Marine-derived Actinomycete Streptomyces Sp Research Articles

Diverse ansamycin derivatives from the marine-derived Streptomyces sp. ZYX-F-97 and their antibacterial activities

Four new ansamycin derivatives, named 1,19-epithio-geldanamycin A (1), 17-demethoxylherbimycin H (2), herbimycin M (3), and seco-geldanamycin B (4), together with eight known ansamycin analogues (5–12) were isolated from the solid fermentation of marine-derived actinomycete Streptomyces sp. ZYX-F-97. The structures of new compounds were elucidated by extensive spectroscopic analysis as well as nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculations. All the compounds were assayed for their antibacterial activity. Among them, compounds 4, 8, and 12 exhibited remarkable inhibition against Listeria monocytogenes with minimum inhibitory concentrations (MIC) values ranging from 8 μg·mL−1 to 64 μg·mL−1, and displayed moderate inhibition against methicillin-resistant Staphylococcus aureus (MRSA) with MIC value of 64 μg·mL−1. Compounds 4, 8, 9, and 12 showed moderate inhibition activities against both Staphylococcus aureus and Bacillus subtilis with MIC values ranging from 32 μg·mL−1 to 128 μg·mL−1.

Cytotoxic and Antifungal Staurosporine Derivatives from Marine-Derived Actinomycete Streptomyces sp. ZS-A121.

A novel staurosporine derivate, streptomholyrine A (1), along with 6 known compounds were identified from the rice-based solid fermentation of marine-derived Streptomyces sp. ZS-A121. The planar structure and absolute configuration of streptomholyrine A were elucidated using a combination of 1D, 2D NMR, HRESIMS data analysis, chemical transformation, ECD and NMR calculations. Screening of all these compounds revealed their cytotoxic activity against HCT-116 cell lines, with IC50 values ranging from 0.012 to 11.67 μM, except for the known 1H-indole-3-hydroxyacetyl, which showed no inhibition activity. Furthermore, streptomholyrine A, along with two known staurosporine derivatives, k252d and staurosporine, exhibited activities against Candida albicans, with MICs of 12.5, 25.0 and 50.0 μg/ml, respectively.

Iseoic acids and bisiseoate: three new naphthohydroquinone/naphthoquinone-class metabolites from a coral-derived Streptomyces.

Two new naphthohydroquinone derivatives designated iseoic acids A (1) and B (2) and a new symmetrical glycerol bisester of naphthoquinonepropanoic acid designated bisiseoate (3) were isolated from the culture extract of a marine-derived actinomycete Streptomyces sp. DC4-5. The structures of 1-3 were determined by analyzing one- and two-dimensional NMR data and MS analytical data. The absolute configurations were determined by NOESY analysis and the phenylglycine methyl ester (PGME) method for 1 and by considering the structural similarity and biosynthesis for 2 and 3. Compound 3 exhibited modest cytotoxicity against P388 murine leukemia cells with an IC50 value of 19 μM.

Antiproliferative Activity and Potential Mechanism of Marine-Sourced Streptoglutarimide H against Lung Cancer Cells.

In 2019, streptoglutarimide H (SGH) was characterized as a new glutarimide from the secondary metabolites produced by a marine-derived actinomycete Streptomyces sp. ZZ741 and shown to have in vitro antiglioma activity. However, the antiproliferative activity and potential mechanism of SGH against lung cancer cells have not yet been characterized. This study demonstrated that SGH significantly inhibited the proliferation of different lung cancer cells. In terms of mechanism of action, SGH downregulated cell cycle- and nucleotide synthesis-related proteins to block cell cycle at G0/G1 phase, reduced the expression levels of glycolytic metabolic enzymes to inhibit glycolysis, and downregulated the important cancer transcription factor c-Myc and the therapeutic target deubiquitinase USP28. Potent anticancer activity and multiple mechanisms indicated SGH to be a novel antitumor compound against lung cancer cells.

Gephyromycin C, a novel small-molecule inhibitor of heat shock protein Hsp90, induces G2/M cell cycle arrest and apoptosis in PC3 cells in vitro

Gephyromycin C (GC), a natural compound isolated from a marine-derived actinomycete Streptomyces sp. SS13I, which exerts anti-proliferative effect on PC3 cells. However, its underlying mechanism of the anti-cancer effect remains unknown. The results of SRB assays showed that GC inhibited the proliferation of PC3 cells with an IC50 value of 1.79 ± 0.28 μM. GC also induced G2/M cell cycle arrest which was accompanied by declining levels of cyclin proteins. Possible mechanisms were investigated and it was found that GC bound to Hsp90 and caused the degradation of Hsp90 client proteins (AKT, CHK1, P53, CDK4, Raf-b, and Raf-1). The fluorescent polarization assay with FITC-labeled geldanamycin (FITC-GA) demonstrated that GC was able to compete with FITC-GA in binding to wild type Hsp90 with an IC50 of 2.15 μM. Results of a docking study also suggested that GC interacted with the N-terminal domain of Hsp90. Our results showed that GC could bind to Hsp90, which resulted in down-regulation of Hsp90 client proteins and G2/M arrest in PC3 cells. Since the antitumor effects of this kind of angucycline via targeting Hsp90 has not been reported before, our results indicate that GC is a novel inhibitor of Hsp90 from marine resources and worthy of further study.

2-Epi-anthracimycin, a new cytotoxic agent from the marine-derived actinomycete Streptomyces sp. OPMA00631.

A new cytotoxic agent designated as 2-epi-anthracimycin (1) was isolated along with anthracimycin and anthracimycin B (2-demethylanthracimycin) from the culture broth of the marine-derived actinomycete Streptomyces sp. OPMA00631. The structure of 1 was elucidated based on spectroscopic analyses (1D and 2D NMR data and ROESY correlations). Compound 1 exhibited cytotoxicity against Jurkat cells with an IC50 value of 50.5 μM in 20 h. The effect of 1 on the cell cycle distribution of Jurkat cells was investigated. Compound 1 (7.80 μM) increased G1 phase cells from 51.1 to 62.0% and conversely, decreased G2 and M phase cells from 30.7 to 19.3 % in 20 h. At a higher concentration, 1 (250 μM) markedly increased subG1 phase cells (1.9% at 0 h to 16.5% at 20 h), while the proportion of G1 phase cells was maintained (62.3%). These results suggest that 1 exhibits cytotoxicity against Jurkat cells by arresting the cell cycle at the G1 phase.

Novel 1,3-Benzodioxole From Marine-Derived Actinomycete in East Vietnam Sea

Analysis of an antimicrobial extract from the culture broth of the marine-derived actinomycete Streptomyces sp. G261 led to the isolation of a new 1,3-benzodioxole derivative (1), together with 10 known compounds 2-11. The actinomycete strain G261 was isolated from sediment, collected at Cu Lao Cham, Quang Nam in Vietnam. The taxonomic identification of the strain G261 was achieved by analysis of 16SrRNA gene sequences. On the basis of morphological and phylogenetic evidence, the actinomycete strain G261 was assigned to the genus Streptomyces. The structures of the isolated compounds were established by their spectral data analysis, including mass spectrometry, 1-dimensional nuclear magnetic resonance (1D-NMR), and 2D-NMR. The structure of 1 was confirmed by comparison of the calculated with experimental13C NMR data. Compound 1 exhibited antimicrobial activity against Enterococcus faecalis and Staphylococcus aureus with minimum inhibitory concentration values of 128 and 256 µg/mL, respectively. Whereas, compound 1 had a weak inhibition when tested against 4 cancer cell lines, KB, LU-1, HepG-2, and MCF-7.

A new compound from the marine-derived Streptomyces sp. SS13M

As part of our efforts toward search for structurally new and bioactive natural products from marine-derived microorganisms, one new compound (1) was characterized from a marine-derived actinomycete Streptomyces sp. SS13M. The structure of new compound was elucidated by the analysis of HRESIMS, 1D, and 2D NMR spectroscopic data, and the absolute configuration was determined by ECD calculations.

2-Alkyl-4-hydroxyquinolines from a Marine-Derived Streptomyces sp. Inhibit Hyphal Growth Induction in Candida albicans.

Four 2-alkyl-4-hydroxyquinoline derivatives (1–4) were isolated from a semisolid rice culture of the marine-derived actinomycete Streptomyces sp. MBTG13. The structures of these compounds were elucidated by a combination of spectroscopic methods, and their data were in good agreement with previous reports. Compounds 1 and 2 exhibited weak to moderate antibacterial activity against pathogenic bacteria. Unexpectedly, we found that compound 1 acted as a potent inhibitor of hyphal growth induction in the dimorphic fungus Candida albicans, with an IC50 value of 11.4 μg/mL. Growth experiments showed that this compound did not inhibit yeast cell growth, but inhibited hyphal growth induction. Semi-quantitative reverse transcription (RT)-PCR analysis of hyphal-inducing signaling pathway components indicated that compound 1 inhibited the expression of mRNAs related to the cAMP-Efg1 pathway. The expression of HWP1 and ALS3 mRNAs (hypha-specific genes positively regulated by Efg1, an important regulator of cell wall dynamics) was significantly inhibited by the addition of compound 1. These results indicate that compound 1 acts on the Efg1-mediated cAMP pathway and regulates hyphal growth in Candida albicans.

A rare diketopiperazine glycoside from marine-sourced Streptomyces sp. ZZ446

Two diketopiperazines were isolated from a culture of the marine-derived actinomycete Streptomyces sp. ZZ446. Their structures were elucidated as maculosin (1) and maculosin-O-α-L-rhamnopyranoside (2) based on their NMR and HRESIMS data, specific rotation, and chemical degradation. Maculosin-O-α-L-rhamnopyranoside (2) is a new diketopiperazine glycoside, a structural class not reported previously from the natural sources. Both compounds showed antimicrobial activity against methicillin-resistant Staphylococcus aureus, Escherichia coli, and Candida albicans with MIC values in a range from 26.0 to 37.0 μg/mL.

Antimicrobial metabolites from a marine-derived Actinomycete Streptomyces sp. G278

Analysis of an antimicrobial extract prepared from culture broth of the marine-derived actinomycete Streptomyces sp. G278 led to the isolation of ten compounds, 1-10. Two compounds, 2,5-Bis(5-tert-butyl-2-benzoxazolyl)thiophene (1), and 3-hydroxyl-2-methylpyridine (2) were isolated from a natural source for the first time. The structures of the isolated compounds were established by their spectral data analysis, including mass spectrometry, 1D-NMR, 2D-NMR, and X-ray crystallographic analysis in case of compound 3. All isolated compounds were evaluated for their antimicrobial activity against a panel of clinically significant microorganisms. Compounds 1 and 3 selectively inhibited Enterococcus faecalis (MIC: 256 μg/mL). Compound 2 was found to have antibacterial and antifungal activity against Escherichia coli (MIC: 64 μg/mL), Salmonella enterica (MIC: 256 μg/mL), Staphylococcus aureus (MIC: 256 μg/mL), Enterococcus faecalis (MIC: 256 μg/mL), and Candida albicans (MIC: 64 μg/mL). Except for compounds 9 and 10, the other known metabolites (4-8) also exhibited antimicrobial activity.

Pteridic acids C-G spirocyclic polyketides from the marine-derived Streptomyces sp. SCSGAA 0027.

Five new pteridic acids C-G (1-5) were isolated from a culture broth of the marine-derived actinomycete Streptomyces sp. SCSGAA 0027. Their complete structures were elucidated on the basis of NMR data, modified Mosher's method and quantum chemical calculations. Furthermore, their cytotoxicity, antiviral and antimicrobial activities were also evaluated.

Neo-actinomycins A and B, natural actinomycins bearing the 5H-oxazolo[4,5-b]phenoxazine chromophore, from the marine-derived Streptomyces sp. IMB094

Neo-actinomycins A and B (1 and 2), two new natural actinomycins featuring an unprecedented tetracyclic 5H-oxazolo[4,5-b]phenoxazine chromophore, were isolated from the marine-derived actinomycete Streptomyces sp. IMB094. Their structures were elucidated by spectroscopic analyses. The presence of this ring system was proposed to originate from a condensation between actinomycin D (3) with α-ketoglutarate and pyruvate, respectively. Compound 1 showed potent cytotoxic activities against human cancer HCT116 and A549 cell lines in the nanomolar range (IC50: 38.7 and 65.8 nM, respectively) and moderate antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) strains.

New Metabolites and Bioactive Actinomycins from Marine-Derived Streptomyces sp. ZZ338.

An extract prepared from the culture of a marine-derived actinomycete Streptomyces sp. ZZ338 was found to have significant antimicrobial and antiproliferative activities. A chemical investigation of this active extract resulted in the isolation of three known bioactive actinomycins (1–3) and two new metabolites (4 and 5). The structures of the isolated compounds were identified as actinomycins D (1), V (2), X0β (3), 2-acetylamino-3-hydroxyl-4-methyl-benzoic acid methyl ester (4), and N-1S-(4-methylaminophenylmethyl)-2-oxo-propyl acetamide (5) based on their nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectroscopy (HRESIMS) data as well as their optical rotation. This class of new compound 5 had never before been found from a natural resource. Three known actinomycins showed activities in inhibiting the proliferation of glioma cells and the growth of methicillin-resistant Staphylococcus aureus, Escherichia coli, and Candida albicans and are responsible for the activity of the crude extract. Actinomycin D (1) was also found to downregulate several glioma metabolic enzymes of glycolysis, glutaminolysis, and lipogenesis, suggesting that targeting multiple tumor metabolic regulators might be a new anti-glioma mechanism of actinomycin D. This is the first report of such a possible mechanism for the class of actinomycins.

Angucycline antibiotics and its derivatives from marine-derived actinomycete Streptomyces sp. A6H

Vineomycin A1 (1) and B2 (2) were isolated from the culture broth of marine actinomycete Streptomyces sp. A6H. Five hydrolysis products were obtained by rational hydrolysis and methanolysis of the fermentation extract. Their structures were characterised as aquayamycin (3), vineomycinone B2 (4), 9-C-D-olivosyltetrangulol (5), 7-O-methylgaltamycinone (6) and vineomycinone B2 methyl ester (7). In addition to these compounds, two ester derivatives, vineolactone A (8) and vineomycinone B2 benzyl ester (9) of compound 4 were generated semisynthetically. Compound 6 is a new analogue of galtamycinone, while compounds 8 and 9 are new members of vineomycins. Cytotoxic activities and antimicrobial activities were determined for all compounds. The results indicate that only compound 1 showed significant activities with IC50 value of 0.34 μM against H1975 and MIC value of 4 μg/mL against Staphylococcus aureus.

Diketopiperazine Derivatives from the Marine-Derived Actinomycete Streptomyces sp. FXJ7.328

Five new diketopiperazine derivatives, (3Z,6E)-1-N-methyl-3-benzylidene-6-(2S-methyl-3-hydroxypropylidene)piperazine-2,5-dione (1), (3Z,6E)-1-N-methyl-3-benzylidene-6-(2R-methyl-3-hydroxypropylidene)piperazine-2,5-dione (2), (3Z,6Z)-3-(4-hydroxybenzylidene)-6-isobutylidenepiperazine-2,5-dione (3), (3Z,6Z)-3-((1H-imidazol-5-yl)-methylene)-6-isobutylidenepiperazine-2,5-dione (4), and (3Z,6S)-3-benzylidene-6-(2S-but-2-yl)piperazine-2,5-dione (5), were isolated from the marine-derived actinomycete Streptomyces sp. FXJ7.328. The structures of 1–5 were determined by spectroscopic analysis, CD exciton chirality, the modified Mosher’s, Marfey’s and the C3 Marfey’s methods. Compound 3 showed modest antivirus activity against influenza A (H1N1) virus with an IC50 value of 41.5 ± 4.5 μM. In addition, compound 6 and 7 displayed potent anti-H1N1 activity with IC50 value of 28.9 ± 2.2 and 6.8 ± 1.5 μM, respectively. Due to the lack of corresponding data in the literature, the 13C NMR data of (3Z,6S)-3-benzylidene-6-isobutylpiperazine-2,5-dione (6) were also reported here for the first time.

Streptobactin, a Tricatechol-Type Siderophore from Marine-Derived Streptomyces sp. YM5-799

A new catechol-type siderophore, streptobactin (1), was isolated from a culture broth of the marine-derived actinomycete Streptomyces sp. YM5-799. The structure of streptobactin was determined by NMR and MS analyses and ESIMS/MS experiments to be a cyclic trimer of benarthin. A dibenarthin (2), a tribenarthin (3), and benarthin (4) were also obtained. The production of 1 was regulated by an iron concentration in the culture. The iron-chelating activity of the compounds was evaluated by the chrome azurol sulfonate assay.