{"title":"Effects of Salinity on the Growth Performance and Docosahexaenoic Acid Positional Distribution in Triacylglycerols of the Newly Isolated <i>Schizochytrium</i> sp. FJ-1.","authors":"Sitong Ye, Xiaonan Wang, Youcai Zhou, Xuehua Xiao, Pingying Liu, Chengdeng Chi, Peipei Sun, Mingmin Zheng, Bilian Chen, Ruoyu Mao, Yongjin He","doi":"10.3390/md23070260","DOIUrl":"10.3390/md23070260","url":null,"abstract":"<p><p><i>Schizochytrium</i>-derived omega-3 polyunsaturated fatty acids (e.g., docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) are proven to be health-beneficial bioactive substances that have been widely applied in the pharmaceutical, nutraceutical, and food industries. In this work, the newly isolated <i>Schizochytrium</i> sp. FJ-1 strain was selected to investigate the effects of salinity on the growth performance, lipid production, DHA yield, and positional distribution of triacylglycerols (TAGs). In addition, <i>Schizochytrium</i> sp. 20888 was used as a control strain. The obtained results showed that <i>Schizochytrium</i> sp. FJ-1 could grow with a low biomass in the absence of sea salt; however, <i>Schizochytrium</i> sp. 20888 did not grow in the medium without sea salt. Moreover, <i>Schizochytrium</i> sp. FJ-1 achieved the highest biomass in 10‱ salinity, whilst <i>Schizochytrium</i> sp. 20888 attained the greatest biomass in 40‱ salinity. In terms of the total lipid content and TAG fraction percentage, <i>Schizochytrium</i> sp. FJ-1 grown in 5-20‱ salinity had high total lipid contents (57.04-60.02%), with TAGs accounting for over 90% of the lipid fraction. The highest DHA contents for total lipids (41.38%) and TAGs (40.18%) were obtained when <i>Schizochytrium</i> sp. FJ-1 was grown under 10‱ salinity conditions. Additionally, under the same culture condition, EPA contents of lipids and TAGs were significantly higher for <i>Schizochytrium</i> sp. FJ-1 compared with <i>Schizochytrium</i> sp. 20888. Furthermore, nuclear magnetic resonance analysis found that the salinity level had a distinct impact on the positional distribution of DHA in TAGs in these two <i>Schizochytrium</i> strains. <i>Schizochytrium</i> sp. FJ-1 grown under 40‱ salinity conditions produced TAGs with the greatest percentage of <i>sn</i>-2 DHA (81.24%). The percentages were higher than those found for the other groups of this microalga and <i>Schizochytrium</i> sp. 20888. Taken together, <i>Schizochytrium</i> sp. FJ-1 could be a potential candidate to produce highly valued DHA lipids or TAG bioproducts by regulating salinity.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 7","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12299965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marine DrugsPub Date : 2025-06-23DOI: 10.3390/md23070262
Lamiaa A Shaala, Diaa T A Youssef, Hadeel Almagthali, Ameen M Almohammadi, Wafaa T Arab, Torki Alzughaibi, Noor M Bataweel, Reham S Ibrahim
{"title":"Didemnosides A and B: Antiproliferative Nucleosides from the Red Sea Marine Tunicate <i>Didemnum</i> Species.","authors":"Lamiaa A Shaala, Diaa T A Youssef, Hadeel Almagthali, Ameen M Almohammadi, Wafaa T Arab, Torki Alzughaibi, Noor M Bataweel, Reham S Ibrahim","doi":"10.3390/md23070262","DOIUrl":"10.3390/md23070262","url":null,"abstract":"<p><p>Marine tunicates are a very attractive and abundant source of secondary metabolites with chemical diversity and biological activity. Fractionation and purification of the organic extract of the Red Sea tunicate <i>Didemnum</i> species resulted in the isolation and identification of three new compounds, didemnosides A and B (<b>1</b> and <b>2</b>) and 1,1',3,3'-bisuracil (<b>3</b>), together with thymidine (<b>4</b>), 2'-deoxyuridine (<b>5</b>), homarine (<b>6</b>), and acetamide (<b>7</b>). Planar structures of the compounds were explained through analyses of their 1D (<sup>1</sup>H and <sup>13</sup>C) and 2D (<sup>1</sup>H-<sup>1</sup>H COSY, HSQC, and HMBC) NMR spectra and high-resolution mass spectral determinations. Compound <b>1</b> exhibited the highest growth inhibition toward the MCF-7 cancer cell line with IC<sub>50</sub> values of 0.597 μM, while other compounds were inactive (≥50 μM) against this cell line. On the other hand, compounds <b>1</b>, <b>2</b>, and <b>4</b>-<b>7</b> moderately inhibited SW-1222 and PC-3 cells with IC<sub>50</sub> values ranging between 5.25 and 9.36 μM. Molecular docking analyses of the top three active compounds on each tested cell line exposed stable interactions into the active pockets of estrogen receptor alpha (ESR1), human topoisomerase II alpha (TOP2A), and cyclin-dependent kinase 5 (CDK5) which are contemplated as essential targets in cancer treatments. Thus, compound <b>1</b> represents a scaffold for the development of more effective anticancer drugs.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 7","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12298903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marine DrugsPub Date : 2025-06-23DOI: 10.3390/md23070261
Zhaochao Wang, Juanjuan Yu, Chenjie Wang, Yi Hua, Hong Wang, Jianwei Chen
{"title":"The Deep Mining Era: Genomic, Metabolomic, and Integrative Approaches to Microbial Natural Products from 2018 to 2024.","authors":"Zhaochao Wang, Juanjuan Yu, Chenjie Wang, Yi Hua, Hong Wang, Jianwei Chen","doi":"10.3390/md23070261","DOIUrl":"10.3390/md23070261","url":null,"abstract":"<p><p>Over the past decade, microbial natural products research has witnessed a transformative \"deep-mining era\" driven by key technological advances such as high-throughput sequencing (e.g., PacBio HiFi), ultra-sensitive HRMS (resolution ≥ 100,000), and multi-omics synergy. These innovations have shifted discovery from serendipitous isolation to data-driven, targeted mining. These innovations have transitioned discovery from serendipitous isolation to data-driven targeted mining. Genome mining pipelines (e.g., antiSMASH 7.0 and DeepBGC) can now systematically discover hidden biosynthetic gene clusters (BGCs), especially in under-explored taxa. Metabolomics has achieved unprecedented accuracy, enabling researchers to target novel compounds in complex extracts. Integrated strategies-combining genomic prediction, metabolomics analysis, and experimental validation-constitute new paradigms of current \"deep mining\". This review provides a systematic overview of 185 novel microbial natural products discovered between 2018 and 2024, and dissects how these technological leaps have reshaped the discovery paradigm from traditional isolation to data-driven mining.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 7","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12299652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marine DrugsPub Date : 2025-06-23DOI: 10.3390/md23070263
Cristina Blanco-Llamero, Paz García-García, Francisco Javier Señoráns
{"title":"An Integrated Biorefinery Process to Revalorize Marine Biomass from the Microalga <i>Nannochloropsis gaditana</i> Using Pressurized Green Solvents.","authors":"Cristina Blanco-Llamero, Paz García-García, Francisco Javier Señoráns","doi":"10.3390/md23070263","DOIUrl":"10.3390/md23070263","url":null,"abstract":"<p><p>Biorefinery is gaining attention as a promising approach to valorize natural resources and promote a circular bioeconomy. This study aimed to recover high-value molecules, such as xanthophylls and polar lipids with nutraceutical applications, through enzymatic pretreatment and sequential pressurized liquid extraction (PLEseq), by reusing the residual biomass of <i>Nannochloropsis gaditana</i> after each processing step. Remarkably, pure glycolipids (102.95 ± 1.10 mg g<sup>-1</sup> dry weight) were obtained immediately after enzymatic pretreatment, facilitating their easy recovery. Furthermore, two alternative sequential extraction processes were successfully developed, using ethanol and water as green solvents at varying temperatures and in different orders. The most effective PLEseq conditions yielded up to 48 mg mL<sup>-1</sup> of carbohydrates using water at 50 °C, and up to 44 mg mL<sup>-1</sup> of proteins via subcritical water extraction at 100 °C, prior to conventional lipid extraction with ethanol to produce various concentrated extracts. In the inverted PLEseq process-starting with ethanol extraction followed by successive water washes-isolated and purified fractions of lutein and astaxanthin were obtained, contributing to the complete depletion of the residual biomass. Overall, the development of an integrated and sequential biorefinery protocol that enables the extraction of multiple high-value compounds holds significant potential for application in the food industry.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 7","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12298598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Comparative Study of the Phytochemical Composition, Antioxidant Properties, and In Vitro Anti-Diabetic Efficacy of Different Extracts of <i>Caulerpa prolifera</i>.","authors":"Safae Ouahabi, Nour Elhouda Daoudi, Mohamed Chebaibi, Ibrahim Mssillou, Ilyesse Rahhou, Mohamed Bnouham, Belkheir Hammouti, Marie-Laure Fauconnier, Alicia Ayerdi Gotor, Larbi Rhazi, Mohammed Ramdani","doi":"10.3390/md23070259","DOIUrl":"10.3390/md23070259","url":null,"abstract":"<p><p>The Moroccan coastline has been the focus of attention for researchers studying the national algal flora, with the aim of preserving these invaluable natural resources. Since the year 2000, these resources have stimulated great interest in the creation of new drugs, as well as their integration into food supplements and foods. Therefore, this study aims to explore the phytochemistry of a series of extracts derived from <i>Caulerpa prolifera</i>. To ensure better extraction of the various metabolites present, two extraction methods, namely maceration and the Soxhlet method, were employed using solvents of varying polarity (hexane, ethyl acetate, methanol, and water). The chemical composition of the extracts was analyzed using GC-MS for fatty acids and HPLC-DAD for phenolic compounds. Antioxidant activity was evaluated using DPPH and β-carotene bleaching assays, while antidiabetic potential was assessed by in vitro inhibition of α-amylase and α-glucosidase. In addition, Molecular docking models were employed to assess the interaction between the bioactive molecules and the human pancreatic α-amylase and α-glucosidase enzymes. Vanillin, p-coumaric acid, sinapic acid, 7,3',4'-flavon-3-ol, and kaempferol were the most abundant phenolic compounds. Anti-diabetic and antioxidant effects were highly significant.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 7","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12298174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Searching for Paralytic Toxin, Tetrodotoxin, in Swedish Bivalve Shellfish.","authors":"Aida Zuberovic Muratovic, Shyamraj Dharavath, Jonas Bergquist, Malin Persson, Elin Renborg, Heidi Pekar, Mirjam Klijnstra","doi":"10.3390/md23060257","DOIUrl":"10.3390/md23060257","url":null,"abstract":"<p><p>Tetrodotoxin (TTX), earlier known as a tropical paralytic neurotoxin from pufferfish poisoning, has increasingly been occurring in edible marine species, including filter-feeding bivalves, from relatively cold marine waters of some European countries. The defined conditions that promote the production of TTX, its origin or the processes of its accumulation in seafood are still not clarified. Recent studies in temperate waters show, however, that the accumulation of quantifiable levels of TTX in bivalves appears to be influenced by seawater temperature (>15 °C), which indicates a seasonal occurrence at these latitudes. Uncertainties still remain regarding how seawater temperature interacts with other climate and environmental factors or organisms in the marine ecosystem to result in detectable levels of TTX in shellfish. Knowledge of the occurrence and distribution of TTX in the marine environment where the edible bivalves grow is important for maintaining seafood safety, as the toxin is heat-stable and remains potent even after cooking. Therefore, in this study, 264 bivalve samples collected in 2019 and 2021 from 17 sites along the Swedish west coast were analyzed with LC-MS/MS to search for TTX. The study explores the hypothesis of TTX presence in Swedish marine waters, outlines the sample screening strategy and objectives, and reports no evidence of TTX presence in Swedish bivalve shellfish (≥7.8 µg/kg) based on the analyzed samples and the time periods in which the studied samples were collected.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12194443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marine DrugsPub Date : 2025-06-19DOI: 10.3390/md23060258
Yimao Wu, Xiaoyan Chen, Zichang Chen, Yunqi Ma
{"title":"Targeting Ferroptosis in Tumors: Novel Marine-Derived Compounds as Regulators of Lipid Peroxidation and GPX4 Signaling.","authors":"Yimao Wu, Xiaoyan Chen, Zichang Chen, Yunqi Ma","doi":"10.3390/md23060258","DOIUrl":"10.3390/md23060258","url":null,"abstract":"<p><p>This article reviews the mechanisms by which marine natural products regulate ferroptosis and their potential applications in tumor therapy. Ferroptosis is a form of programmed cell death driven by iron-dependent lipid peroxidation, characterized primarily by the accumulation of lipid peroxides and the failure of antioxidant defense systems. Due to their unique chemical structural diversity, marine natural products demonstrate significant advantages in regulating the ferroptosis pathway. Studies showed that marine compounds target key molecules such as glutathione peroxidase 4 (GPX4) and long-chain acyl-CoA synthetase 4 (ACSL4(a)) ACSL4(1) to modulate lipid peroxidation and iron metabolism, inducing ferroptosis in tumor cells and reshaping the tumor microenvironment (TME). In addition, marine compounds can enhance anti-tumor effects by activating immune responses. Although marine compounds hold great potential in regulating ferroptosis, their clinical translation faces challenges such as low bioavailability and tumor type dependency. Future research needs to integrate multi-omics techniques to further analyze the mechanisms of marine compounds and develop precision therapeutic strategies based on marine compounds to overcome the bottlenecks in ferroptosis therapy.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12194754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marine DrugsPub Date : 2025-06-16DOI: 10.3390/md23060256
Fengwei Yin, Xiaolong Sun, Xi Luo, Weilong Zheng, Longfei Yin, Yingying Zhang, Yongqian Fu
{"title":"A Review on Marine Microbial Docosahexaenoic Acid Production Through Circular Economy, Fermentation Engineering, and Antioxidant Technology.","authors":"Fengwei Yin, Xiaolong Sun, Xi Luo, Weilong Zheng, Longfei Yin, Yingying Zhang, Yongqian Fu","doi":"10.3390/md23060256","DOIUrl":"10.3390/md23060256","url":null,"abstract":"<p><p>Marine microbial-derived docosahexaenoic acid (DHA) has garnered significant attention as a sustainable and health-promoting alternative to fish oil-derived DHA. However, its industrial production from marine heterotrophic microorganisms faces challenges related to high costs and suboptimal oil quality, which hinder its broader application. This review focuses on recent strategies aimed at achieving low-cost and high-quality marine microbial DHA production, emphasizing heterotrophic systems that dominate commercial supply. Key aspects include: Fermentation optimization using waste-derived feedstocks and bioprocess engineering to enhance DHA yields; Critical refining techniques-including degumming, neutralization, decolorization, and deodorization-are analyzed for improving DHA oil purity and quality, with emphasis on process optimization to adapt to the unique biochemical properties of microbial-derived oils. Additionally, strategies for oxidative stabilization, such as antioxidant protection, are discussed to extend the shelf life and preserve the nutritional value of marine microbial DHA oil. By integrating techno-economic and biochemical perspectives, this work outlines a holistic framework to guide the industrial optimization of marine microbial-sourced DHA oil production, addressing cost and quality challenges to facilitate its large-scale application as functional foods and nutraceuticals, thereby reducing reliance on marine resources and advancing sustainable omega-3 production.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12194448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bioactive Polyketides from <i>Amphidinium</i> spp.: An In-Depth Review of Biosynthesis, Applications, and Current Research Trends.","authors":"Noemi Russo, Giulia Quaini, Marcello Ziaco, Daniela Castiglia, Alessandra Ruggiero, Vincenzo D'Amelia, Concetta Di Napoli, Sergio Esposito, Angelo Fontana, Genoveffa Nuzzo, Simone Landi","doi":"10.3390/md23060255","DOIUrl":"10.3390/md23060255","url":null,"abstract":"<p><p>Polyketides (PKs) are a widespread class of secondary metabolites with recognised pharmacological properties. These molecules are abundantly produced in the marine environment, especially by dinoflagellate-photosynthetic organisms able to produce several PKs, including neurotoxins, cytotoxins, and immunomodulating agents. The biosynthesis of these compounds is driven by a conserved enzymatic process involving polyketide synthase complexes. Different genera of dinoflagellates produce PKs. Among them, dinoflagellates of the genus <i>Amphidinium</i> are of particular interest due to its ability to produce the following two major families of PKs: amphidinolides and amphidinols. These compounds display remarkable biological activities, including anticancer, antimicrobial, and antifungal effects, making them attractive targets for pharmaceutical research and development. However, the natural yield of <i>Amphidinium</i>-derived polyketides (APKs) is generally low, limiting their potential for sustainable molecular farming. This challenge has prompted interest in developing biotechnological strategies to enhance their production. This review aims to define the current state of studies about APKs, starting from their initial discoveries to the recent understanding of their biosynthetic pathways. Additionally, it summarizes the structures of compounds discovered, highlights their biotechnological potential, and discusses novel trends in their production.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12194139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the Catalytic Mechanisms of a Newly Identified Salt-Activated Alginate Lyase from <i>Pseudoalteromonas carrageenovora</i> ASY5.","authors":"Xiaoyan Zhuang, Chao Jiao, Zewang Guo, Qiong Xiao, Jun Chen, Fuquan Chen, Qiuming Yang, Yi Ru, Huifen Weng, Siyuan Wang, Anfeng Xiao, Yonghui Zhang","doi":"10.3390/md23060254","DOIUrl":"10.3390/md23060254","url":null,"abstract":"<p><p>Alginate lyases are critical enzymes in hydrolyzing alginate into alginate oligosaccharides (AOS), which are bioactive compounds known for their antioxidant properties and ability to lower serum glucose and lipid concentrations. However, elucidating catalytic mechanisms and discovering enzymes with enhanced catalytic efficiency remain long-term challenges. Here, we report AlgL2491, a novel bifunctional and cold-adapted alginate lyase from <i>Pseudoalteromonas carrageenovora</i> ASY5, belonging to the polysaccharide lyase family 18. This enzyme uniquely cleaves both polyguluronic (polyG) and polymannuronic (polyM), predominantly releasing disaccharides, trisaccharides, and tetrasaccharides after 12 h of hydrolysis. The enzyme achieves peak catalytic efficiency at 35 °C and pH 7.5, with activity increasing 5.5-fold in 0.5 M of NaCl. Molecular dynamics simulations demonstrate that salt ions enhance structural stability by minimizing conformational fluctuations and strengthening interdomain interactions, providing mechanistic insights into its salt-activated behavior. The alginate oligosaccharides (AOS) exhibit excellent free radical-scavenging activities of 86.79 ± 0.31%, 83.42 ± 0.18%, and 71.28 ± 2.27% toward hydroxyl, ABTS, and DPPH radicals, with IC50 values of 8.8, 6.74, and 9.71 mg/mL, respectively. These findings not only reveal the salt-activation mechanism of AlgL2491 and highlight the potential value of its hydrolysate in antioxidant activity but also provide a sustainable industrial solution in industrial-scale AOS production directly from marine biomass, eliminating the need for energy-intensive desalination of alginate, which may inform future biocatalyst design for marine polysaccharide valorization.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 6","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12193947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}