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1.
Chem Asian J ; 15(3): 327-337, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31957936

RESUMO

Microbial secondary metabolites (SMs) have long been viewed as a significant source of novel pharmaceutical and agrochemical molecules. With the increasing availability of genomic data, numerous biosynthetic gene clusters (BGCs) have been discovered. Despite the presence of tens of thousands of BGCs that can theoretically produce extremely diverse SMs, many gene clusters remain in a silent state under axenic culture conditions. Co-culture is a promising research approach as it stimulates the expression of cryptic BGCs to produce novel metabolites and also mimics natural interspecies interactions in a laboratory environment. In recent years, the roles of SMs in microbial communication have caught the attention of researchers and our understanding of microbes and their production of remarkable SMs has improved. SMs may be extensively involved in a variety of communication events among microorganisms. We herein summarize certain representative findings in the field of chemical communication involving SMs in co-culture systems.


Assuntos
Bactérias/química , Metabolismo Secundário , Aspergillus fumigatus/química , Aspergillus fumigatus/metabolismo , Aspergillus fumigatus/virologia , Bactérias/metabolismo , Bactérias/virologia , Montagem e Desmontagem da Cromatina , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Streptomyces/química , Streptomyces/metabolismo , Streptomyces/virologia , Vírus/patogenicidade
2.
J Agric Food Chem ; 68(6): 1588-1595, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31994388

RESUMO

The discovery of new, safe, and effective pesticides is one of the main means for modern crop protection and parasitic disease control. During the search for new insecticidal secondary metabolites from endophytes in Stemona sessilifolia (a traditional Chinese medicine with a long history as an insecticide), 10 new insecticidal endostemonines A-J (1-10) were identified from an endophytic Streptomyces sp. BS-1. Their structures were determined by comprehensive spectroscopic analysis. Endostemonines A-J represent the first reported naturally occurring pyrrole-2-carboxylic ester derivatives, which consisted of different fatty acid chains at the C-2 of pyrrole ring were produced by traditional Chinese medicine endophytic microbes. All new tested compounds exhibited strong lethal activity against Aphis gossypii (LC50 value range of 3.55-32.00 mg/L after 72 h). This research highlighted the discovery of pesticide natural products from insecticidal medicinal plant endophytes for the first time, paving a new pathway for the development of pest control.


Assuntos
Endófitos/química , Compostos Heterocíclicos com 3 Anéis/metabolismo , Inseticidas/metabolismo , Stemonaceae/microbiologia , Streptomyces/química , Streptomyces/metabolismo , Animais , Afídeos/efeitos dos fármacos , Endófitos/metabolismo , Compostos Heterocíclicos com 3 Anéis/química , Compostos Heterocíclicos com 3 Anéis/toxicidade , Inseticidas/química , Inseticidas/toxicidade , Metabolismo Secundário
3.
J Agric Food Chem ; 68(4): 1101-1109, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31904947

RESUMO

ε-Poly-l-lysine (ε-PL) consists of 25-35 lysine residues which are linked by an isopeptide bond formed by dehydration condensation of α-carboxyl and ε-amino groups and has good antibacterial activity and broad-spectrum inhibition range. However, there is no clear conclusion about the structure and antibacterial mechanism of ε-PL in aqueous solution. Herein, a high purity of ε-PL was prepared using Amberlite IRC-50 ion-exchange resin. Membrane filtration and dynamic light scattering were used to study the variations of ε-PL aggregation in aqueous solution with pH value. The conformational changes and antibacterial activities of ε-PL and carbamoylated ε-PL in different water environments were studied with circular dichroism (CD) and inhibition zone. The structural changes during the spray-drying process were determined by Fourier transform infrared spectroscopy. The results indicated that the side chain amino charge played a decisive role in the ε-PL conformation and aggregation. ε-PL exhibited the properties of a ß-sheet during spray drying from acidic liquids to solids. The cation enhanced the antibacterial activity of ε-PL but did not play a key role. Instead, the backbone of ε-PL might determine the mechanism of ε-PL antibacterial.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Polilisina/química , Polilisina/farmacologia , Antibacterianos/metabolismo , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Concentração de Íons de Hidrogênio , Transição de Fase , Polilisina/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Streptomyces/química , Streptomyces/metabolismo
4.
Food Chem ; 308: 125600, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31648091

RESUMO

A novel blue pigment was first isolated from Streptomyces sp. A1013Y. The purified component was identified as 4,8,13-trihydroxy-6,11-dione-trihydrogranaticins A (TDTA). Its physical properties were found to be: Molecular weight 462 Da; Color value, E0.1%1cm580 nm = 80; Solubility, it dissolved in organic solvents. In addition, the color of TDTA changed with pH but was found to be relatively stable between 20 and 100 °C, from pH 3 to pH 11, and under UV-light or darkness. TDTA's functional properties was as follows: TDTA showed excellent free radical scavenging properties, IC50 41.04 µg/mL and 13.75 µg/mL using 2, 20-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-n-(3, 2-ethyl-benzothiazole-6-sulfonic acid) ammonium salt (ABTS) respectively. TDTA might be a promising source of natural pigment and bioactive compound used as additive in food industry.


Assuntos
Streptomyces/química , Benzotiazóis/química , Compostos de Bifenilo/química , Cor , Picratos/química , Pigmentação , Solubilidade , Solventes
5.
Chem Commun (Camb) ; 56(5): 822-825, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31848534

RESUMO

Produced by a newly isolated Streptomycetes strain, meijiemycin is a gigantic linear polyene-polyol that exhibits structural features not seen in other members of the polyene-polyol family. We propose a biosynthetic mechanism and demonstrate that meijiemycin inhibits hyphal growth by inducing the aggregation of ergosterol and restructuring of the fungal plasma membrane.


Assuntos
Antifúngicos/farmacologia , Álcoois Graxos/farmacologia , Polienos/farmacologia , Antifúngicos/isolamento & purificação , Antifúngicos/metabolismo , Candida albicans/efeitos dos fármacos , Descoberta de Drogas , Álcoois Graxos/isolamento & purificação , Álcoois Graxos/metabolismo , Genes Bacterianos , Genômica , Testes de Sensibilidade Microbiana , Família Multigênica , Polienos/isolamento & purificação , Polienos/metabolismo , Policetídeo Sintases/genética , Streptomyces/química
6.
Chem Commun (Camb) ; 55(98): 14840-14843, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31768510

RESUMO

XimA is a unique amide synthetase that belongs to the ANL superfamily of adenylating enzymes, but with a special structural fold. In order to improve the enzyme promiscuity, we engineered XimA by site-directed mutagenesis at a specific position based on our theoretical model of XimA. Thus, we were able to produce diverse benzopyran derivatives with up to 15 different l-form and d-form amino acid substitutions, catalyzed by several XimA variants. Molecular docking and molecular dynamics simulations conducted for various XimA systems provide further structural insights into the substitution effects of the phenylalanine-201 as an active site residue on protein dynamics and enzyme catalysis.


Assuntos
Amida Sintases/metabolismo , Treonina/análogos & derivados , Amida Sintases/genética , Benzopiranos/química , Benzopiranos/metabolismo , Cinética , Mutagênese Sítio-Dirigida , Peptídeo Sintases/metabolismo , Engenharia de Proteínas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Streptomyces/química , Streptomyces/metabolismo , Especificidade por Substrato , Treonina/biossíntese , Treonina/química
7.
J Agric Food Chem ; 67(47): 13119-13126, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31686506

RESUMO

Phospholipids have been widely used in food, medicine, cosmetics, and other fields because of their unique chemical structure and healthcare functions. Phospholipase D (PLD) is a key biocatalyst for the biotransformation of phospholipids. Here, an autodisplay expression system was constructed for rapid screening of mutants, and PLD variants were recombined using DNA shuffling technology and three beneficial mutations were obtained. The results of enzymatic performance and sequence information comparison indicated that C-terminal amino acids exerted a greater impact on the correct folding of PLDs, and N-terminal amino acids are more important for catalytic reaction. The best-performing recombinant enzyme in transphosphatidylation reactions was Recom-34, with a phosphatidylserine content accounting for 80.3% of total phospholipids and a 3.24-fold increased conversion rate compared to the parent enzyme. This study demonstrates great significance for screening ideal biocatalysts, facilitating soluble expression of inclusion body proteins, and identifying key amino acids.


Assuntos
Proteínas de Bactérias/genética , Fosfatidilserinas/biossíntese , Fosfolipase D/genética , Streptomyces/enzimologia , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Embaralhamento de DNA , Evolução Molecular Direcionada , Fosfolipase D/química , Fosfolipase D/metabolismo , Dobramento de Proteína , Streptomyces/química , Streptomyces/genética , Streptomyces/metabolismo
8.
Chem Commun (Camb) ; 55(96): 14502-14505, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31730149

RESUMO

ForI is a PLP-dependent enzyme from the biosynthetic pathway of the C-nucleoside antibiotic formycin. Cycloserine is thought to inhibit PLP-dependent enzymes by irreversibly forming a PMP-isoxazole. We now report that ForI forms novel PMP-diketopiperazine derivatives following incubation with both d and l cycloserine. This unexpected result suggests chemical diversity in the chemistry of cycloserine inhibition.


Assuntos
Proteínas de Bactérias/metabolismo , Dicetopiperazinas/química , Formicinas/biossíntese , Fosfato de Piridoxal/química , Piridoxamina/análogos & derivados , Transaminases/metabolismo , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Biocatálise , Domínio Catalítico , Ciclosserina/química , Dicetopiperazinas/metabolismo , Formicinas/química , Concentração de Íons de Hidrogênio , Piridoxamina/química , Piridoxamina/metabolismo , Streptomyces/química , Streptomyces/metabolismo , Transaminases/antagonistas & inibidores , Transaminases/genética
9.
J Agric Food Chem ; 67(41): 11403-11407, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31509401

RESUMO

Three new phenazine metabolites, strepphenazine A-C (1-3), along with a known compound baraphenazine E 4 were isolated from the culture broth of a Streptomyces strain YIM PH20095. The structures were elucidated based on the spectral data. Compounds 1-4 showed different antifungal activity against Fusarium oxysporum, Plectosphaerella cucumerina, Alternaria panax, and Phoma herbarum, which caused root-rot disease of Panax notoginseng with minimal inhibitory concentrations (MICs) of 16-64 µg/mL; compared with compound 4, compounds 1-3 showed better antifungal activity against some of these pathogenic fungi with MICs of 16-32 µg/mL, while compound 4 showed antifungal activity against F. oxysporum, P. cucumerina, and A. panax with the same MICs of 64 µg/mL. Thus, strain YIM PH20095 provides new sources for the development of biological control agents to prevent the infection of pathogenic fungi of P. notoginseng.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Panax notoginseng/microbiologia , Fenazinas/química , Fenazinas/farmacologia , Streptomyces/química , Alternaria/efeitos dos fármacos , Alternaria/crescimento & desenvolvimento , Antifúngicos/isolamento & purificação , Antifúngicos/metabolismo , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fenazinas/isolamento & purificação , Fenazinas/metabolismo , Doenças das Plantas/microbiologia
10.
Pestic Biochem Physiol ; 160: 58-69, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31519258

RESUMO

Microbial antagonists and their bioactive metabolites provide one of the best alternatives to chemical pesticides to control crop disease for sustainable agriculture and global food security. The rice endophyte Streptomyces hygroscopicus OsiSh-2, with remarkable antagonistic activity towards the rice blast fungus Magnaporthe oryzae, was reported in our previous study. The present study deciphered the possible direct interaction mode of OsiSh-2 against M. oryzae. An in vitro antibiotic assay for OsiSh-2 culture filtrate revealed strong suppression of mycelial growth, conidial germination and appressorial formation of M. oryzae. Meanwhile, severe morphological and internal abnormalities in M. oryzae hyphae were observed under a scanning electron microscope and transmission electron microscope. Foliar treatment of rice seedlings by OsiSh-2 culture filtrate in the greenhouse and in the field showed 23.5% and 28.3% disease reduction, respectively. Correspondingly, OsiSh-2 culture filtrate could induce disorganized chitin deposition in the cell wall and lowered ergosterol content in the cell membrane of M. oryzae. Additionally, cell wall integrity pathway activation, large cell electrolytes release, reactive oxygen species accumulation and tricarboxylic acid cycle-related enzyme activity changes were found in M. oryzae. All these results suggested that the direct antagonistic activity of OsiSh-2 against M. oryzae may be attributed to damaging the integrity of the cell wall and membrane and disrupting mitochondrial function in the pathogen.


Assuntos
Antifúngicos/farmacologia , Endófitos/fisiologia , Magnaporthe/efeitos dos fármacos , Oryza/microbiologia , Controle Biológico de Vetores , Streptomyces/química
11.
Nucleic Acids Res ; 47(19): 10296-10312, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31495891

RESUMO

Oxazinomycin is a C-nucleoside antibiotic that is produced by Streptomyces hygroscopicus and closely resembles uridine. Here, we show that the oxazinomycin triphosphate is a good substrate for bacterial and eukaryotic RNA polymerases (RNAPs) and that a single incorporated oxazinomycin is rapidly extended by the next nucleotide. However, the incorporation of several successive oxazinomycins or a single oxazinomycin in a certain sequence context arrested a fraction of the transcribing RNAP. The addition of Gre RNA cleavage factors eliminated the transcriptional arrest at a single oxazinomycin and shortened the nascent RNAs arrested at the polythymidine sequences suggesting that the transcriptional arrest was caused by backtracking of RNAP along the DNA template. We further demonstrate that the ubiquitous C-nucleoside pseudouridine is also a good substrate for RNA polymerases in a triphosphorylated form but does not inhibit transcription of the polythymidine sequences. Our results collectively suggest that oxazinomycin functions as a Trojan horse substrate and its inhibitory effect is attributable to the oxygen atom in the position corresponding to carbon five of the uracil ring.


Assuntos
RNA Polimerases Dirigidas por DNA/química , RNA/química , Transcrição Genética/efeitos dos fármacos , Uridina/análogos & derivados , RNA Polimerases Dirigidas por DNA/genética , Escherichia coli/genética , Oxigênio/química , Pseudomonas/química , RNA/genética , Clivagem do RNA/efeitos dos fármacos , Streptomyces/química , Especificidade por Substrato , Timidina/química , Timidina/genética , Transcrição Genética/genética , Fatores de Elongação da Transcrição/genética , Uracila/química , Uridina/síntese química , Uridina/química , Uridina/farmacologia
12.
Microbiol Res ; 229: 126312, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31434034

RESUMO

Due to emergence of drug resistant pathogens, nearly all available medicines are becoming ineffective against these life threatening pathogens so there is dire need for the discovery of compounds having unique modes of action. During our previous studies, actinomycetes designated as 196 and RI.24 were isolated, screened for bioactive compounds production and characterized using 16S rRNA gene sequencing. Colony 196 was identified as strain of Streptomyces albolongus (100% sequence similarity) and RI.24 as strain of Streptomyces enissocaesilis (100% sequence similarity). In current study, potential bioactive compounds produced by these strains were characterized. Cold extraction method was applied for taking out of bioactive compounds from actinomycetes. Minimum inhibitory concentration (MIC) determination of compounds from these strains showed activity nearly in the range of commercial antibiotics (strain 196 0.0075 mg/ml, RI.24 0.25 mg/ml and chloramphenicol 0.0075 mg/ml, ampicillin 0.025 mg/ml). Structural elucidation of these compounds was carried out using spectroscopic techniques of LC-MS/MS and 1H NMR. Compounds K-252-C-Aglycone, indolocarbazole alkaloid, decoyinine, cycloheximide were detected from strain 196 whereas daunorubicin, hygromycin B, agecorynin F, indinavir-N-glucuronide and minocycline were identified from strain RI.24.Current study reports these compounds for the first time from strains of Streptomyces albolongus and Streptomyces enissocaesilis. Present investigation also suggests that strains 196 and RI.24 contain polyketide synthase-I (PKS-I) and non-ribosomal peptide synthetase (NRPS) gene clusters which are responsible for the production of bioactive compounds. The results of this study can be used by the scientific world or pharmaceutical industries for the development of new drugs/formulations by applying more advanced techniques.


Assuntos
Antibacterianos/química , Antibacterianos/metabolismo , Microbiologia do Solo , Streptomyces/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Estrutura Molecular , Família Multigênica , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Streptomyces/genética , Streptomyces/isolamento & purificação , Streptomyces/metabolismo
13.
J Appl Microbiol ; 127(6): 1727-1740, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31454455

RESUMO

AIMS: To identify and assess the biological activities of the crude extract of a Streptomyces isolate from a salty wetland, an extreme environment likely to induce secondary metabolism of micro-organisms. METHODS AND RESULTS: The crude extract from the isolate Streptomyces lanatus strain AR2 displayed antibacterial activity against Gram-positive bacteria (MICs ranging from 5 to 50 µg ml-1 ) and antioxidant activity as revealed in DPPH (2,2-diphenyl-1-picrylhydrazyl) assay (IC50 of 0·74 mg ml-1 ), ferric reducing antioxidant power (IC50 of 1·12 mg ml-1 ) and metal-chelating power (IC50 of 1·84 mg ml-1 ) assays. Accordingly, the extract attenuated the H2 O2 -induced oxidative stress in the eukaryotic cell model Saccharomyces cerevisiae, assessed by flow cytometry. The profiling of secondary metabolites by HPLC-PDA-ESI-MS/MS revealed the presence of 17 compounds, some of which reported in Streptomyces for the first time to the best of our knowledge: genistein-7-O-glucuronide, naringenin-7-O-rutinoside and resveratrol. CONCLUSIONS: Streptomyces lanatus AR2 produced unique polyketides and phenolic compounds with noticeable bioactivities, allowing adaptation to the extreme environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Sabkhat Seijoumi salty wetland represents a potential niche for Streptomyces yielding useful natural products for biotechnological, pharmaceutical and medical applications.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Streptomyces/química , Antibacterianos/química , Antioxidantes/química , Testes de Sensibilidade Microbiana , Estresse Oxidativo/efeitos dos fármacos , Fenóis/química , Policetídeos/química , Metabolismo Secundário , Streptomyces/isolamento & purificação , Streptomyces/metabolismo , Áreas Alagadas
14.
J Enzyme Inhib Med Chem ; 34(1): 1226-1232, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31307248

RESUMO

Allosamidins come from the secondary metabolites of Streptomyces species, and they have the pseudotrisaccharide structures. Allosamidins are chitinase inhibitors that can be used to study the physiological effects of chitinases in a variety of organisms. They have the novel antiasthmatic activity and insecticidal/antifungal activities. Herein, the synthesis and activities of allosamidins were summarized and analyzed.


Assuntos
Acetilglucosamina/análogos & derivados , Antiasmáticos/farmacologia , Antifúngicos/farmacologia , Inseticidas/farmacologia , Trissacarídeos/farmacologia , Acetilglucosamina/química , Acetilglucosamina/isolamento & purificação , Acetilglucosamina/farmacologia , Animais , Antiasmáticos/química , Antiasmáticos/isolamento & purificação , Antifúngicos/química , Antifúngicos/isolamento & purificação , Asma/tratamento farmacológico , Fungos/efeitos dos fármacos , Humanos , Inseticidas/química , Inseticidas/isolamento & purificação , Conformação Molecular , Mariposas/efeitos dos fármacos , Streptomyces/química , Trissacarídeos/química , Trissacarídeos/isolamento & purificação
15.
Chin J Nat Med ; 17(6): 475-480, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262460

RESUMO

Three new phenazine-type compounds, named phenazines SA-SC (1-3), together with four new natural products (4-7), were isolated from the fermentation broth of an earwig-associated Streptomyces sp. NA04227. The structures of these compounds were determined by extensive analyses of NMR, high resolution mass spectroscopic data, as well as single-crystal X-ray diffraction measurement. Sequencing and analysis of the genome data allowed us to identify the gene cluster (spz) and propose a biosynthetic pathway for these phenazine-type compounds. Additionally, compounds 1-5 exhibited moderate inhibitory activity against acetylcholinesterase (AChE), and compound 3 showed antimicrobial activities against Micrococcus luteus.


Assuntos
Antibacterianos/química , Insetos/microbiologia , Fenazinas/química , Streptomyces/química , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Estrutura Molecular , Família Multigênica , Fenazinas/metabolismo , Fenazinas/farmacologia , Streptomyces/genética , Streptomyces/metabolismo
16.
Zhongguo Zhong Yao Za Zhi ; 44(10): 2090-2095, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31355566

RESUMO

To isolate and identify secondary metabolites of marine-derived Streptomyces sp.MDW-06,the isolations and purifications of compounds were performed by means of column chromatography over silica gel. And their structures were elucidated through the spectroscopic analysis of MS,NMR and specific rotations. The bioactivities were assayed by paper diffusion and DPPH method. From the fermentation broth of marine-derived Streptomyces sp.MDW-06,five compounds( 1-5) were isolated and identified as streptopentanoic acid( 1),germicidin A( 2),germicidin B( 3),isogermicidin A( 4),isogermicidin B( 5) and oxohygrolidin( 6),respectively. Compound 1 is a new compound. Compound 1 shows DPPH radical scavenging activity with 36. 4% at 100 mg·L~(-1).


Assuntos
Depuradores de Radicais Livres/química , Policetídeos/química , Streptomyces/química , Cromatografia , Fermentação , Depuradores de Radicais Livres/isolamento & purificação , Espectroscopia de Ressonância Magnética , Policetídeos/isolamento & purificação
17.
Mar Drugs ; 17(8)2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31357504

RESUMO

Candida albicans is a type of commensal fungi which causes serious infections in immunocompromised patients and contributes to high mortality. In the present study, we identified that the extract from Streptomyces olivaceus SCSIO T05 inhibited hypha and biofilm formation of C. albicans. Seven compounds were isolated and evaluated for their effects on the biological functions and virulence of C. albicans. Two leading compounds, compound 1 (sorbicillin) and compound 2 (3-methyl-N-(2'-phenethyl)-butyrylamide) were identified as exhibiting strong activity against C. albicans morphological transition, adhesion activity, cytotoxicity, and adhesion to human cells, in a dose-dependent manner. Notably, compound 2 inhibited C. albicans infection in mouse oral mucosal models. Transcriptomic analysis and real-time PCR results revealed that compound 2 most likely inhibited the biological functions of C. albicans cells by regulating the expression levels of HWP1, TEC1, ALS1, IFD6, and CSH1, which are associated with filament formation and cell adhesion. Our results suggest that the candidate compounds present excellent efficacy against C. albicans pathogenicity and that they can be developed as potential options for the clinical treatment of candidiasis.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Morfogênese/efeitos dos fármacos , Streptomyces/química , Virulência/efeitos dos fármacos , Células A549 , Animais , Biofilmes/efeitos dos fármacos , Candida albicans/genética , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proteínas Fúngicas/genética , Humanos , Hifas/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mucosa Bucal/microbiologia , Resorcinóis/farmacologia , Transcriptoma/efeitos dos fármacos
18.
Mar Drugs ; 17(6)2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31195687

RESUMO

Bioassay-guided fractionation of marine-derived fungi revealed that the EtOAc fraction from the fermentation broth of a mutated fungal strain Streptomyces nitrosporeus YBH10-5 had lipid-lowering effects in HepG2 cells. Chromatographic separation of the EtOAc fraction resulted in the isolation of 11 PKS-based derivatives, including a structurally unique meroterpenoid namely nitrosporeunol H (1). The structure of compound 1 was determined by the analysis of spectroscopic data. Further bioassay resulted in farnesylquinone (2) and its analogues to exert in vivo fat-reducing effects in C. elegans worm model. The underlying mode of action of compound 2 in the context of live worms was investigated, uncovering that compound 2 enhanced the mitochondrial ß-oxidation rate and changed the transcriptional level of energy metabolism genes. Additional experiments revealed that compound 2 exerted its effects in C. elegans partially through repressing FAT-5, an isoform of stearoyl-CoA desaturase (SCD) which catalyzes the conversion of saturated fatty acids to monounsaturated fatty acids, thereafter leading to the modification of the fatty acid profile. Thus, compound 2 was suggested to be a promising lead for further optimization to treat obesity.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Quinonas/farmacologia , Animais , Caenorhabditis elegans/química , Caenorhabditis elegans/metabolismo , Lipídeos/química , Lipídeos/genética , Oxirredução/efeitos dos fármacos , Quinonas/química , Streptomyces/química , Transcrição Genética/efeitos dos fármacos
19.
Molecules ; 24(12)2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31208056

RESUMO

The strain Streptomyces osmaniensis CA-244599 isolated from the Comoros islands was submitted to liquid-state fermentation coupled to in situ solid-phase extraction with amberlite XAD-16 resin. Elution of the trapped compounds on the resin beads by ethyl acetate afforded seven metabolites, osmanicin (1), streptazolin (2), streptazone C (3), streptazone B1 (4), streptenol C (5), nocardamine (6) and desmethylenylnocardamine (7). Osmanicin (1) is a newly reported unusual scaffold combining streptazolin (2) and streptazone C (3) through a Diels-Alder type reaction. Experimental evidence excluded the spontaneous formation of 1 from 2 and 3. The isolated compounds were evaluated for their ability to inhibit elastase using normal human diploid fibroblasts. Compound 1 exhibited the most potent activity with an IC50 of 3.7 µM.


Assuntos
Alcaloides/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Elastase Pancreática/antagonistas & inibidores , Policetídeos/farmacologia , Streptomyces/química , Alcaloides/biossíntese , Alcaloides/química , Alcaloides/isolamento & purificação , Vias Biossintéticas , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fermentação , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Policetídeos/química , Policetídeos/isolamento & purificação , Policetídeos/metabolismo , RNA Ribossômico 16S/genética , Streptomyces/classificação , Streptomyces/genética
20.
Molecules ; 24(11)2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167388

RESUMO

The glyoxylate cycle is a sequence of anaplerotic reactions catalyzed by the key enzymes isocitrate lyase (ICL) and malate synthase, and plays an important role in the pathogenesis of microorganisms during infection. An icl-deletion mutant of Candida albicans exhibited reduced virulence in mice compared with the wild type. Five diketopiperazines, which are small and stable cyclic peptides, isolated from the marine-derived Streptomyces puniceus Act1085, were evaluated for their inhibitory effects on C. albicans ICL. The structures of these compounds were elucidated based on spectroscopic data and comparisons with previously reported data. Cyclo(L-Phe-L-Val) was identified as a potent ICL inhibitor, with a half maximal inhibitory concentration of 27 µg/mL. Based on the growth phenotype of the icl-deletion mutants and icl expression analyses, we demonstrated that cyclo(L-Phe-L-Val) inhibits the gene transcription of ICL in C. albicans under C2-carbon-utilizing conditions.


Assuntos
Organismos Aquáticos/química , Candida albicans/efeitos dos fármacos , Candida albicans/enzimologia , Dicetopiperazinas/química , Dicetopiperazinas/farmacologia , Isocitrato Liase/antagonistas & inibidores , Streptomyces/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Especificidade por Substrato
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