Search Results (237)

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

The purpose of this study was to investigate the taxonomic and phylogenomic placement of the proposed genus ‘Solwaraspora’ within the context of other marine genera using a dual-omics approach. Initially, we isolated bacteria from marine tunicates, squirts, and sponges, which were morphologically similar to an emerging genus (identified as ‘Micromonospora_E’ by the GTDB-tk2 database using whole genome sequence data) by colony shape, size, and clustering pattern, but only found five strains in our dataset belonging to this distinction. Due to the minimally explored nature of this genus, we sought to identify more bacterial strains with similar morphology to Micromonospora‘Micromonospora_E’ by whole genome sequencing (WGS). Within our collection, we noted 35 strains that met this criterion and extracted genomic information to perform WGS on these strains. With this information, we studied taxonomic and phylogenomic relationships among these organisms. Using the data gathered from WGS, we were able to identify an additional five strains labeled by the GTDB-tk2 database as Micromonospora‘Micromonospora_E’, as well as construct phylogenomic trees to examine the evolutionary relationships between these strains. ANI values were calculated between strains from our dataset and type strains of Micromonospora and Plantactinospora as well as against an outgroup Streptomyces strain. No type strains are available for ‘Solwaraspora’. Using MALDI-TOF MS, we positively identified ‘Solwaraspora’, which was supported by the phylogenomic tree showing Micromonospora’Micromonospora_E’ (‘Solwaraspora’) in a distinct clade from Plantactinospora and Micromonospora. Additionally, we discovered gene cluster families (GCFs) in alignment with genera, as well as a large representation of biosynthetic gene clusters (BGCs) coming from the ‘Solwaraspora’ strains. These findings suggest significant potential to discover novel chemistry from ‘Solwaraspora’, adding to the importance of investigating this new genus of bacteria. 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

This study explores the potential anti-H1N1 Influenza A activity of bioactive compounds extracted from Streptomyces ardesiacus, a marine-derived microorganism known for producing diverse secondary metabolites. Four major compounds—1-acetyl-β-carboline, 1H-indole-3-carbaldehyde, anthranilic acid, and indole-3-carboxylic acid—were isolated and characterized through NMR. Among these, the identified structure of 1-acetyl-β-carboline showed the highest IC₅₀ effect, with a dose of 9.71 μg/mL in anti-influenza assays. Using network pharmacology and molecular docking analyses, the interactions of these compounds with key proteins involved in H1N1 pathogenesis were examined. Protein–protein interaction (PPI) networks and Gene Ontology enrichment analysis revealed CDC25B, PARP1, and PTGS2 as key targets, associating these compounds with pathways related to catalytic activity, inflammation, and cell cycle regulation. The molecular docking results demonstrated that 1-acetyl-β-carboline exhibited binding affinities comparable to Tamiflu, the positive control drug, with LibDock scores of 81.89, 77.49, and 89.21 for CDC25B, PARP1, and PTGS2, respectively, compared to Tamiflu’s scores of 84.34, 86.13, and 91.29. These findings highlight the potential of the active compound 1-acetyl-β-carboline from S. ardesiacus as a novel anti-influenza agent, offering insights into their molecular mechanisms of action. The results support further in vitro and in vivo studies to validate the observed inhibitory mechanisms and therapeutic applications against H1N1 Influenza A. Full article

The development of extensive antibiotic resistance has created an urgent demand to identify novel sources of antimicrobial agents. Interest in actinomycetes has become prevalent around the world because of their ability to generate several beneficial bioactive metabolites. In the present study, 32 marine soil samples were collected from Tyre City Beach, Lebanon, in different seasons. A total of 10 actinomycetes species were identified and characterized depending on their microscopic features. All isolates were tested for their potential to exert antimicrobial activities against varied microorganisms using cross-streak and agar well diffusion methods. All isolates displayed significant antimicrobial activities against the tested indicator microorganisms. Similarly, all 10 isolates of marine actinomycetes exhibited antifungal activity in cross-streak tests against Candida albicans, Aspergillus niger, and Aspergillus flavus. Moreover, the optimum conditions used to enhance the production of antimicrobial secondary metabolites against Bacillus cereus were tested for the three isolates Kocuria rosea, Micrococcus luteus, and Streptomyces longisporoflavus. Our results indicate that actinomycetes isolated from Tyre City Beach, Lebanon, represent a promising source of antimicrobial bioactive substances. Full article

Angiogenesis, primarily driven by the vascular endothelial growth factor (VEGF) and its receptor, the VEGFR, plays a key role in various pathological processes such as cancer progression. Here, we investigated the anti-angiogenic effects of Lucknolide A (LA), a marine Streptomyces-derived compound, and evaluated its potential as a VEGFR2 inhibitor. LA selectively inhibited the proliferation of human endothelial cells EA.hy926 and HUVEC while exhibiting minimal effects on normal fibroblasts and various tumor cells. LA induced S-phase cell cycle arrest and apoptosis in EA.hy926 cells, increasing apoptotic markers p53, Bax, and p21 and decreasing the anti-apoptotic protein Bcl-2, with these effects being further enhanced under VEGF stimulation. Additionally, LA suppressed VEGFR2 phosphorylation and its downstream signaling pathways, including Akt/mTOR/p70S6K, MEK/ERK, Src, FAK, and p38 MAPK, which are crucial for endothelial survival and angiogenesis. Molecular docking studies revealed that LA binds to both inactive (DFG-out, PDB: 4ASD) and active (DFG-in, PDB: 3B8R) VEGFR2 conformations, with a significantly stronger affinity for the active state (−107.96 kcal/mol) than the inactive state (−33.56 kcal/mol), suggesting its potential as a VEGFR2 kinase inhibitor. Functionally, LA significantly inhibited VEGF-induced endothelial migration, tube formation, and microvessel sprouting in both in vitro and ex vivo rat aortic ring assays. Additionally, LA reduced tumor-associated tube formation induced by human breast tumor cells (MDA-MB-231), indicating its potential to suppress VEGF-dependent tumor angiogenesis. These findings suggest that LA is a promising selective anti-angiogenic agent with potential therapeutic applications in angiogenesis-related diseases such as cancer. Full article

Talaromyces marneffei (TM) is an opportunistic pathogenic fungus that mainly infects immunocompromised patients. Currently, the global prevalence of talaromycosis caused by TM is increasing, leading to an increased demand for anti-TM drugs. In our previous study, a novel 28-membered macrolide compound, antifungalmycin B (ANB), was isolated from Streptomyces hiroshimensis GXIMD 06359, exhibiting significant antifungal properties. However, its in vivo mechanisms and direct antifungal effects warrant further investigation. In this study, we employed a mouse model in conjunction with transcriptomic and proteomic approaches to explore the antifungal activity of ANB against T. marneffei. In an in vivo mouse model infected with T. marneffei infection, ANB significantly reduced fungal burdens in the liver, spleen, lungs, and kidneys. Additionally, it markedly decreased the levels of reactive oxygen species (ROS) and cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Proteomic and transcriptomic studies, complemented by parallel reaction monitoring (PRM) analysis, revealed that ANB effectively disrupted acid biosynthesis and cellular energy metabolism, thereby impairing mitochondrial functions in T. marneffei. These effects were exerted through multiple pathways. These findings highlight the potential of ANB as a versatile inhibitor of polyene macrolide-resistant fungi, offering a promising therapeutic avenue for the treatment of talaromycosis. 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

The screening of novel antiviral agents from marine microorganisms is an important strategy for new drug development. Our previous study found that polyether K-41A and its analog K-41Am, derived from a marine Streptomyces strain, exhibit anti-HIV activity by suppressing the activities of HIV-1 reverse transcriptase (RT) and its integrase (IN). Among the K-41A derivatives, two disaccharide-bearing polyethers—K-41B and K-41Bm—were found to have potent anti-HIV-1_IIIB activity in vitro. This study aimed to clarify whether K-41B and K-41Bm have inhibitory effects on different HIV-1 strains or whether these two derivatives have mechanisms of action different from that of their precursor, K-41A. An anti-HIV-1 assay indicated that K-41B and K-41Bm have potent anti-HIV-1_BaL activity, with low 50% inhibitory concentrations (IC₅₀s) (0.076 and 0.208 μM, respectively) and high selective indexes (SIs) (58.829 and 31.938, respectively) in the peripheral blood mononuclear cell (PBMC)-HIV-1_BaL system. The time-of-addition (TOA) assay indicated that K-41B and K-41Bm may exert antiviral effects by activating multiple stages of HIV-1 replication. A cell protection assay indicated that the pretreatment of cells with K-41B or K-41Bm has almost no inhibitory effect on HIV-1 infection. A virus inactivation assay indicated that pretreatment of the virus with K-41B or K-41Bm inhibits HIV-1 infection by 60%. A cell–cell fusion assay showed that K-41B and K-41Bm blocked the cell fusion mediated by viral envelope proteins. The HIV-1 key enzyme experiment also indicated that both compounds have certain inhibitory effects on HIV-1 IN. Furthermore, molecular docking showed that K-41B and K-41Bm interact with several viral and host proteins, including HIV-1 IN, an envelope protein (gp120), a transmembrane protein (gp41), and cell surface receptors (CD4, CCR5, and CXCR4). Overall, in addition to having a similar anti-HIV-1 mechanism of inhibiting HIV-1 IN like the precursor polyether K-41A, the disaccharide-bearing polyether derivatives K-41B and K-41Bm may also inhibit viral entry. This suggests that they display anti-HIV-1 mechanisms that are different from those of their precursor polyethers. 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