Search Results (129)

Antimicrobial resistance (AMR) has emerged as a global health crisis, with methicillin-resistant Staphylococcus aureus (MRSA) representing one of the most clinically significant multidrug-resistant pathogens. In this study, three structurally unique anthracycline derivatives—keto-ester (1), 4-deoxy-ε-pyrromycinone (2), and misamycin (3)—were first isolated and characterized from the fermentation broth of the marine-derived Streptomyces tauricus NBUD24. These compounds exhibited notable antibacterial efficacy against MRSA, with minimum inhibitory concentrations (MICs) ranging from 16 to 32 µg/mL. Cytotoxicity assays confirmed their safety profile at therapeutic concentrations. The biofilm formation assay demonstrated that 4-deoxy-ε-pyrromycinone inhibited biofilm formation of MRSA ATCC43300, with an inhibition rate of 64.4%. Investigations of antibacterial mechanisms revealed that these compounds exert antibacterial effects primarily through disruption of bacterial cell wall integrity and destruction of DNA structure. These findings underscore the potential of marine-derived microbial metabolites as promising scaffolds for developing next-generation antimicrobial candidates to combat drug-resistant infections. Full article

Heterologous expression of the G231L variant of VioA into 16 strains of marine-derived Streptomyces, combined with bioactivity tracking, leads to the activation of seven antibiotic streptogramins (1–7) in Streptomyces sp. OUC20-O. Among these, compound 1, named linstreptogramin, is a new compound with an unusual linear streptogramin skeleton. The planar structure and stereochemistry of compound 1 were established based on extensive MS and NMR spectroscopic analyses, together with ECD calculations. In the antibacterial activity evaluation, compounds 1–4 showed significant growth inhibition against the multidrug-resistant Enterococcus faecium CCARM 5203 with MIC values of 0.2–1.6 µg/mL, which are comparable to the positive control vancomycin. Full article

Marine Streptomyces are an important source of naturally occurring active compounds. Out of 23 marine Streptomyces strains, 1 strain of Streptomyces sp. FJ0218 was selected for its high activity in inhibiting α-glucosidase. Two polyketides, phaeochromycins D (2) and E (1), were isolated from the fermentation broth of this strain using bioactivity-guided column chromatography over RP-18, Sephadex LH-20, and silica gel. Their structures were determined using NMR data, HR-EI-MS, and single-crystal X-ray crystallography. Phaeochromycins D (2) and E (1) exhibited inhibitory activity against α-glucosidase, with IC₅₀ values of 10 mM and 25 mM, respectively. Lineweaver–Burk plots revealed that phaeochromycin E (1) acts as an uncompetitive inhibitor, while phaeochromycin D (2) acts as a non-competitive inhibitor. These findings suggest that there is potential for the pharmacological regulation of glucose levels through the use of polyketide phaeochromycins, emphasizing their significant impact on glucose management. Full article

Three new structures named naphpyrone I–K (1–3) that contain a 6/6/6/6 oxaphenalene pyranone skeleton were isolated and purified from a marine-derived Streptomyces sp. HDN155000. Their chemical structures, including configurations, were elucidated by extensive NMR, MS, single-crystal X-ray diffraction, theoretical NMR calculations, DP4+ probability analysis, and ECD analyses. Naphpyrone K (3) showed cytotoxic activities against L-02, K562, NCI-H446/EP, MDA-MB-231, and NCI-H446 cancer cells with IC₅₀ values of 5.13, 3.34, 2.50, 2.61, and 2.20 μM, respectively. These findings highlight the potential for screening and developing therapeutic drugs from aromatic polyketides derived from marine actinobacteria. Full article

An Arctic marine-derived strain, MNP-1, was characterized by a combined methodological approach, incorporating a variety of analytical techniques including morphological features, biochemical characteristics, and 16S ribosomal RNA (rRNA) sequence analysis. The chemical investigation of Streptomyces sp. MNP-1 using the OSMAC (one strain many compounds) strategy yielded the isolation of twenty known compounds (1–20), which were unambiguously identified by various spectroscopic approaches including ¹H and ¹³C NMR and ESI-MS (previously reported data). Bioassay results indicated that compounds 2, 3, 5, 9, 14, 15, and 20 had antimicrobial activity against human pathogenic strains including Staphylococcus aureus, Escherichia coli, and Candida albicans with MIC values ranging from 4 to 32 μg/mL, and compounds 3 and 14 exhibited moderate inhibitory activity on A549, MCF-7, and HepG2 tumor lines showing IC₅₀ values within the range of 19.88 to 35.82 µM. These findings suggest that Streptomyces sp. MNP-1 is one of the prolific manufacturers of bioactive secondary metabolites with therapeutic potential. Full article

Endophytic bacteria are an important source for developing antimicrobial substances. With the aim to find eco-friendly antimicrobial agents from natural sources, Streptomyces sp. R6 was isolated from Azadirachta indica. After that, a new spirotetronate natural product, lobophorin S (compound 2), together with lobophorin H8 (compound 1) and a known macrolide compound divergolide C (compound 3) were isolated from the cultural solution of strain R6. These compounds mark the first isolation of marine-derived microbial natural products known as lobophorins (LOBs) from endophytic bacteria. The structures of these three compounds were identified by extensive NMR and HRMS analyses. The antimicrobial activities of these three compounds against eight fungal and four bacterial phytopathogens were separately evaluated. Compound 1 demonstrated better antibacterial activity against Erwinia carotovora, Pseudomonas syringae pv. tomato, and P. syringae pv. lachrymans with MIC values of 3.91, 7.81, and 15.63 μg/mL, respectively. Additionally, compounds 1–3 all showed antifungal activity against Botrytis cinerea, with the MIC values of 1.95, 7.81, and 15.63 μg/mL, respectively. Notably, the in vivo antifungal effect of 1 against B. cinerea was up to 78.51 ± 3.80% at 1.95 µg/mL, significantly surpassing polyoxin B (70.70 ± 3.81%). These results highlight the potential of lobophorins as promising lead compounds for the development of new, sustainable agents to control plant diseases. Full article

In this study, we report the molecular and enzymatic characterisation of Spg103, a novel bifunctional β-glucanase from the marine bacterium Streptomyces sp. J103. Recombinant Spg103 (rSpg103) functioned optimally at 60 °C and pH 6. Notably, Spg103 exhibited distinct stability properties, with increased activity in the presence of Na+ and EDTA. Spg103 displays both lichenase and cellobiohydrolase activity. Despite possessing a GH5 cellulase domain, FN3 and CBM3 domains characteristic of cellulases and CBHs, biochemical assays showed that rSpg103 exhibited higher activity towards mixed β-1,3-1,4-glucan such as barley β-glucan and lichenan than towards beta-1,4-linkages. The endolytic activity of the enzyme was confirmed by TLC and UPLC-MS analyses, which identified cellotriose as the main hydrolysis product. In addition, Spg103 exhibited an exo-type activity, selectively releasing cellobiose units from cellooligosaccharides, which is characteristic of cellobiohydrolases. These results demonstrate the potential of Spg103 for a variety of biotechnological applications, particularly those requiring tailor-made enzymatic degradation of mixed-linked β-glucans. This study provides a basis for further structural and functional investigations of the bifunctional enzyme and highlights Spg103 as a promising candidate for industrial applications. Full article

Melanoma is an aggressive skin cancer with a high risk of cancer-related deaths, and inducing apoptosis in melanoma cells is a promising therapeutic strategy. This study investigates the anti-tumor potential of a novel lucknolide derivative LA-UC as a therapeutic candidate for melanoma. Lucknolide A (LA), a tricyclic ketal-lactone metabolite isolated from marine-derived Streptomyces sp., was chemically modified by introducing a 10-undecenoyl group to synthesize LA-UC. LA-UC preferentially inhibited the proliferation of melanoma cells, including B16F10, while exerting minimal effects on normal melanocytes or other tumor cell types, indicating the selective action of LA-UC against melanoma cells. LA-UC decreased G2/M checkpoint proteins, including cyclin B1 and Cdc2, while activating caspase-3 and caspase-9, resulting in G2/M cell cycle arrest and inducing apoptotic cell death in B16F10 cells. The addition of a pan-caspase inhibitor confirmed the caspase-dependent mechanism of LA-UC-induced cell death. Additionally, LA-UC elevated mitochondrial ROS levels, leading to mitochondrial membrane disruption, upregulation of pro-apoptotic proteins, and DNA damage in melanoma cells. The ROS scavenger N-acetylcysteine reduced LA-UC-induced mitochondrial ROS accumulation, mitochondrial membrane disruption, DNA damage, and apoptosis. Collectively, these findings suggest that LA-UC induces G2/M cell cycle arrest and caspase-dependent apoptosis in B16F10 cells through excessive mitochondrial ROS generation, membrane impairment, and DNA damage, highlighting its potential as a promising therapeutic candidate for melanoma treatment. Full article

Three new depsipeptides, homiamides A–C (1–3), were isolated from a marine sediment-derived strain of Streptomyces sp., ROA-065. The planar structures of homiamides A–C (1–3) were elucidated using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopic data. The absolute configurations of 1–3 were deduced from the application of the Marfey’s method and GC-MS analysis after formation of the O-trifluoroacetylated (S)-(+)-methyl-2-butyl ester derivatives of amino acids. Compounds 1–3 exhibited weak anti-bacterial activities against both Gram-positive bacteria and Gram-negative bacteria, with compound 1 showing MIC values of 32–64 μg/mL. In antifouling assays, compounds 1 and 2 displayed moderate activity against Micrococcus luteus KCTC 3063, while compound 3 exhibited weak activity against all tested bacteria. Full article

Heterologous expression has emerged as an effective strategy in activating Streptomyces cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster spi derived from marine Streptomyces sp. HDN155000 in the chassis host Streptomyces albus J1074. The structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as theoretical NMR calculations and electronic circular dichroism (ECD) calculations. Interestingly, compound WS009 Z (2) contains a rare thiomethyl group, angumycinone T (4) has a novel oxo-bridge formed between C12a and C4, and angumycinone X (3) showed cytotoxicity toward K562 and NCI-H446/EP cell lines. Full article

One of the major global health threats in the present era is antibiotic resistance. Biosynthesized iron oxide nanoparticles (FeNPs) can combat microbial infections and can be synthesized without harmful chemicals. In the present investigation, 16S rRNA gene sequencing was used to discover Streptomyces sp. SMGL39, an actinomycete isolate utilized to reduce ferrous sulfate heptahydrate (FeSO₄.7H₂O) to biosynthesize FeNPs, which were then characterized using UV–Vis, XRD, FTIR, and TEM analyses. Furthermore, in our current study, the biosynthesized FeNPs were tested for antimicrobial and antibiofilm characteristics against different Gram-negative, Gram-positive, and fungal strains. Additionally, our work examines the biosynthesized FeNPs’ molecular docking and binding affinity to key enzymes, which contributed to bacterial infection cooperation via quorum sensing (QS) processes. A bright yellow to dark brown color shift indicated the production of FeNPs, which have polydispersed forms with particle sizes ranging from 80 to 180 nm and UV absorbance ranging from 220 to 280 nm. Biosynthesized FeNPs from actinobacteria significantly reduced the microbial growth of Fusarium oxysporum and L. monocytogenes, while they showed weak antimicrobial activity against P. aeruginosa and no activity against E. coli, MRSA, or Aspergillus niger. On the other hand, biosynthesized FeNPs showed strong antibiofilm activity against P. aeruginosa while showing mild and weak activity against B. subtilis and E. coli, respectively. The collaboration of biosynthesized FeNPs and key enzymes for bacterial infection exhibits hydrophobic and/or hydrogen bonding, according to this research. These results show that actinobacteria-biosynthesized FeNPs prevent biofilm development in bacteria. Full article

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and drug resistance and no targeted drug available at present. Compound 4, a staurosporine alkaloid derived from Streptomyces sp. NBU3142 in a marine sponge, exhibits potent anti-TNBC activity. This research investigated its impact on MDA-MB-231 cells and their drug-resistant variants. The findings highlighted that compound 4 inhibits breast cancer cell migration, induces apoptosis, arrests the cell cycle, and promotes cellular senescence in both regular and paclitaxel-resistant MDA-MB-231 cells. Additionally, this study identified mitogen-activated protein kinase kinase kinase 11 (MAP3K11) as a target of compound 4, implicating its role in breast tumorigenesis by affecting cell proliferation, migration, and cell cycle progression. Full article

A bioassay-guided chemical investigation of a bacterium, Streptomyces sp. CMB-MRB032, isolated from sheep feces collected near Bathurst, Victoria, Australia, yielded the known polyketide antimycins A4a (1) and A2a (2) as potent inhibitors of Dirofilaria immitis (heartworm) microfilaria (mf) motility (EC₅₀ 0.0013–0.0021 µg/mL), along with the octapeptide surugamide A (3) and the new N-methylated analog surugamide K (4). With biological data suggesting surugamides may also exhibit activity against D. immitis, a GNPS molecular network analysis of a library of microbes sourced from geographically diverse Australian ecosystems identified a further five taxonomically and chemically distinct surugamide producers. Scaled-up cultivation of one such producer, Streptomyces sp. CMB-M0112 isolated from a marine sediment collected at Shorncliff, Qld, Australia, yielded 3 along with the new acyl-surugamides A1–A4 (5–8). Solid-phase peptide synthesis provided additional synthetic analogs, surugamides S1–S3 (9–11), while derivatization of 3 returned the semi-synthetic surugamide S4 (12) and acyl-surugamides AS1–AS3 (13–15). The natural acyl-surugamide A3 (7) and semi-synthetic acyl-surugamide AS3 (15) were shown to selectively inhibit D. immitis mf motility (EC₅₀ 3.3–3.4 µg/mL), however, unlike antimycins 1 and 2, were inactive against the gastrointestinal nematode Haemonchus contortus L1–L3 larvae (EC₅₀ > 25 µg/mL) and were not cytotoxic to mammalian cells (human colorectal carcinoma SW620, IC₅₀ > 30 µg/mL). A structure–activity relationship (SAR) study on the surugamides 3–15 revealed that selective acylation of the Lys³-ε-NH₂ correlates with anthelmintic activity. Full article

The marine Streptomyces harbor numerous biosynthetic gene clusters (BGCs) with exploitable potential. However, many secondary metabolites cannot be produced under laboratory conditions. Co-culture strategies of marine microorganisms have yielded novel natural products with diverse biological activities. In this study, we explored the metabolic profiles of co-cultures involving Streptomyces sp. 2-85 and Cladosporium sp. 3-22—derived from marine sponges. Combining Global Natural Products Social (GNPS) Molecular Networking analysis with natural product database mining, 35 potential antimicrobial metabolites annotated were detected, 19 of which were exclusive to the co-culture, with a significant increase in production. Notably, the Streptomyces-Fungus interaction led to the increased production of borrelidin and the discovery of several analogs via molecular networking. In this study, borrelidin was first applied to combat Saprolegnia parasitica, which caused saprolegniosis in aquaculture. We noted its superior inhibitory effects on mycelial growth with an EC₅₀ of 0.004 mg/mL and on spore germination with an EC₅₀ of 0.005 mg/mL compared to the commercial fungicide, preliminarily identifying threonyl-tRNA synthetase as its target. Further analysis of the associated gene clusters revealed an incomplete synthesis pathway with missing malonyl-CoA units for condensation within this strain, hinting at the presence of potential compensatory pathways. In conclusion, our findings shed light on the metabolic changes of marine Streptomyces and fungi in co-culture, propose the potential of borrelidin in the control of aquatic diseases, and present new prospects for antifungal applications. Full article

Four tunicamycin class compounds, tunicamycin VII (1), tunicamycin VIII (2), corynetoxin U17a (3), and tunicamycin IX (4), were isolated from the culture broth of the marine-derived actinomycete Streptomyces sp. MBTG32. The strain was identified using the 16S rDNA sequencing technique, and the isolated strain was closely related to Streptomyces bacillaris. The structures of the isolated compounds were elucidated based on spectroscopic data and comparisons with previously reported NMR data. Compounds 1–4 showed potent antibacterial activities against Gram-positive bacteria, especially Staphylococcus aureus, with MIC values of 0.13–0.25 µg/mL. Through a recombinant enzyme assay and overexpression analysis, we found that the isolated compounds exerted potent inhibitory effects on S. aureus MurNAc-pentapeptide translocase (MraY), with IC₅₀ values of 0.08–0.21 µg/mL. The present results support that the underlying mechanism of action of tunicamycins isolated from marine-derived Streptomyces sp. is also associated with the inhibition of MraY enzyme activity in S. aureus. Full article