Marine Drugs最新文献

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.

The rapid spread of the invasive brown macroalga Rugulopteryx okamurae has caused severe ecological and economic damage along the European coasts. Efforts to mitigate its impact have been largely ineffective, highlighting the need for alternative strategies to valorise this invasive species. This study explores the use of R. okamurae aqueous extract (RO extract) as a natural reducing and stabilizing agent for the green synthesis of gold (Au@RO), silver (Ag@RO), and platinum (Pt@RO) nanoparticles. The synthesized nanoparticles were extensively characterized using ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), X-ray diffraction (XRD), zeta potential analysis, and Fourier-transform infrared spectroscopy (FTIR). The results confirmed the successful formation of spherical and stable nanoparticles. Furthermore, the antioxidant activity of the RO extract was determined before and after the synthesis of the nanoparticles by the determination of the reducing power, total phenolic content and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity. Notably, Pt@RO showed the highest enhancement in antioxidant activity among the nanoparticles synthesized. The findings demonstrate that R. okamurae can be repurposed as a valuable bioresource for the environmentally friendly production of metal nanoparticles with promising applications.

The Isles of Scilly are an archipelago of islands in the far southwest of the UK which contain numerous beds of wild bivalve molluscs which are recreationally harvested for local consumption. However, the islands have never previously been assessed for the presence of harmful algae and their shellfish toxin metabolites which can cause serious human health impacts. This study sought to address these knowledge gaps through the analysis of seawater and shellfish tissues for microalgae and toxins utilizing portable and lab-based microscopy, nanopore sequencing, chemical analysis and immunoassay kits. The study design was affected by the national COVID-19 lockdown which enforced implementation of citizen-led sampling and in-field microscopy. Microscopy and sequencing approaches led to the confirmation of multiple HAB species of concern, including those potentially responsible for production of neurotoxic and diarrhetic shellfish toxins. A portable microscope was successfully utilized in the field for recognition of microalgae and for early warning of potential shellfish toxicity events. Chemical analysis of cockle, clam and mussel samples confirmed the detection of paralytic, diarrhetic and amnesic shellfish toxins, with an unusual okadaic acid group toxin profile reaching a maximum toxicity of approximately half the regulatory limit as defined by EU law. The Sensoreal Alert Lateral Flow Assay was used to screen and highlight samples containing higher concentrations of DSP toxins. Furthermore, Tetrodotoxin was detected for the first time in the UK in cockle and grooved carpet shells. Multiple saxitoxin analogues were also detected in two echinoderm species, with this providing the first ever report of paralytic shellfish toxins in the spiny starfish, Marthasterias glacialis. The toxin profiles in the two species varied significantly with a dominance of GTX4 in Luidia ciliaris as opposed to a dominance of STX in Marthasterias glacialis. Overall, the study showed that a multi-method assessment of a previously unexplored region within the UK territory contained microalgae and toxins of concern to human health, and that a citizen-led programme could be instigated using portable microscopy and rapid toxin testing to assess the early warning for potentially harmful microalgae and toxins in the region, with confirmatory analysis being conducted to establish actual levels of risk for local consumers of seafood.

Four new methionine sulfoxide-containing diketopiperazines, (+)-dysidmetsulfoxide A [(+)-1], (+)-dysidmetsulfoxide B [(+)-2], (+)-dysidmetsulfoxide C [(+)-3] and (-)-dysidmetsulfoxide C [(-)-3], were isolated from the South China Sea sponge Dysidea sp. These compounds represented the first example of diketopiperazines possessing the unit of methionine sulfoxide (MetO) isolated from marine sponges. As it was difficult to determine the configuration of chiral sulfur atom in the thionyl group, the structures with absolute configurations of these compounds were elucidated by spectroscopic analyses and total synthesis. It was noteworthy that the purchased synthetic precursors, Fmoc-L- and Fmoc-D-MetO, were mixtures of epimers, respectively, due to the stereogenic sulfur atom in MetO, which were separated to prepare the optically pure isomers via the method of supercritical fluid chromatography (SFC). In addition, the other four optical isomers [(-)-1, (-)-2, (+)-4 and (-)-4] were also synthesized. Furthermore, (+)-1, (-)-1, (+)-3, (+)-4 and (-)-4 showed potential anti-Parkinson's disease activities in an in vivo zebrafish model.

Astaxanthin is a high-value metabolite with substantial market demand, owing to its potent antioxidant activity and diverse health benefits. Microalgae are considered the primary producers of esterified astaxanthin, yet their industrial-scale cultivation is constrained by low productivity, stress-dependent induction, and challenges in metabolic engineering. This review examines strategies to enhance microalgae-derived esterified astaxanthin production through nanoformulation and modulation of metabolic pathways. We highlight that precise, efficient, and multiplexed genetic modifications of the carotenoid biosynthetic pathway can significantly increase astaxanthin accumulation. Downregulation of competing metabolic routes further improves astaxanthin yields. Additionally, targeted engineering of acyltransferases and lipid metabolism regulators enhances astaxanthin esterification, thereby improving its intracellular stability against oxidative degradation. Modifying lipid metabolism also redirects metabolic fluxes toward altered fatty acid saturation in stored lipids, which increases the bioavailability of esterified astaxanthin. The integration of nanoparticles into cultivation systems represents another promising approach, facilitating improved nutrient delivery and light management, and consequently boosting astaxanthin production. However, the application of genetic engineering and nanotechnology faces challenges such as biosafety legislation, regulatory approval processes, and potential ecological impacts. A synergistic combination of both approaches may help overcome these limitations and maximize astaxanthin production from microalgae.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by cholinergic dysfunction, oxidative/nitrosative stress, and neuroinflammation. Marine green algae Caulerpa racemosa are rich in neuroactive lipids and fatty acid derivatives with reported antioxidant and anti-inflammatory properties. However, their integrated mechanistic potential against AD remains largely underexplored. This study aimed to elucidate the neuroprotective mechanisms of C. racemosa metabolites against AD using integrative metabolomics, network pharmacology, molecular docking, and in vitro validation assays. Untargeted LC-HRMS profiling was performed to identify major metabolites in the ethanolic extract of C. racemosa. Neuroprotective targets were predicted via TargetNet, STRING, and Cytoscape (MCODE, CytoNCA). Functional enrichment was conducted using KEGG, GO (BP, MF, CC), and ClueGO. Molecular docking (CB-Dock2) validated compound-target interactions with ACHE, CHRM1, NOS1, and NOS2. Antioxidant (DPPH) and cholinesterase (AChE/BChE) inhibitory activities were evaluated in vitro. Metabolomic profiling identified lipid-dominant metabolites-oleamide, hexadecanamide, palmitoyl ethanolamide, α-linolenic acid, α-eleostearic acid, and 9-oxo-octadecadienoic acid. Network analysis revealed key AD-related hubs (ACHE, CHRM1, NOS1, NOS2) enriched in cholinergic regulation, arachidonic-acid metabolism, oxidative stress response, and nitric oxide signaling. Docking showed moderate multi-target affinities (-6.0 to -8.4 kcal/mol), with α-linolenic acid, α-eleostearic acid, and oxidized C18 lipids exhibiting the strongest interactions-particularly with ACHE and NOS isoforms. In vitro assays showed moderate antioxidant activity (IC₅₀ = 120.97 ± 10.93 µg/mL) and cholinesterase inhibition (AChE IC₅₀ = 136.48 ± 1.70 µg/mL; BChE IC₅₀ = 145.98 ± 3.28 µg/mL), aligning with predicted multi-target interactions. C. racemosa extract exhibits neuroprotective potential through a synergistic combination of cholinergic modulation, antioxidant activity, NOS-mediated nitrosative stress reduction, and suppression of arachidonic-acid inflammatory pathways. These findings support C. racemosa as a promising marine-derived multi-target candidate for AD intervention, warranting further mechanistic and in vivo evaluation.

Mangrove forests represent a complex ecosystem inhabiting tropical and subtropical intertidal zones, harboring diverse microbial communities including fungi, actinomycetes, bacteria, cyanobacteria, algae, and protozoa. Among these communities, mangrove-derived fungi, as the second-largest ecological group of marine fungi, not only play essential roles in establishing and sustaining this biosphere but also serve as an important source of structurally unique and biologically active secondary metabolites. This review systematically summarizes research progress on metabolites isolated from mangrove-derived fungi and their associated bioactivities over the recent five years (2020-2025). Emphasis is placed on 457 metabolites documented in 97 selected publications, with a focus on the biological activities and distinctive chemical diversity of these secondary metabolites. This review provides an important reference for the research status of secondary metabolites isolated from mangrove-derived fungi and the lead compounds worthy of further development, and reveals that mangrove-derived fungi have important medicinal values and are worthy of further development.