Marine bacteria thrive in oceanic environments and produce extracellular polysaccharides (EPSs) for cell adhesion and survival under extreme marine living conditions. Due to variations in marine extreme environments, distinct bacterial species occupy specific ecological niches. EPSs, defined by specific chemical components, intricately connect with bacterial habitats and species. In this research, we focused on characterizing marine bacterial EPSs obtained from unique habitats and systematically classified various bacterial types using hierarchical cluster analysis (HCA) and principal component analysis (PCA) to analyze the monosaccharide composition of bacterial EPSs under harsh oceanic conditions. This investigation yielded intriguing insights into the diverse EPSs produced by marine bacteria across various environments. Notably, glucose, mannose, and galactose were found to be highly prevalent in the EPSs of sea-ice bacteria and marine salt lakes; whereas, carboxyl modifications were more pronounced in the EPS derived from deep-sea hydrothermal vents. Notably, the same bacterial species displayed varying EPS profiles contingent upon their specific marine habitats. Furthermore, we explored the potential biomedical applications of marine bacterial EPSs, underscoring the paramount importance of understanding their production mechanisms and potential associations with the surrounding environmental species. In summary, this study highlights the value of investigating marine bacterial EPSs for scientific and medical purposes, offering new insights into their structure, function, and potential applications.
Antimicrobial resistance (AMR) affects multiple fields, including medicine, pharmacy, food safety, and animal husbandry, and poses a major threat to public health and economic development. Staphylococcus aureus has emerged as one of the most critical bacterial pathogens due to its widespread prevalence and significant genetic plasticity. This review outlines currently approved small-molecule drugs for clinical use and their mechanisms in controlling bacterial infections and antimicrobial resistance, highlighting the development of novel agents as an effective strategy to combat AMR. Special emphasis is placed on the antibacterial activity of marine-derived natural products (MNPs) against S. aureus, and a systematic analysis is presented for the first time on the structures, origins, activities, and structure–activity relationships of 1,192 compounds reported in 468 publications from 1977 to 2025. Among these, 36 MNPs exhibited significant activity against both methicillin-sensitive S. aureus and methicillin-resistant S. aureus (MIC ≤ 1 µg/mL). Macrolides and peptides represented the most prevalent structural classes, with compounds displaying potent activity accounting for 24% and 27% of the total active compounds, respectively. Further drug-likeness analysis shows that MNPs have promising therapeutic potential. Among the 160 highly active MNPs, over 80% have suitable lipid-water partition coefficients, and 41% fully meet Lipinski's Rule of Five. Structural analysis reveals tetrahydrofuran, tetrahydropyran, and sugar units as the most common motifs, present in 20, 16, and 14 compounds, respectively. Technologies and strategies to accelerate the development of marine-derived antibacterial drugs are also proposed. This will serve stakeholders across diverse sectors by supporting cross-sectoral coordination to address AMR.
Plant diseases caused by Lasiodiplodia theobromae have expanded in both geographic range and host diversity, posing an increasing threat to agriculture and forestry. Owing to the limited understanding of these diseases and the lack of effective control strategies, the development of novel agricultural fungicides is urgently needed. In this study, eight new naphthoquinone derivatives (1–8), designated fusariumquinones A–H, respectively; two new enoic acids (9 and 10), designated fusariumacids A and B, respectively; and one new natural product (11), designated fusariumacid C, were isolated from the marine-derived fungus Fusarium solani XLGM24, obtained from Acanthus ebracteatus. Their structures and absolute configurations were elucidated using 1D and 2D NMR spectroscopy, HR-ESI-MS, the modified Mosher method, and time-dependent density functional theory electronic circular dichroism calculations. Notably, compound 2 exhibited significant antifungal activity against L. theobromae, with an EC50 value of 19.29 μg/mL, surpassing that of the positive control azoxystrobin (28.98 μg/mL). Mechanistic studies revealed that compound 2 disrupted the permeability and integrity of the cell membrane of L. theobromae, resulting in substantial morphological damage. Physiological assays demonstrated that compound 2 increased malondialdehyde levels, reduced soluble protein content, inhibited the activities of antioxidant enzymes, exacerbated oxidative stress, and disrupted the physiological metabolism of L. theobromae mycelia. In addition, compound 2 enhanced the innate defense responses of mango fruits, thereby increasing their resistance to L. theobromae. These findings identify compound 2 as a promising lead candidate for the development of novel fungicides.
Marine phycotoxins produced by microalgae have traditionally been regarded as water pollutants or hazardous substances. Most studies have focused on their toxicity, with limited exploration of their therapeutic potential. In this study, we demonstrated that domoic acid (DA) exerts antiviral roles against largemouth bass ranavirus (LMBV). Mechanistic analyses revealed that DA disrupts the extracellular structure of LMBV and inhibits intracellular viral assembly. This may be attributed to the ATP depletion caused by the suppression of mitochondrial oxidative phosphorylation. In vivo, DA treatment reduced fish mortality by 12.5% and significantly alleviated pathological lesions in splenic and telencephalic tissues, thereby further confirming its protective effect. Additionally, transcriptomic analysis of liver tissue showed that DA enhanced digestive enzyme activity and activated the complement immune response in LMBV-infected fish. This study uncovers previously unappreciated antiviral activity of marine phycotoxin–DA and elucidates its underlying mechanisms preliminary, laying a foundation for developing marine phycotoxins as antiviral lead compounds.
Uncontrolled bleeding and bacterial infections are major impediments to wound healing. Developing a wound dressing for the skin that possesses both antimicrobial properties and effective hemostatic capabilities is crucial. In this study, a marine polysaccharide-based multifunctional composite sponge was fabricated via chemical cross-linking approach and freeze-drying process. We structurally blended chitosan (CS) with hematite nanotubes (HNT) possessing hemostatic activity. HNT not only effectively promotes blood coagulation by activating coagulation factors but also significantly enhances the structural stability and mechanical properties of the chitosan matrix as a nano-reinforcing agent. Inspired by marine mussel adhesion, polydopamine (PDA) was employed to convert silver ions (Ag+) into silver nanoparticles (PDA@Ag). They were uniformly embedded and stabilized in CS sponges to enhance sustained antimicrobial effects and mitigate cytotoxicity. Compared with gauze, the CS/HNT/PDA@Ag sponge demonstrated excellent hemostatic performance. In rat tail injury experiments, the time to hemostasis was reduced from 89.3 s to 18 s, and blood loss was reduced from 898 to 260 mg. In rat liver injury experiments, the time to hemostasis was reduced from 121 s to 28.7 s, and blood loss was reduced from 1037 to 159 mg. The addition of Ag NPs and the subsequent release of ions significantly reduced bacterial survival rates (> 95%). In a rat full-thickness skin defect infection model, the healing rate of CS/HNT/PDA@Ag sponge reached 99.8% at 14 days of implantation, which effectively promoted collagen deposition, neovascularization and wound healing. By combining the natural biocompatibility of marine-derived CS with the synergistic effects of HNT and mussel-inspired PDA@Ag, the composite sponges offer a highly effective solution for hemostasis and infected wound healing.
Bacterial infections remain a major global health challenge. Marine-derived micro-organisms represent a promising source for the development of anti-infective agents. Structural modification and diversification based on natural products serve as important and effective strategies for the discovery of lead compounds. In this study, we identified four alkanoyl imidazole alkaloids, bulbimidazoles A–D (1–4), from a marine-derived Nocardiopsis strain, with compound 4 being newly reported. During structural characterization, we observed anomalous behavior in the 13C nuclear magnetic resonance (NMR) spectra of these compounds in the form of absent signals corresponding to the three carbons of the imidazole ring and the carbonyl of the acyl side chain. A similar phenomenon was noted in various other compounds containing the imidazole moiety. This observation can be ascribed to the aromaticity and internal double-bond resonance of the imidazole ring. Salt formation of the imidazole derivatives was found to effectively restore the carbon signals, which facilitates structural identification. In addition, N-alkylation of the imidazole ring was shown to normalize NMR signals by locking the double-bond arrangement. A subset of the alkyl-modified derivatives of bulbimidazole B (2) displayed antibacterial activity with varying levels of potency. Notably, derivatives functionalized with n-pentyl, phenethyl, or 2-thienylethyl groups exhibited potent activity against both Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). Mechanistic studies focused on the 2-thienylethyl-modified analog (A38) revealed that its antibacterial function is mediated through disruption of the bacterial cell membrane.
Colorectal cancer is among the most leading cancers in China, characterized by activating mutations in PIK3CA or aberrant AKT signaling in approximately 30%–40% of cases. Marine natural products, especially those derived from marine fungi, offer a valuable source of novel phosphatidylinositol 3-kinase (PI3K) inhibitors. In this study, two novel phenylspirodrimane-type meroterpenoids, chloropenoids A and B (1 and 2), along with ten known analogues (3–12), were isolated from the marine-derived fungus Stachybotrys chlorohalonatus. The absolute configurations of 1 and 2 were established by time-dependent density functional theory electronic circular dichroism (TDDFT-ECD) calculations. Structural optimization via esterification at the C-2′ position of 3 generated a series of derivatives (3a–3i), among which derivative 3a displayed potent antiproliferative activity against CT-26 colorectal cancer cells. Mechanistic studies revealed that 3a disrupted mitochondrial membrane potential, induced apoptosis (total apoptosis rate: approximately 32% at 12.50 μM), and induced G1-phase cell cycle arrest. Molecular docking and Western blot assays demonstrated that 3a effectively inhibited PI3K phosphorylation, consequently attenuating the PI3K/AKT/mTOR signaling cascade. In vivo evaluation using a BALB/c mouse xenograft model revealed that intraperitoneal administration of 3a (50 mg/kg/day for 10 days) significantly suppressed tumor growth (Tumor Growth Inhibition = 85.2%) compared with the control group, exhibiting superior efficacy and reduced systemic toxicity compared to the standard chemotherapy drug, 5-fluorouracil. These findings identify compound 3a as a promising candidate for further development as a PI3K inhibitor for colorectal cancer therapy and provide critical mechanistic insights into phenylspirodrimane-based antitumor agents.
Chitosan–astaxanthin nanoparticles (CS–ASTNPs) exhibited an anti-colitis activity, but their poor mobility restricts anti-inflammatory efficacy. Chlamydomonas reinhardtii (C. reinhardtii) was employed to load CS–ASTNPs to construct astaxanthin-loaded microalgal motors (CS–AST@CR). The particle size of CS–AST@CR was 4.2 ± 0.21 μm and its swimming speed was 89.3 ± 4.4 µm/s, which was slower than native C. reinhardtii (117.2 ± 2.7 µm/s), though their movement trajectories remained comparable. Compared to CS–ASTNPs, CS–AST@CR notably alleviated chronic colitis symptoms. It enhanced colon barrier function by promoting ZO-1, occludin, and MUC2 expression. Furthermore, CS–AST@CR markedly reduced TNF-α, IL-1β, and NLRP3 inflammasome production while increasing IL-10 levels. The oxidative response was effectively suppressed via activating the Nrf2/HO-1 pathway. Additionally, CS–AST@CR significantly increased Lactobacillus and Enterorhabdus abundance; whereas, CS–ASTNPs elevated Akkermansia and Bifidobacteriaceae richness. Collectively, CS–AST@CR integrated the advantages of microalgal motility and nanoparticle functionality, showing great potential for development as functional foods or therapeutic agents for colitis treatment.
Vitiligo is an autoimmune disorder marked by melanocyte destruction and epidermal depigmentation, primarily driven by inflammatory and oxidative stress within the affected skin lesions. Consequently, there is an urgent need for therapeutic strategies focused on protecting melanocytes and replenishing melanin for effective vitiligo management. In this study, a novel microneedle-based therapeutic platform (C/D/E@MN) was fabricated that was composed of cuttlefish ink nanoparticles (CINPs) for melanin supplementation, dipotassium glycyrrhizinate (DPG) for inflammation regulation, and skin-derived exosomes (EXO) to promote melanocyte proliferation. In addition, microneedles with varying dissolution profiles (swellable, slow-dissolving, and fast-dissolving) were designed and evaluated their performance to optimize therapeutic efficacy. In vitro results demonstrated that fast-dissolving microneedles (FDMN) significantly reduced cellular reactive oxygen species (ROS) and the secretion of vitiligo-related inflammatory cytokines and chemokines, such as IL-8, CXCL-16, and HMGB-1. Upon a vitiligo mice model, C/D/E@FDMN treatment group generated a significant increase in skin melanin content and a 15.5% reduction of whitening degree. The microneedles protected melanocytes and promoted lesion repigmentation through synergistic antioxidant, anti-inflammatory and cyto-proliferative mechanisms, offering a promising strategy for improved vitiligo therapy.
Improving the stability and intestinal absorption of antioxidants is a prerequisite for exerting their functional activities. Herein, astaxanthin (AXT)-loaded Lactobacillus rhamnosus GG-derived extracellular vesicles (EVs) (AXT@EVs) were prepared using ultracentrifugation combined with four loading strategies, including ultrasonication, co-incubation, freeze–thaw cycles, and extrusion. Among these methods, AXT@EVs prepared by ultrasonication exhibited the highest encapsulation efficiency. When the mass ratio of AXT to EVs was 1:10, the encapsulation efficiency reached approximately 72.93% and the retention rate remained 98.09% after storage at −80 °C for 90 days. EVs could resist structural damage under harsh environmental conditions, thereby significantly enhancing the stability of AXT under heating and UV exposure and delaying its degradation during simulated digestion. Additionally, the nanoscale structure and good biocompatibility of EVs facilitated the cellular uptake of lipophilic substances by RAW264.7 macrophages. In vivo experiments indicated that Nile Red@EVs showed good intestinal retention and were efficiently absorbed by intestinal epithelial cells. In vitro experiments demonstrated that AXT@EVs significantly reduced reactive oxygen species production, mitochondrial depolarization, and pro-inflammatory cytokines. These findings suggest that EVs not only improve the stability of AXT but also exhibit potent antioxidant and anti-inflammatory effects, providing a strategy for intervening in oxidative stress-related inflammatory responses.
Notopterygium incisum, a traditional medicinal herb widely used for treating rheumatic pain and inflammatory disorders, is an important source of structurally diverse and pharmacologically active coumarins. Using an HTS2-guided screening strategy, we identified 13 previously undescribed coumarins, notoprenylates A–K (compounds 1–11), including two pairs of enantiomers. The structures of these compounds were elucidated through integrated spectroscopic analyses, including HRESIMS, NMR, and chemical calculations, complemented by Mo2(AcO)4-induced circular dichroism experiments. Among these new compounds, notoprenylate F (compound 6) showed mostly inhibition of pro-inflammatory factor NO with a IC50 of 7.01 μmol/L. Transcriptome data from THP-1 cells treated with new compounds collected using the HTS2 platform revealed that compound 6 significantly regulates the PPAR signaling pathway, thereby exerting anti-inflammatory effects. Molecular docking and SPR assays suggested that ompound 6 binds to PPARγ, with a Kd value of 5.3 μmol/L. Furthermore, our results showed that compound 6 acts as a PPARγ agonist, and exerts anti-inflammatory effects by inhibiting PPARγ-mediated MAPK, NF-κB, and NLRP3 inhibition. Molecular docking simulations further confirmed that the hydroxyl group and tricyclic epoxide on the side chain form stable interactions with GLN283 and TYR473. This indicates that the isoprenyl side chain of compound 6 is critical for fitting into the pocket of the PPARγ ligand-binding domain (LBD). Overall, this study not only enriches the chemical diversity of coumarins from N. incisum but also identifies notoprenylate F as a promising PPARγ-targeted anti-inflammatory candidate, providing new insights into the pharmacological potential of traditional medicinal plants.
Vibrio anguillarum is a virulent pathogen responsible for severe diseases in mariculture. Its accurate on-site detection remains a challenge due to limitations in established methods, such as insufficient specificity, prolonged assay, and the requirement of non-movable instruments. We developed a visual platform for the rapid, specific, and sensitive detection of V. anguillarum. It integrates loop-mediated isothermal amplification (LAMP) with DNA-functionalized gold nanoparticles (DNA‒AuNPs); we termed it “nanoprobe-enhanced LAMP.” These DNA‒AuNP probes enabled the colorimetric discrimination of empA expression levels within 20 min, while reducing the limit of detection to 1 fg/μL level (equivalent to 89 CFU/mL). More importantly, this technique demonstrated exceptional specificity in distinguishing V. anguillarum from other Vibrio spp. and foodborne bacteria via selective DNA recognition, outperforming conventional qPCR and fluorescence-based LAMP assays. We also exhibited the applicability of this method by detecting V. anguillarum in various tissues of infected turbots (Scophthalmus maximus), including liver, spleen, kidney, and skin; these results were consistent with the pathological findings. Given its simplicity, portability, and robustness—requiring only a constant temperature source—this approach is ideally suited for field-deployable diagnostics in resource-limited aquaculture settings.
Latency-reversing agents (LRAs) are molecular entities designed to reactivate latent HIV proviruses for subsequent elimination by the immune system or antiviral therapies. Interestingly, in our systematic exploration of fungal pigment diversity, the marine-derived strain Microsphaeropsis arundinis P1B was identified as a prolific azaphilone producer through phenotype-guided screening, suggesting that such fungal compounds may serve as novel LRAs with enhanced efficacy. Further investigation of its solid-fermented rice medium yielded 18 unprecedented sclerotiorin-type azaphilones (microsphazaphilones H–Y, 1–18). Extensive spectroscopic analysis, modified Mosher’s method, TDDFT-ECD calculation, and X-ray diffraction were used to determine their structures including absolute configurations. These compounds exhibit remarkable structural novelty, manifested by features such as unprecedented di- to tetra-carbon truncations in side chains, diverse oxidative modifications (e.g., epoxidation, hydroxylation), or unique stereochemical configurations in the pyranoquinone core. Biological screening identified microsphazaphilone W (16) as a potent HIV LRA. Mechanistic studies confirmed 16 reactivated latent HIV through NF-κB pathway activation, positioning it as a promising candidate for “shock and kill” strategies.
Eleven nardosinane-type compounds, including a norsesquiterpenoid featuring a novel carbon skeleton designated as paralemnanoid A (1), and ten additional norsesquiterpenoids identified as paralemnanoids B − K (2 − 11), were isolated from the South China Sea soft coral Paralemnalia sp.. Comprehensive structural elucidation of compounds 1 − 11 was achieved through an integrated analytical approach, combining including NMR spectroscopy, HRESIMS, single-crystal X-ray diffraction analysis, DP4 + probability assessments, ECD calculations, and literature comparisons. Furthermore, we proposed that the novel poly-isoprenoid scaffold paralemnanoid A (1) originates from paralemnanoid B (2) through sequential oxidative modifications followed by non-enzymatic skeletal rearrangements. The hepatoprotective effects of compounds 1 − 11 were assessed through bioassays, revealing that paralemnanoids A (1) and E (5) exhibited moderate hepatoprotective activity at a concentration of 20 μmol/L in the zebrafish model. This study expands the chemical diversity of marine-derived nardosinane-type terpenoids and provides new insights into their potential therapeutic applications.
Fucose-rich carbohydrates, such as 2'-fucosyllactose and fucoidan, are recognized as anti-infective components that protect the host from pathogens. In this study, the response of the common enteric pathogen Campylobacter jejuni to a specific fucose-containing trisaccharide (GuFGa, β-D-Glcp-(1 → 4)-[β-D-Galp-(1 → 3)]-α-ʟ-Fucp) fermented with human fecal microbiota was investigated using metabolomic and transcriptomic analyses. The protective effect of GuFGa-derived microbial metabolites against C. jejuni was assessed in vitro using a cell-based model. No directly inhibitory effect of GuFGa was observed with the growth of C. jejuni during single-strain cultivation. However, the supernatant of GuFGa fermented with human fecal microbiota (F-GuFGa) reduced the relative abundance of C. jejuni by tenfold within the microbial community. Transcriptome data showed that 128 differentially expressed genes of C. jejuni induced by F-GuFGa treatment were mainly enriched in oxidative phosphorylation and bacterial secretion systems (type IV). Fecal fermentation of GuFGa altered 452 differentially abundant metabolites, which were mainly enriched in phenylalanine and tryptophan metabolism. Correlation analysis indicated that the expression of type IV secretion system genes was significantly negatively correlated with the abundance of phenylacetic acid (PAA) and D-3-phenyllactic acid (D-PLA) (P < 0.05). Adhesion of C. jejuni to Caco-2 cells was reduced by treatment with F-GuFGa, PAA and D-PLA, with the highest inhibition rate observed for F-GuFGa (44.4%), followed by D-PLA (33.3%). This study provides a new perspective for developing GuFGa and similarly fucose-rich oligosaccharides as innovative dietary interventions to inhibit bacterial infections and improve gut health.
Microbial infections and the emergence of antibiotic resistance have become major global health concerns. The continuous search for structurally unique and pharmacologically active compounds derived from natural sources is crucial for the development of new antimicrobial agents. Marine-derived fungi represent a prolific source of chemically diverse natural products with great potential for the discovery of novel antibiotics. In this study, four new naphtho-pyrone dimers, curvupyrones A–D (1–4), six new xanthone dimer derivatives, curvupyrones E–J (5–10), and three known analogs (11–13) were isolated from the mangrove endophytic fungus Curvularia sp. QQYZ-4 under bioactivity-directed guidance and heteronuclear single quantum coherence (HSQC)-based DeepSAT. The planar structures of new compounds 1–10 were elucidated using high-resolution electrospray ionization mass spectrometry (HRESIMS) and 1D/2D NMR. Compounds 1–10 possess complex axial chirality and stereochemical configurations, and their absolute configurations were determined by comprehensive analysis combining energy barrier calculations, nuclear Overhauser effect spectroscopy (NOESY) analysis, Cotton effects, DP4⁺ analysis, and ECD calculations. Notably, 9–12 exhibit significant antimicrobial activity against Escherichia coli (E. coli), Salmonella typhimurium (S. typhimurium), Methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans (C. albicans), with MICs ranging from 2 to 8 μg/mL. Furthermore, scanning electron microscopy (SEM) revealed that compound 9 disrupts the structural integrity of E. coli and S. typhimurium. This study not only enriches the chemical diversity of naphtho-pyrone dimers and xanthone dimer derivatives but also provides a chemical basis for research and development targeting antimicrobial agents.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease for which treatment options remain limited and therapeutic outcomes are often unsatisfactory. In this study, an anti-inflammatory activity-guided investigation led to the isolation of 12 compounds, including 11 new meroterpenoids (1–11) and the known compound aspermeroterpene B (12). Bioaspertermeroterpene A (1) was identified as the first meroterpenoid featuring a novel 6/6/6/7 tetracyclic ring system. In anti-inflammatory assays, compounds 10–12 significantly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages, with IC50 values of 21.0, 26.7, and 14.1 μmol/L, respectively, outperforming the positive control indomethacin (IC50 = 24.1 μmol/L). These compounds also downregulated the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Further mechanistic investigations revealed that compound 12 exerts its anti-inflammatory effects by modulating the PI3K/IκB-α/MAPK signaling pathway. In a dextran sulfate sodium (DSS)-induced murine colitis model, compound 12 demonstrated remarkable therapeutic efficacy by alleviating disease symptoms, restoring intestinal barrier integrity, and suppressing colonic inflammation by downregulating iNOS and tumor necrosis factor-α (TNF-α). Collectively, this study not only reveals a class of structurally novel meroterpenoids with potent anti-UC activity but also identifies compound 12 as a highly promising lead candidate for the treatment of inflammatory bowel disease.
A systematic chemical investigation of the deep-sea-derived fungus Penicillium limosum ZEN48 resulted in the isolation of four new indole-diketopiperazine alkaloids, limopiperazines A–D (1–4), alongside 16 known analogues (5–20). The structures of the new compounds were determined through comprehensive spectroscopic analysis, quantum chemical calculations, X-ray crystallography, and biogenetic considerations. Limopiperazine C (3) potently inhibited osteoclast differentiation and disrupted actin ring formation. Integrated RNA sequencing, RT-qPCR and molecular docking revealed that limopiperazine C exerts the anti-osteoclastogenic effect by modulating the ferroptosis signaling pathway via targeting heme oxygenase-1 (Hmox-1), positioning it as a promising lead compound for developing anti-osteoporotic agents.
Cell-cultured meat, a new cell-based agricultural technology, aims to provide sustainable and safe meat production. Fat is essential for the flavor, texture, and nutritional value of cell-cultured meat. However, research on immortalized fish adipose-derived stem cells remains limited. Here, a continuous marine fish adipose-derived stem cell line, designated EfADS, was successfully established from the visceral adipose tissues of brown-marbled grouper (Epinephelus fuscoguttatus) and sub-cultured beyond 65 times with robust proliferative capacity in L-15 medium supplemented with 20% fetal bovine serum, 10% muscle tissue extract, 5% adipose tissue extract, and 20 ng/mL basic fibroblast growth factor at 28 ℃. The cell lineage origin of EfADS was confirmed by the sustained expression of CD73 and CD105 marker genes from passages 12 to 65. We also developed an efficient adipogenic differentiation medium for EfADS cells, resulting in a 5.3-fold increase in triglyceride content by day 15 post-induction, along with 6.5-fold and 3.3-fold upregulations in the expression of adipogenic marker genes of PPARγ and LPL, respectively. Furthermore, by cultivating EfADS cells on edible microcarriers and subsequently inducing adipogenesis, cell-cultured fish fats were successfully fabricated. The resulting fats exhibited a nutritionally favorable fatty acid profile consisting of ~ 31% saturated fatty acids, ~ 60% monounsaturated fatty acids, and ~ 9% polyunsaturated fatty acids. In conclusion, this study has for the first time established an immortalized fish adipose-derived stem cell line and optimized its growth and differentiation conditions, providing a useful seed cell line for fat-containing cultured fish meat.