Marine Drugs最新文献

Marine sponges are recognized as reservoirs of diverse microorganisms that produce bioactive natural compounds. In this study, we conducted a metataxonomic analysis of Geodia cydonium specimens collected from four sites in Italy: Secca delle Fumose (Gulf of Naples, Tyrrhenian Sea), Mar Piccolo of Taranto and an Integrated Multi-Trophic Aquaculture (IMTA) system in Mar Grande of Taranto (both located in the Ionian Sea), and Polignano a Mare (Adriatic Sea). Our results revealed a highly diverse microbial community within the sponges, encompassing 24 bacterial phyla. Among these, Chloroflexota was the most abundant phylum, accounting for an average of 30.2% of the total community across all samples. In addition, the majority of the microbiota was composed of Actinomycetota, Proteobacteria, Acidobacteriota, Poribacteriota, Gemmatimonadota, and Dadabacteria. The sponge sample from Polignano a Mare exhibited the richest and most diverse bacterial community. This observation was supported by phylogenetic analysis, which identified seven bacterial genera, Albidovulum, Filomicrobium, Microtrix, Gaiellales, D90 (Gammaproteobacteria class), and Blastopirellula, exclusive to this site. Several of these taxa are known for their potential biotechnological applications, underlining the significance of site-specific microbial diversity in G. cydonium.

Recently, we found that Lystar5 protein from coelomic cells of A. rubens starfish interacts with nicotinic acetylcholine receptors (nAChRs) and integrin α8-like protein. We hypothesized that Lystar5 mediates detachment of coelomic cells from the matrix and their migration. Skin wound healing in humans is based on keratinocytes migration and is regulated by nAChRs and integrins. Here, we revealed that Lystar5 stimulates migration of human skin HaCaT keratinocytes and peripheral blood monocytes. Using ELISA, we found that Lystar5 binds to the membrane fraction of coelomic cells with its loops I and II, which form an active site of Lystar5 and resemble its pro-migratory activity. In keratinocytes and monocytes, Lystar5 and the peptides mimicking its loops I and II bound with α3, α4, and β2 nAChR and α5, αV, and β1 integrin subunits, which form molecular complexes. In keratinocytes, Lystar5 and its mimetics promoted short-term E/N cadherin switch and upregulated expression of α5 and αV integrins, EGFR, and ICAM-1. In keratinocytes and monocytes, Lystar5 and its mimetics upregulated E-selectin secretion. The ability of Lystar5 and its mimetics to stimulate skin keratinocyte migration and immune cell infiltration may be considered promising for the development of new wound-healing agents.

Microalgae represent some of the most promising eukaryotic platforms in biotechnology due to their rapid growth, simple cultivation requirements, reliance on sunlight as a primary energy source, and ability to synthesize high-value bioactive compounds. These characteristics have made microalgae attractive candidates in various fields, including biofuel production, carbon capture, and pharmaceutical development. However, several technical limitations have limited their large-scale use as sustainable biofactories. A paradigm shift is currently occurring thanks to the genetic manipulation of microalgae, driven by CRISPR-Cas technology. Significant progress has been made in the model species Chlamydomonas reinhardtii, particularly in the targeted and efficient insertion of foreign DNA. Despite this progress, key challenges remain, and further optimization of CRISPR-Cas methodologies is needed to fully unleash the genetic potential of this organism. This review provides an overview of the convergence of CRISPR-Cas technologies in microalgae research, highlighting their impact on genetic studies, metabolic engineering, and industrial applications. It summarizes recent advances in microalgal genome editing through CRISPR systems, outlines current technical challenges, and highlights future directions for improving the implementation of this innovative technology in microalgal biotechnology.

Oyster peptides (OPs) have gained increasing attention for their excellent biological activities, especially immunomodulatory effects. In this study, oyster proteins were fermented using Lactobacillus casei to prepare bioactive peptides, and the effects of fermentation parameters (time, temperature, and inoculum amount) on the degree of hydrolysis (DH) were optimized. The optimal fermentation conditions were determined as 30 h, 35 °C, and 5% inoculum amount, resulting in a DH of 28.24%. Structural characterization showed that OPs were mainly composed of low-molecular-weight peptides (<1000 Da) with high hydrophobic amino acid content, and they exhibited good stability during in vitro gastrointestinal digestion. In vitro immunological evaluation using RAW264.7 macrophages demonstrated that OPs significantly enhanced phagocytic activity and nitric oxide (NO) production, and upregulated the mRNA expression levels of pro-inflammatory cytokines including interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. Mechanistically, OPs exerted immunostimulatory effects by specifically activating the extracellular signal-regulated kinase (ERK) pathway within the mitogen-activated protein kinase (MAPK) signaling cascade, without significant alterations in the phosphorylation levels of p38 and c-Jun N-terminal kinase (JNK). These findings highlight the potential of Lactobacillus casei-fermented oyster peptides as natural immunomodulatory ingredients for functional food development.

Astaxanthin, a high-value keto-carotenoid with potent antioxidant and health-promoting properties, has gained global attention as a sustainable nutraceutical and biotechnological product. The green microalgae Haematococcus pluvialis and Chromochloris zofingiensis represent two promising natural producers, yet they differ markedly in physiology, productivity, and industrial scalability. This review provides a focused comparative analysis of these two species, emphasizing their quantitative performance differences. H. pluvialis can accumulate astaxanthin up to ~3-5% of dry biomass but typically reaches biomass densities of only 5-10 g L^-1, whereas C. zofingiensis achieves ultrahigh biomass concentrations of 100-220 g L^-1 under heterotrophic fed-batch fermentation, although its astaxanthin content is much lower (~0.1-0.5% DW). While H. pluvialis remains the benchmark for natural astaxanthin due to its exceptionally high cellular content, its thick cell wall, slow growth, and strict phototrophic requirements impose major cost and operational barriers. In contrast, C. zofingiensis exhibits rapid and flexible growth under heterotrophic, mixotrophic, or phototrophic conditions and can achieve ultrahigh biomass in fermentation, though its ketocarotenoid flux and astaxanthin accumulation remain comparatively limited. Meanwhile, a rapidly growing patent landscape demonstrates global technological competition, with major portfolios emerging in China, the United States, and Europe, spanning chemical synthesis, microbial fermentation, algal metabolic engineering, and high-density cultivation methods. These patents reveal clear innovation trends-ranging from solvent-free green synthesis routes to engineered microalgae and yeast chassis for enhanced astaxanthin production-which increasingly shape industrial development strategies. By synthesizing recent advances in metabolic engineering, two-stage cultivation, and green extraction technologies, this review identifies key knowledge gaps and outlines a practical roadmap for developing next-generation astaxanthin biorefineries, with an emphasis on scalable production and future integration into broader biorefinery frameworks. The findings aim to guide future research and provide actionable insights for scaling sustainable, cost-effective production of natural astaxanthin.

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, continues to pose major global health challenges despite extensive vaccination efforts. Variant escape, waning immunity, and reduced vaccine efficacy in immunocompromised populations underscore the urgent need for complementary antiviral therapeutics. Here, we report the design, synthesis, and biological evaluation of precision-engineered dermatan sulfate (DS)-mimetic glycopolymers as multi-targeted inhibitors of SARS-CoV-2. Guided by molecular docking and virtual screening, sulfation at the C2 and C4 positions of iduronic acid was identified as critical for binding to the viral spike protein and inhibiting host and viral enzymes, including heparanase (HPSE) and main protease (M^pro). Chemically synthesized DS disaccharides were covalently grafted onto polymer scaffolds via a post-modification strategy, yielding glycopolymers with well-defined assembly that form uniform nanoparticles under physiological conditions. Surface plasmon resonance and pseudovirus assays revealed strong binding to the viral spike protein (K_D ≈ 177 nM), potent viral neutralization, and minimal cytotoxicity. Cellular uptake studies further demonstrated efficient internalization of nanoparticles and intracellular inhibition of HPSE and M^pro. These results establish a modular, non-anticoagulant, and glycosaminoglycan-mimetic platform for the development of broad-spectrum antiviral agents to complement vaccination and enhance preparedness against emerging coronavirus variants.

The biomass and lipid production responses of the psychrophilic marine thraustochytrid Thraustochytrium sp. RT2316-16 were assessed in chemically defined media comprising glucose, up to 17 amino acids and up to 9 B-vitamins and mineral salts. Compared to the control medium with all amino acids and B-vitamins (biomass concentration: 7.1 ± 0.1 g L^-1; total lipid content: 30.4 ± 0.5% of the DW), the growth of RT2316-16 was reduced by more than 50% in the medium that lacked cyanocobalamin or pyridoxamine. The total lipid content of the biomass grown in the absence of vitamins was 63% lower than in the biomass produced in the control medium. The composition of the B-vitamin mixture modulated the fatty acid composition, an effect that may have been related to the availability of dissolved oxygen. In bioreactor culture with the dissolved oxygen level controlled to ≥10% of air saturation, the microorganism consumed all 17 amino acids; 8 of the amino acids were fully consumed within a 0-33 h period, in which the specific growth rate was 0.065 h^-1. Under these culture conditions, the sum of eicosapentaenoic acid and docosahexaenoic acid in the total fatty acid content rose from 15% (at time 0) to 54% (after 95 h). A medium that contained the 9 amino acids that were not preferentially consumed favored the accumulation of total lipids, but reduced biomass growth.

The past five years have marked a significant evolution in terpenoid natural product research, with direct implications for marine drug discovery [...].

Marine algae are a prolific bioactive peptide source with a broad pharmacological potential. We characterized MP28, a cationic peptide isolated from the green alga Bryopsis plumosa. Structural modeling indicated a predominantly amphipathic α-helix (residues 3-16) flanked by flexible termini and stabilized by intramolecular disulfide bonds, a motif typical of membrane-active anticancer peptides. Functionally, MP28 demonstrated potent activity against non-small-cell lung cancer cell lines (A549, H460, H1299) without affecting non-tumorigenic lung fibroblasts (MRC-5). In vitro, MP28 decreased cell viability and clonogenic growth and suppressed migration and invasion in a dose-dependent manner. Flow cytometry revealed increased early/late apoptotic fractions, accompanied by caspase-9 activation, consistent with engagement of the intrinsic apoptotic pathway. In a mouse xenograft model, MP28 treatment significantly reduced tumor size compared with that of controls. Collectively, MP28 may be a potent anticancer peptide that exhibits selective cytotoxicity and low toxicity toward normal cells.

Cold-active lipolytic enzymes enable low-temperature biocatalysis, but remain underexplored in Antarctic actinomycetes. Here, we report the discovery and first-step characterization of a CALB-like cold-active lipolytic enzyme (PanLip) from Pseudonocardia antarctica. Sequence and structure analyses revealed a canonical α/β-hydrolase fold with a conserved Ser-Asp-His triad and short helical elements around the pocket reminiscent of CALB's α5/α10 lid. Mature PanLip was expressed primarily as inclusion bodies in E. coli; an N-terminally truncation (PanLipΔN) improved solubility and PanLipΔN was purified by Ni-NTA. Far-UV CD confirmed a folded α/β architecture. PanLipΔN favored short-chain substrates (p-NPA, k_cat/K_M = 2.4 × 10⁵ M^-1·s^-1) but also showed measurable hydrolytic activity toward natural triglycerides, consistently with a lipase-family esterase. The enzyme showed an activity optimum near 25 °C and pH 8.0. The enzyme tolerated low salt (maximal at 0.1 M NaCl), mild glycerol, and selected organic solvents (notably n-hexane), but was inhibited by high salt, Triton X-100, and SDS. AlphaFold predicted high local confidence for the catalytic core; DALI placed PanLip closest to fungal lipases (AFLB/CALB). Temperature-series MD and CABS-flex indicated enhanced surface breathing and flexible segments adjacent to the active site-including a region topologically matching CALB α10-supporting a flexibility-assisted access mechanism at low temperature. Structure-based MSAs did not support a cold adaptation role for the reported VDLPGRS motif. Taken together, these findings position PanLip as a promising cold-active catalyst with CALB-like access control and potential for low-temperature biocatalysis.