Marine Drugs最新文献

Recently, as a result of growing interest in diatoms as sources of energy (biofuel) and valuable food components for humans and aquaculture organisms, new data on the structures and properties of diatom natural products have been obtained, including both endo- and exometabolites. Information about their biosynthesis, biological activity and roles, and their beneficial and hazardous properties has also emerged. The application of modern methods of molecular biology, metabolomics, and chemical ecology to the study of diatom natural products has improved the understanding of many important natural phenomena associated with diatoms, such as photosynthesis, harmful algal blooms, interactions of diatoms with other organisms of marine biota, and their impact on biogeochemical cycles and climate regulation. In this paper, we discuss various aspects of research on natural compounds from diatoms, covering the last decade, as well as prospects for their further development, which have become apparent in recent years.

Alginate is a natural polysaccharide extracted from brown algae and is commonly used as a biomaterial scaffold in tissue engineering. In this study, we performed phenol functionalization of sodium alginate based on chemical modification methods using 1-ethyl-(3-dimethylaminopropyl)carbodiimide/N-hydroxybutanediimide/2-(N-morpholino) ethanesulfonic acid (EDC/NHS/MES) and tyramine. The presence of phenol groups was confirmed by spectrophotometry and Fourier Transform Infrared. We successfully prepared hydrogels using a horseradish peroxidase/hydrogen peroxide (HRP/H₂O₂) enzymatic system as well as an sodium persulfate (SPS)/ruthenium light-crosslinking system. Optimization identified 1 mM ruthenium and 4 mM SPS as the most effective photo crosslinking conditions. At the same time, 1 mM H₂O₂ and 10 U/mL HRP are considered optimal conditions for the enzyme-linked reaction. Rheological measurements monitored the gelation process, revealing that the viscosity, storage modulus, and loss modulus of the material increased by at least one hundredfold after crosslinking. Thixotropy results demonstrated excellent recovery of the material. Texture analysis indicated that the crosslinked material possessed notable strength and toughness, highlighting its potential applications in tissue engineering after 3D bioprinting.

Astaxanthin, one of the most commercially valuable carotenoids, is renowned for its potent antioxidant and anti-inflammatory properties and is experiencing growing demand across diverse industries. To enhance astaxanthin production in Paracoccus marcusii, compound mutagenesis was performed using ethyl methanesulfonate (EMS), ultraviolet (UV) radiation, and atmospheric room temperature plasma (ARTP) treatment. Subsequently, a high-throughput microbial microdroplet culture (MMC) system was employed to select fast-growing microdroplet, followed by screening for high astaxanthin-producing mutants on dual-inhibitor plates. The mutant M21 was isolated and exhibited a significant increase of 16.86% in astaxanthin content (1.53 mg/g) and a 19.81% increase in astaxanthin production (11.71 mg/L) compared with the wild type (WT) (p < 0.05). Moreover, the enhanced phenotype of M21 was genetically stable. Response surface methodology (RSM)-based optimization of fermentation conditions further increased astaxanthin content and production to 1.72 mg/g and 12.92 mg/L, respectively, corresponding to improvements of 16.44% and 23.02% over the WT, while simultaneously reducing culture time, total nitrogen requirements, and sodium lactate consumption, thereby lowering production costs. This study achieved significant enhancement of astaxanthin production through novel mutant breeding and fermentation optimization, underscoring the effectiveness of this integrated strategy for application in industrial biotechnology.

We recently reported that onnamide A, a marine-derived natural compound isolated from the sponge Theonella sp., inhibits the entry process of SARS-CoV-2 infection. However, its antiviral activity against other viruses remains largely unexplored. Here, we investigated the effects of onnamide A and its structurally related analog, onnamide B, on hepatitis B virus (HBV) infection. Using iNTCP cells, a hepatoblastoma-derived cell line permissive to HBV infection, we found that onnamides A and B exhibited cytotoxicity, with CC₅₀ values of 0.53 ± 0.10 μM and 2.37 ± 0.25 μM, respectively. Following HBV infection, the levels of total HBV RNA were significantly reduced by onnamide A (IC₅₀ = 0.06 ± 0.01 μM) and onnamide B (IC₅₀ = 0.23 ± 0.06 μM). Notably, both compounds markedly decreased the levels of HBV pregenomic RNA. Furthermore, significant inhibition was particularly evident when onnamide treatment was initiated after HBV infection. Consistent with these observations, onnamides did not affect HBV binding, entry, or covalently closed circular DNA formation, but they significantly suppressed HBV RNA transcription. In particular, the transcriptional activities driven by the core and X promoters were markedly inhibited by onnamide treatment. Taken together, our findings demonstrate that onnamides possess potent anti-HBV activity and highlight their potential as candidate compounds targeting HBV RNA transcription.

Marine natural products (MNPs) are a diverse group of bioactive compounds with varied chemical structures, but their biological origins are often misannotated due to complex host-microbe symbiosis. Propagated through public databases, such errors hinder biosynthetic studies and AI-driven drug discovery. Here, we develop a structure-based workflow of origin classification and misannotation correction for marine datasets. Using CMNPD and NPAtlas compounds, we integrate a two-step cleaning strategy that detects label inconsistencies and filters structural outliers with a microbial-pretrained graph neural network. The optimized model achieves a balanced accuracy of 85.56% and identifies 3996 compounds whose predicted microbial origins contradict their Animalia labels. These putative symbiotic metabolites cluster within known high-risk taxa, and interpretability analysis reveal biologically coherent structural patterns. This framework provides a scalable quality-control approach for natural product databases and supports more accurate biosynthetic gene cluster (BGC) tracing, host selection, and AI-driven marine natural product discovery.

For the first time, a comparative analysis has been conducted to elucidate the biosynthesis of three families of natural products-staurosporines/rebeccamycins, cladoniamides, and fascaplysins. Based on the available data, a well-founded hypothesis was formed that these metabolites arise through a shared biosynthetic pathway. A comparative evaluation of biological activity profiles and molecular mechanisms of action of the major representatives of these alkaloid families and their derivatives shows that, despite an apparent similarity between the activity spectra of indolo[2,3-a]pyrrolo[3,4-c]carbazoles and fascaplysins, they operate through different mechanisms. The biological effects of fascaplysin are driven primarily by the induction of metabolic stress rather than by the inhibition of DNA topoisomerase I or of a broad-spectrum protein kinases. The successful optimization of natural indolo[2,3-a]pyrrolo[3,4-c]carbazoles-compounds with initially poorer pharmacokinetic properties than those of fascaplysin-to drug-like candidates underscores the substantial pharmaceutical potential of the fascaplysin scaffold. Several existing fascaplysin derivatives, after the improvement of their pharmacokinetic characteristics, may serve as promising leads for the development of a new class of antibiotics.

C-type lectins (CTLs) are a large family of calcium-dependent carbohydrate-binding proteins that play crucial roles in innate immunity as pattern recognition receptors. Bivalve mollusks possess exceptionally diverse and expanded repertoires of CTLs, yet a systematic review integrating their structural, functional, and regulatory aspects has been lacking. This article provides a comprehensive synthesis of current knowledge on bivalve CTLs, analyzing their biosynthesis, complex tissue-specific expression under both normal and stressed conditions, and their multifaceted roles in immune defense and other physiological processes. Our analysis consolidates data on their diverse domain architectures, phylogenetic relationships, and the variability of key motifs within their carbohydrate-recognition domains. The results demonstrate that bivalve CTLs are not only critical for pathogen recognition, agglutination, and phagocytosis but also involved in processes like nutrition, development, byssus formation and biomineralization. However, a significant finding is that the detailed carbohydrate specificity for most bivalve CTLs remains poorly characterized, often limited to monosaccharide inhibition assays. In conclusion, while the immune role of bivalve CTLs is well-established, this review underscores a critical gap in understanding their fine glycan-binding profiles. Therefore, a shift in the focus of future research towards elucidating their structure and carbohydrate specificity is required for a full understanding of their biological functions and an assessment of their biomedical potential.

Mining bioactive secondary metabolites from microorganisms originating from deep-sea cold seep holds significant potential for discovering novel drug lead compounds. In this study, three known indole derivatives (1-3) were isolated from cold-seep-derived Halomonas meridiana OUCLQ22-B7. Subsequently, two-new indole dimers, meribisindole A (4) and meribisindole B (5), with nine known metabolites (6-14) were obtained via indole precursor feeding strategy. The structure of these compounds was elucidated via a combination of spectroscopic methods and circular dichroism (CD) measurement. Antimicrobial assays revealed that compounds 4, 7 and 8 exhibited potent inhibitory activity against Fusarium oxysporum CICC 41029 with minimal inhibitory concentrations (MICs) of 0.39-12.5 μg/mL, and compound 11 showed significant growth inhibition against Staphylococcus aureus CCARM 3090 with MIC value at 0.098 μg/mL.

This study investigated the antioxidant and antiadipogenic activities of sulfated polysaccharide (SPs) from the red seaweed Gracilaria caudata. First, sulfated polysaccharide-rich extracts (SPREs) from fifteen tropical seaweeds were screened to evaluate both their chemical composition and antioxidant potential. Among all samples, G. caudata exhibited the highest total antioxidant capacity, which justified its selection for detailed characterization. Sequential acetone precipitation produced three SPs (F1.5, F2.0, and F3.0), differing in sulfate content, monosaccharide composition, and molecular weight. In vitro assays revealed that F1.5 had the highest total antioxidant capacity and strong iron-chelating activity, while F2.0 exhibited the most effective hydroxyl radical scavenger. Importantly, F1.5 was the only SP that was non-cytotoxic to non-tumor cell lines. In 3T3-L1 preadipocytes, F1.5 attenuated H₂O₂-induced oxidative stress by reducing ROS and MDA levels and restoring GSH and SOD activity, achieving effects comparable to those of quercetin. Moreover, F1.5 inhibited adipogenic differentiation in a dose-dependent manner, as evidenced by decreased Oil Red O staining and reduced glycerol release. Collectively, these findings indicate that F1.5 exerts both antioxidant and antiadipogenic activities, highlighting G. caudata as a promising natural source of bioactive polysaccharides with potential nutraceutical applications. Nonetheless, further studies are required to elucidate the molecular mechanisms underlying these effects, validate the efficacy in vivo, and assess bioavailability and safety before clinical translation can be considered.

In this study, we characterized the holin-like protein ORF70 from the cyanophage MaMV-DC, offering valuable insights into its role in phage-mediated host cell lysis. ORF70 shares key features with class III holins, such as a hydrophobic transmembrane domain and membrane-associated localization, which are crucial for its bacteriolytic activity. Subcellular localization studies suggested its association with the membrane, supporting its classification as a holin-like protein. Overexpression of ORF70 in E. coli resulted in significant growth inhibition, increased β-galactosidase leakage, and visual confirmation of cell death through live/dead staining. Additionally, ORF70's sensitivity to the energy toxin 2,4-dinitrophenol (DNP) further indicated its holin-like activity by promoting membrane depolarization. Transmission electron microscopy and Gram staining revealed characteristic morphological changes in E. coli cells, including membrane disruption, consistent with damage caused by holins. These results suggest that ORF70 acts as a holin-like protein that disrupts the host membrane, leading to bacterial cell death. Our study provides evidence supporting the holin-like activity of ORF70 from cyanophage MaMV-DC. This research significantly enhances our understanding of phage-host interactions and opens new avenues for developing phage-based therapies, offering promising alternatives to traditional antibiotics amidst the growing challenge of antibiotic resistance.