such as genome mining for detection of strains with biotechnological potential, ecological strategies can bring useful insights in the selection and identification of marine-derived actinomycetes for novel natural product discovery.


Assuntos
Actinobacteria/química , Antibacterianos/análise , Produtos Biológicos/análise , Descoberta de Drogas/métodos , Água do Mar/análise , México
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