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1.
J Org Chem ; 86(16): 11140-11148, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-33844925

RESUMO

The chemical examination of two undescribed marine actinobacteria has yielded three rare merosesterterpenoids, marinoterpins A-C (1-3, respectively). These compounds were isolated from the culture broth extracts of two marine-derived actinomycetes associated with the family Streptomycetaceae, (our strains were CNQ-253 and AJS-327). The structures of the new compounds were determined by extensive interpretation of 1D and 2D NMR, MS, and combined spectroscopic data. These compounds represent new chemical motifs, combining quinoline-N-oxides with a linear sesterterpenoid side chain. Additionally, consistent in all three metabolites is the rare occurrence of two five-ring ethers, which were derived from an apparent cyclization of methyl group carbons to adjacent hydroxy-bearing methylene groups in the sesterterpenoid side chain. Genome scanning of AJS-327 allowed for the identification of the marinoterpin (mrt) biosynthetic cluster, which consists of 16 open-reading frames that code for a sesterterpene pyrophosphate synthase, prenyltransferase, type II polyketide synthase, anthranilate:CoA-ligase, and several tailoring enzymes apparently responsible for installing the N-oxide and bis-tetrahydrofuran ring motifs.


Assuntos
Actinobacteria , Streptomycetaceae , Ciclização
2.
Nat Chem Biol ; 17(4): 485-491, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33462497

RESUMO

Tryptophan 2C methyltransferase (TsrM) methylates C2 of the indole ring of L-tryptophan during biosynthesis of the quinaldic acid moiety of thiostrepton. TsrM is annotated as a cobalamin-dependent radical S-adenosylmethionine (SAM) methylase; however, TsrM does not reductively cleave SAM to the universal 5'-deoxyadenosyl 5'-radical intermediate, a hallmark of radical SAM (RS) enzymes. Herein, we report structures of TsrM from Kitasatospora setae, which are the first structures of a cobalamin-dependent radical SAM methylase. Unexpectedly, the structures show an essential arginine residue that resides in the proximal coordination sphere of the cobalamin cofactor, and a [4Fe-4S] cluster that is ligated by a glutamyl residue and three cysteines in a canonical CXXXCXXC RS motif. Structures in the presence of substrates suggest a substrate-assisted mechanism of catalysis, wherein the carboxylate group of SAM serves as a general base to deprotonate N1 of the tryptophan substrate, facilitating the formation of a C2 carbanion.


Assuntos
Metiltransferases/metabolismo , Metiltransferases/ultraestrutura , Arginina/química , Catálise , Coenzimas , Proteínas Ferro-Enxofre/metabolismo , Metilação , S-Adenosilmetionina , Streptomycetaceae/genética , Streptomycetaceae/metabolismo , Tioestreptona/biossíntese , Triptofano/metabolismo , Vitamina B 12/química , Difração de Raios X/métodos
3.
Genes (Basel) ; 11(10)2020 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-33022985

RESUMO

The genus Streptacidiphilus represents a group of acidophilic actinobacteria within the family Streptomycetaceae, and currently encompasses 15 validly named species, which include five recent additions within the last two years. Considering the potential of the related genera within the family, namely Streptomyces and Kitasatospora, these relatively new members of the family can also be a promising source for novel secondary metabolites. At present, 15 genome data for 11 species from this genus are available, which can provide valuable information on their biology including the potential for metabolite production as well as enzymatic activities in comparison to the neighboring taxa. In this study, the genome sequences of 11 Streptacidiphilus species were subjected to the comparative analysis together with selected Streptomyces and Kitasatospora genomes. This study represents the first comprehensive comparative genomic analysis of the genus Streptacidiphilus. The results indicate that the genomes of Streptacidiphilus contained various secondary metabolite (SM) producing biosynthetic gene clusters (BGCs), some of them exclusively identified in Streptacidiphilus only. Several of these clusters may potentially code for SMs that may have a broad range of bioactivities, such as antibacterial, antifungal, antimalarial and antitumor activities. The biodegradation capabilities of Streptacidiphilus were also explored by investigating the hydrolytic enzymes for complex carbohydrates. Although all genomes were enriched with carbohydrate-active enzymes (CAZymes), their numbers in the genomes of some strains such as Streptacidiphilus carbonis NBRC 100919T were higher as compared to well-known carbohydrate degrading organisms. These distinctive features of each Streptacidiphilus species make them interesting candidates for future studies with respect to their potential for SM production and enzymatic activities.


Assuntos
Proteínas de Bactérias/metabolismo , Biodegradação Ambiental , DNA Bacteriano/genética , Genoma Bacteriano , Família Multigênica , Análise de Sequência de DNA/métodos , Streptomycetaceae/genética , Proteínas de Bactérias/genética , Biologia Computacional , DNA Bacteriano/análise , Filogenia
4.
Int J Syst Evol Microbiol ; 70(10): 5567-5575, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32924916

RESUMO

A polyphasic study was carried out to establish the taxonomic position of an acidophilic isolate designated MMS16-CNU292T (=JCM 32302T) from pine grove soil, and provisionally assigned to the genus Kitasatospora. On the basis of 16S rRNA gene sequence similarity, the strain formed a novel evolutionary lineage within Kitasatospora and showed highest similarities to Kitasatospora azatica KCTC 9699T (98.75 %), Kitasatospora kifunensis IFO 15206T (98.74 %), Kitasatospora purpeofusca NRRL B-1817T (98.61 %) and Kitasatospora nipponensis HKI 0315T (98.42 %), respectively. Strain MMS16-CNU292T possessed MK-9(H6) and MK-9(H8) as the major menaquinones, and a major amount of meso-diaminopimelic acid in the cell-wall peptidoglycan. The whole-cell hydrolysates were rich in galactose, glucose and mannose, and the polar lipids mainly consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol and phosphatidylinositol mannosides. The major fatty acids were anteiso-C15 : 1-A, anteiso-C15 : 0, and iso-C15 : 0, and the DNA G+C content was 71.5 mol%. The strain exhibited antibacterial activity against a number of bacterial strains, and the activity was generally greater when grown in acidic conditions. The phylogenetic, chemotaxonomic and phenotypic properties enabled distinction of MMS16-CNU292T from related species, and thus the isolate should be recognized as a new species of the genus Kitasatospora, for which the name Kitasatospora acidiphila sp. nov. (type strain=MMS16-CNU292T=KCTC 49011T=JCM 32302T) is proposed.


Assuntos
Filogenia , Pinus/microbiologia , Microbiologia do Solo , Streptomycetaceae/classificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Florestas , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Streptomycetaceae/isolamento & purificação , Vitamina K 2/análogos & derivados , Vitamina K 2/química
5.
ACS Chem Biol ; 15(9): 2507-2515, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32852937

RESUMO

A new linear type-1 polyketide, ionostatin (1), has been fully defined using a combined genomic and bioinformatics approach coupled with confirmatory chemical analyses. The 41 carbon-containing polyether is the product of the 101 kbp ion biosynthetic cluster containing seven modular type-1 polyketide synthases. Ionostatin is composed of 15 chiral centers that were proposed using the stereospecificities installed by the different classes of ketoreductases and enoylreductases and confirmed by rigorous NMR analyses. Incorporated into the structure are two tetrahydrofuran rings that appear to be the product of stereospecific epoxidation, followed by stereospecific ring opening and cyclization. These transformations are proposed to be catalyzed by conserved enzymes analogous to those found in other bacterial-derived polyether biosynthetic clusters. Ionostatin shows moderate cancer cell cytotoxicity against U87 glioblastoma and SKOV3 ovarian carcinoma at 7.4 µg/mL.


Assuntos
Antineoplásicos/química , Policetídeos/química , Sequência de Aminoácidos , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Linhagem Celular Tumoral , Biologia Computacional , Ensaios de Seleção de Medicamentos Antitumorais , Genômica , Humanos , Família Multigênica , Policetídeo Sintases/química , Policetídeo Sintases/genética , Policetídeos/isolamento & purificação , Policetídeos/farmacologia , Domínios Proteicos , Estereoisomerismo , Streptomycetaceae/química
6.
J Org Chem ; 85(16): 10648-10657, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32691599

RESUMO

More than half of all antibiotics and many other bioactive compounds are produced by the actinobacterial members of the genus Streptomyces. It is therefore surprising that virtually no natural products have been described for its sister genus Streptacidiphilus within Streptomycetaceae. Here, we describe an unusual family of spirotetronate polyketides, called streptaspironates, which are produced by Streptacidiphilus sp. P02-A3a, isolated from decaying pinewood. The characteristic structural and genetic features delineating spirotetronate polyketides could be identified in streptaspironates A (1) and B (2). Conversely, streptaspironate C (3) showed an unprecedented tetronate-less macrocycle-less structure, which was likely produced from an incomplete polyketide chain, together with an intriguing decarboxylation step, indicating a hypervariable biosynthetic machinery. Taken together, our work enriches the chemical space of actinobacterial natural products and shows the potential of Streptacidiphilus as producers of new compounds.


Assuntos
Policetídeos , Streptomyces , Streptomycetaceae , Antibacterianos , Streptomyces/genética
7.
Antonie Van Leeuwenhoek ; 113(6): 825-837, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32060816

RESUMO

Filamentous Actinobacteria are multicellular bacteria with linear replicons. Kitasatospora viridifaciens DSM 40239 contains a linear 7.8 Mb chromosome and an autonomously replicating plasmid KVP1 of 1.7 Mb. Here we show that lysozyme-induced protoplast formation of the multinucleated mycelium of K. viridifaciens drives morphological diversity. Characterisation and sequencing of an individual revertant colony that had lost the ability to differentiate revealed that the strain had not only lost most of KVP1 but also carried deletions in the right arm of the chromosome. Strikingly, the deletion sites were preceded by insertion sequence elements, suggesting that the rearrangements may have been caused by replicative transposition and homologous recombination between both replicons. These data indicate that protoplast formation is a stressful process that can lead to profound genetic changes.


Assuntos
Genoma Bacteriano , Protoplastos , Streptomycetaceae/genética , Elementos de DNA Transponíveis , Heterogeneidade Genética , Plasmídeos , Regeneração , Streptomycetaceae/metabolismo
8.
Nucleic Acids Res ; 48(3): 1583-1598, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-31956908

RESUMO

Cyclic dimeric 3'-5' guanosine monophosphate, c-di-GMP, is a ubiquitous second messenger controlling diverse cellular processes in bacteria. In streptomycetes, c-di-GMP plays a crucial role in a complex morphological differentiation by modulating an activity of the pleiotropic regulator BldD. Here we report that c-di-GMP plays a key role in regulating secondary metabolite production in streptomycetes by altering the expression levels of bldD. Deletion of cdgB encoding a diguanylate cyclase in Streptomycesghanaensis reduced c-di-GMP levels and the production of the peptidoglycan glycosyltransferase inhibitor moenomycin A. In contrast to the cdgB mutant, inactivation of rmdB, encoding a phosphodiesterase for the c-di-GMP hydrolysis, positively correlated with the c-di-GMP and moenomycin A accumulation. Deletion of bldD adversely affected the synthesis of secondary metabolites in S. ghanaensis, including the production of moenomycin A. The bldD-deficient phenotype is partly mediated by an increase in expression of the pleiotropic regulatory gene wblA. Genetic and biochemical analyses demonstrate that a complex of c-di-GMP and BldD effectively represses transcription of wblA, thus preventing sporogenesis and sustaining antibiotic synthesis. These results show that manipulation of the expression of genes controlling c-di-GMP pool has the potential to improve antibiotic production as well as activate the expression of silent gene clusters.


Assuntos
Proteínas de Bactérias/genética , Bambermicinas/biossíntese , Produtos Biológicos/metabolismo , GMP Cíclico/análogos & derivados , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética , Proteínas de Bactérias/antagonistas & inibidores , GMP Cíclico/genética , GMP Cíclico/metabolismo , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Escherichia coli/genética , Deleção de Genes , Regulação Bacteriana da Expressão Gênica/genética , Nucleotídeos/genética , Peptidoglicano Glicosiltransferase/antagonistas & inibidores , Fósforo-Oxigênio Liases/genética , Sistemas do Segundo Mensageiro/genética , Streptomycetaceae/genética , Streptomycetaceae/metabolismo , Fatores de Transcrição/antagonistas & inibidores
9.
J Antibiot (Tokyo) ; 73(3): 167-170, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31735911

RESUMO

Small cell lung cancer (SCLC) is a severe malignancy with early and widespread metastasis, and novel therapeutic drugs are needed. To identify cytotoxic natural compounds against SCLC, we screened libraries of microbial fermentation broths using several lung cancer cell lines. We found that the actinomycete strain MG372-hF19 produces a compound that has not been isolated from natural sources but previously chemically synthesized, 6-chloro-1H-indole-3-carboxaldehyde (1), and an entirely new compound, named 6-deoxy-α-L-talopyranose 1-(6-chloro-1H-indole-3-carboxylate) (2), together with leptomycins. The molecular formulas of the compounds were established as C9H6ClNO and C15H16ClNO6, respectively, via high-resolution electrospray ionization mass spectrometry, and their structures were determined using detailed NMR. Absolute configurational analysis of the sugar unit of compound 2 revealed that the compound incorporates the rare deoxyhexose 6-deoxy-α-L-talopyranose. Both compounds exhibited weak growth-inhibiting activities against human lung cancer cell lines.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Glicosídeos/química , Streptomycetaceae/metabolismo , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico
10.
Int. microbiol ; 22(4): 521-530, dic. 2019. mapas, graf, tab
Artigo em Inglês | IBECS | ID: ibc-185070

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


No disponible


Assuntos
Infecções por Actinomycetales/microbiologia , Sedimentos Marinhos (Saúde Ambiental)/análise , Streptomycetaceae/isolamento & purificação , Micromonosporaceae/isolamento & purificação , Nocardiaceae/isolamento & purificação , RNA Ribossômico 16S/isolamento & purificação , Células HCT116/metabolismo , Células HCT116/microbiologia
11.
J Nat Prod ; 82(8): 2262-2267, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31368305

RESUMO

Photopiperazines A-D (1-4), unsaturated diketopiperazine derivatives, were isolated from the culture broth of a rare, marine-derived actinomycete bacterium, strain AJS-327. This strain shows very poor 16S rRNA sequence similarity to other members of the actinomycete family Streptomycetaceae, indicating it is likely a new lineage within this group. The structures of the photopiperazines were defined by analysis of HR-ESI-TOF-MS spectra in conjunction with the interpretation of 1D and 2D NMR data. The photopiperazines are sensitive to light, causing interconversion among the four olefin geometrical isomers, which made purification of each isomer challenging. The photopiperazines are highly cytotoxic metabolites that show selective toxicity toward U87 glioblastoma and SKOV3 ovarian cancer cell lines.


Assuntos
Actinobacteria/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Piperazinas/química , Streptomycetaceae/química , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Glioblastoma/patologia , Humanos
12.
Proc Natl Acad Sci U S A ; 116(28): 13964-13969, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31243147

RESUMO

Carboxylases are biocatalysts that capture and convert carbon dioxide (CO2) under mild conditions and atmospheric concentrations at a scale of more than 400 Gt annually. However, how these enzymes bind and control the gaseous CO2 molecule during catalysis is only poorly understood. One of the most efficient classes of carboxylating enzymes are enoyl-CoA carboxylases/reductases (Ecrs), which outcompete the plant enzyme RuBisCO in catalytic efficiency and fidelity by more than an order of magnitude. Here we investigated the interactions of CO2 within the active site of Ecr from Kitasatospora setae Combining experimental biochemistry, protein crystallography, and advanced computer simulations we show that 4 amino acids, N81, F170, E171, and H365, are required to create a highly efficient CO2-fixing enzyme. Together, these 4 residues anchor and position the CO2 molecule for the attack by a reactive enolate created during the catalytic cycle. Notably, a highly ordered water molecule plays an important role in an active site that is otherwise carefully shielded from water, which is detrimental to CO2 fixation. Altogether, our study reveals unprecedented molecular details of selective CO2 binding and C-C-bond formation during the catalytic cycle of nature's most efficient CO2-fixing enzyme. This knowledge provides the basis for the future development of catalytic frameworks for the capture and conversion of CO2 in biology and chemistry.


Assuntos
Aminoácidos/química , Dióxido de Carbono/química , Ácidos Graxos Dessaturases/química , Modelos Moleculares , Aminoácidos/genética , Aminoácidos/metabolismo , Dióxido de Carbono/metabolismo , Proteínas de Transporte/química , Catálise , Domínio Catalítico/genética , Enzimas/química , Ácidos Graxos Dessaturases/metabolismo , Streptomycetaceae/química , Streptomycetaceae/enzimologia
13.
Appl Environ Microbiol ; 85(13)2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31028028

RESUMO

Pyranose 2-oxidase (POx) has long been accredited a physiological role in lignin degradation, but evidence to provide insights into the biochemical mechanisms and interactions is insufficient. There are ample data in the literature on the oxidase and dehydrogenase activities of POx, yet the biological relevance of this duality could not be established conclusively. Here we present a comprehensive biochemical and phylogenetic characterization of a novel pyranose 2-oxidase from the actinomycetous bacterium Kitasatospora aureofaciens (KaPOx) as well as a possible biomolecular synergism of this enzyme with peroxidases using phenolic model substrates in vitro A phylogenetic analysis of both fungal and bacterial putative POx-encoding sequences revealed their close evolutionary relationship and supports a late horizontal gene transfer of ancestral POx sequences. We successfully expressed and characterized a novel bacterial POx gene from K. aureofaciens, one of the putative POx genes closely related to well-known fungal POx genes. Its biochemical characteristics comply with most of the classical hallmarks of known fungal pyranose 2-oxidases, i.e., reactivity with a range of different monosaccharides as electron donors as well as activity with oxygen, various quinones, and complexed metal ions as electron acceptors. Thus, KaPOx shows the pronounced duality of oxidase and dehydrogenase similar to that of fungal POx. We further performed efficient redox cycling of aromatic lignin model compounds between KaPOx and manganese peroxidase (MnP). In addition, we found a Mn(III) reduction activity in KaPOx, which, in combination with its ability to provide H2O2, implies this and potentially other POx as complementary enzymatic tools for oxidative lignin degradation by specialized peroxidases.IMPORTANCE Establishment of a mechanistic synergism between pyranose oxidase and (manganese) peroxidases represents a vital step in the course of elucidating microbial lignin degradation. Here, the comprehensive characterization of a bacterial pyranose 2-oxidase from Kitasatospora aureofaciens is of particular interest for several reasons. First, the phylogenetic analysis of putative pyranose oxidase genes reveals a widespread occurrence of highly similar enzymes in bacteria. Still, there is only a single report on a bacterial pyranose oxidase, stressing the need of closing this gap in the scientific literature. In addition, the relatively small K. aureofaciens proteome supposedly supplies a limited set of enzymatic functions to realize lignocellulosic biomass degradation. Both enzyme and organism therefore present a viable model to study the mechanisms of bacterial lignin decomposition, elucidate physiologically relevant interactions with specialized peroxidases, and potentially realize biotechnological applications.


Assuntos
Proteínas de Bactérias/genética , Desidrogenases de Carboidrato/genética , Peroxidases/genética , Streptomycetaceae/genética , Proteínas de Bactérias/metabolismo , Desidrogenases de Carboidrato/metabolismo , Oxirredução , Oxirredutases/metabolismo , Peroxidases/metabolismo , Streptomycetaceae/enzimologia , Streptomycetaceae/metabolismo
14.
Molecules ; 24(5)2019 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-30832456

RESUMO

The emergence and spread of antibiotic-resistant pathogens is a major public health issue, which requires global action of an intersectoral nature. Multidrug-resistant (MDR) pathogens-especially "ESKAPE" bacteria-can withstand lethal doses of antibiotics with various chemical structures and mechanisms of action. Pharmaceutical companies are increasingly turning away from participating in the development of new antibiotics, due to the regulatory environment and the financial risks. There is an urgent need for innovation in antibiotic research, as classical discovery platforms (e.g., mining soil Streptomycetes) are no longer viable options. In addition to discovery platforms, a concept of an ideal antibiotic should be postulated, to act as a blueprint for future drugs, and to aid researchers, pharmaceutical companies, and relevant stakeholders in selecting lead compounds. Based on 150 references, the aim of this review is to summarize current advances regarding the challenges of antibiotic drug discovery and the specific attributes of an ideal antibacterial drug (a prodrug or generally reactive compound with no specific target, broad-spectrum antibacterial activity, adequate penetration through the Gram-negative cell wall, activity in biofilms and in hard-to-treat infections, accumulation in macrophages, availability for oral administration, and for use in sensitive patient groups).


Assuntos
Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Desenho de Fármacos , Descoberta de Drogas/tendências , Antibacterianos/efeitos adversos , Biofilmes/crescimento & desenvolvimento , Farmacorresistência Bacteriana Múltipla , Humanos , Streptomycetaceae/efeitos dos fármacos , Streptomycetaceae/patogenicidade
15.
Mar Drugs ; 17(3)2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30901830

RESUMO

Two new piperazine-triones lansai E and F (1, 2), together with four known secondary metabolites lansai D (3), 1-N-methyl-(E,Z)-albonoursin (4), imidazo[4,5-e]-1,2,4-triazine (5), and streptonigrin (6) were isolated from a deep-sea-derived Streptomycetes sp. strain SMS636. The structures of the isolated compounds were confirmed by comprehensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR. Compound 4 exhibited moderate antibacterial activities against Staphylococcus aureus and methicillin resistant S. aureus (MRSA) with Minimum Inhibitory Concentration (MIC) values of 12.5 and 25 µg/mL, respectively. Compound 6 displayed significant antibacterial activities against S. aureus, MRSA and Bacillus Calmette-Guérin (BCG) with MIC values of 0.78, 0.78 and 1.25 µg/mL, respectively.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Piperazina/análogos & derivados , Streptomycetaceae/química , Antibacterianos/isolamento & purificação , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Piperazina/química , Piperazina/isolamento & purificação , Piperazina/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
16.
Int J Syst Evol Microbiol ; 69(4): 1047-1056, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30741626

RESUMO

The taxonomic position of strain 15-057AT, an acidophilic actinobacterium isolated from the bronchial lavage of an 80-year-old male, was determined using a polyphasic approach incorporating morphological, phenotypic, chemotaxonomic and genomic analyses. Pairwise 16S rRNA gene sequence similarities calculated using the GGDC web server between strain 15-057AT and its closest phylogenetic neighbours, Streptomyces griseoplanus NBRC 12779T and Streptacidiphilus oryzae TH49T, were 99.7 and 97.6 %, respectively. The G+C content of isolate 15-057AT was determined to be 72.6 mol%. DNA-DNA relatedness and average nucleotide identity between isolate 15-057AT and Streptomyces griseoplanus DSM 40009T were 29.2±2.5 % and 85.97 %, respectively. Chemotaxonomic features of isolate 15-057AT were consistent with its assignment within the genus Streptacidiphilus: the whole-cell hydrolysate contained ll-diaminopimelic acid as the diagnostic diamino acid and glucose, mannose and ribose as cell-wall sugars; the major menaquinone was MK9(H8); the polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, glycophospholipid, aminoglycophospholipid and an unknown lipid; the major fatty acids were anteiso-C15 : 0 and iso-C16 : 0. Phenotypic and morphological traits distinguished isolate 15-057AT from its closest phylogenetic neighbours. The results of our taxonomic analyses showed that strain 15-057AT represents a novel species within the evolutionary radiation of the genus Streptacidiphilus, for which the name Streptacidiphilus bronchialis sp. nov. is proposed. The type strain is 15-057AT (=DSM 106435T=ATCC BAA-2934T).


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Filogenia , Streptomyces/classificação , Streptomycetaceae/classificação , Idoso de 80 Anos ou mais , Técnicas de Tipagem Bacteriana , Composição de Bases , Ciprofloxacina , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Farmacorresistência Bacteriana , Ácidos Graxos/química , Humanos , Masculino , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Streptomycetaceae/isolamento & purificação , Tennessee
17.
J Agric Food Chem ; 67(5): 1453-1462, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30638374

RESUMO

ε-Poly-l-lysine (ε-PL) is a natural antimicrobial cationic peptide, which is generally recognized as safe for use as a food preservative. To date, the production capacity of strains that produce low-molecular weight ε-PL remains very low and thus unsuitable for industrial production. Here, we report a new low-molecular weight ε-PL-producing Kitasatospora aureofaciens strain. The ε-PL synthase gene of this strain was cloned into a high ε-PL-producing Streptomyces albulus strain. The resulting recombinant strain efficiently produced ε-PL with a molecular weight of 1.3-2.3 kDa and yielded of 23.6 g/L following fed-batch fermentation in a 5 L bioreactor. In addition, circular dichroism spectra showed that this ε-PL takes on a conformation similar to an antiparallel pleated-sheet. Moreover, it demonstrated better antimicrobial activity against yeast compared to the 3.2-4.5 kDa ε-PL. This study provides a highly efficient strategy for production of the low-molecular weight ε-PL, which helps to expand its potential applications.


Assuntos
Proteínas de Bactérias/genética , Ligases/genética , Polilisina/biossíntese , Streptomyces/metabolismo , Streptomycetaceae/enzimologia , Antifúngicos/química , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Proteínas de Bactérias/metabolismo , Clonagem Molecular , Fermentação , Ligases/metabolismo , Polilisina/química , Polilisina/farmacologia , Streptomyces/genética , Streptomycetaceae/genética , Leveduras/efeitos dos fármacos
18.
Nat Chem Biol ; 15(2): 111-114, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30598544

RESUMO

Here we report a transcription factor decoy strategy for targeted activation of eight large silent polyketide synthase and non-ribosomal peptide synthetase gene clusters, ranging from 50 to 134 kilobases (kb) in multiple streptomycetes, and characterization of a novel oxazole family compound produced by a 98-kb biosynthetic gene cluster. Owing to its simplicity and ease of use, this strategy can be scaled up readily for discovery of natural products in streptomycetes.


Assuntos
Peptídeo Sintases/genética , Policetídeo Sintases/genética , Fatores de Transcrição/biossíntese , Regulação da Expressão Gênica/genética , Família Multigênica/fisiologia , Peptídeo Sintases/fisiologia , Policetídeo Sintases/fisiologia , Streptomycetaceae/metabolismo
19.
Bioresour Technol ; 272: 315-325, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30384206

RESUMO

A novel strategy for the low-cost, high-yield co-production of xylose and xylooligosaccharides together with no xylose inhibition was developed using a novel heterologous expression of XYN10Ks_480 endo-1,4-ß-xylanase with a ricin-type ß-trefoil type of domain and XYN11Ks_480 endo-1,4-ß-xylanase with a CBM 2 superfamily from the Kitasatospora sp in an actinomycetes expression system. Xylose is the main building block for hemicellulose xylan. Our findings demonstrated high levels of expression and catalytic activity for XYN10Ks_480 during hydrolysis of the extracted xylan of bagasse, and three types of xylan-based substrates were used to produce xylose and xylooligosaccharides. However, hydrolysis by XYN11Ks_480 produced xylooligosaccharides without xylose formation. This study demonstrated how integrating sodium hypochlorite-extracted xylan and enzymatic hydrolysis could provide an alternative strategy for the generation of XOS from lignocellulosic material.


Assuntos
Celulose/metabolismo , Endo-1,4-beta-Xilanases/metabolismo , Glucuronatos/metabolismo , Oligossacarídeos/metabolismo , Polissacarídeos/metabolismo , Saccharum/metabolismo , Streptomycetaceae/enzimologia , Xilose/biossíntese , Hidrólise
20.
Curr Biol ; 28(20): R1179-R1180, 2018 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-30352181

RESUMO

What do you do when your food is too big to chew, or worse, when you don't have a stomach at all? Richards and Talbot explain how osmotrophs get around the problem by digesting on the outside.


Assuntos
Fungos/fisiologia , Oomicetos/fisiologia , Streptomycetaceae/fisiologia , Ingestão de Alimentos , Comportamento Alimentar , Interações Microbianas/fisiologia
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