Marine Drugs

15 pages, 3407 KiB

Open AccessArticle

In Vitro In Silico Screening Strategy and Mechanism of Novel Tyrosinase Inhibitory Peptides from Nacre of Hyriopsis cumingii

by Haisheng Lin, Fei Li, Jiaao Kang, Shaohe Xie, Xiaoming Qin, Jialong Gao, Zhongqin Chen, Wenhong Cao, Huina Zheng and Wenkui Song

Mar. Drugs 2024, 22(9), 420; https://doi.org/10.3390/md22090420 (registering DOI) - 15 Sep 2024

Abstract

For thousands of years, pearl and nacre powders have been important traditional Chinese medicines known for their skin whitening effects. To prepare the enzymatic hydrolysates of Hyriopsis cumingii nacre powder (NP-HCH), complex enzymatic hydrolysis by pineapple protease and of neutral protease was carried [...] Read more.

For thousands of years, pearl and nacre powders have been important traditional Chinese medicines known for their skin whitening effects. To prepare the enzymatic hydrolysates of Hyriopsis cumingii nacre powder (NP-HCH), complex enzymatic hydrolysis by pineapple protease and of neutral protease was carried out after the powder was pre-treated with a high-temperature and high-pressure method. The peptides were identified using LC-MS/MS and picked out through molecular docking and molecular dynamics simulations. Subsequently, the tyrosinase inhibitory and antioxidant properties of novel tyrosinase inhibitory peptides were investigated in vitro. In addition, the enzymatic activity of tyrosinase in B16F10 cells as well as melanin content and antioxidant enzyme levels were also examined. The results showed that a tyosinase inhibitory peptide (Tyr-Pro-Asn-Pro-Tyr, YPNPY) with an efficient IC₅₀ value of 0.545 ± 0.028 mM was identified. The in vitro interaction results showed that YPNPY is a reversible competitive inhibitor of tyrosinase, suggesting that it binds to the free enzyme. The B16F10 cell whitening test revealed that YPNPY can reduce the melanin content of B16F10 cells by directly inhibiting the activity of intracellular tyrosinase. Additionally, it indirectly affects melanin production by acting as an antioxidant. These results suggest that YPNPY could be widely used as a tyrosinase inhibitor in whitening foods and drugs. Full article

(This article belongs to the Special Issue Marine Alkaloids: Sources, Discovery, Diversity, and Bioactivities)

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14 pages, 5606 KiB

Open AccessArticle

Enantioselectivity in Vanadium-Dependent Haloperoxidases of Different Marine Sources for Sulfide Oxidation to Sulfoxides

by Yun-Han Zhang, Ya-Ting Zou, Yong-Yi Zeng, Lan Liu and Bi-Shuang Chen

Mar. Drugs 2024, 22(9), 419; https://doi.org/10.3390/md22090419 (registering DOI) - 14 Sep 2024

Abstract

This study explores the reasons behind the variations in the enantioselectivity of the sulfoxidation of methyl phenyl sulfide by marine-derived vanadium-dependent haloperoxidases (VHPOs). Twelve new VHPOs of marine organisms were overexpressed, purified, and tested for their ability to oxidize sulfide. Most of these [...] Read more.

This study explores the reasons behind the variations in the enantioselectivity of the sulfoxidation of methyl phenyl sulfide by marine-derived vanadium-dependent haloperoxidases (VHPOs). Twelve new VHPOs of marine organisms were overexpressed, purified, and tested for their ability to oxidize sulfide. Most of these marine enzymes exhibited nonenantioselective behavior, underscoring the uniqueness of AnVBPO from the brown seaweed Ascophyllum nodosum and CpVBPO from the red seaweed Corallina pilulifera, which produce (R)- and (S)-sulfoxides, respectively. The enantioselective sulfoxidation pathway is likely due to direct oxygen transfer within the VHPO active site. This was demonstrated through molecular docking and molecular dynamics simulations, which revealed differences in the positioning of sulfide within AnVBPO and CpVBPO, thus explaining their distinct enantioselectivities. Nonenantioselective VHPOs probably follow a different oxidation pathway, initiating with sulfide oxidation to form a positively charged radical. Further insights were gained from studying the catalytic effect of VO₄³⁻ on H₂O₂-driven sulfoxidation. This research improves the understanding of VHPO-mediated sulfoxidation and aids in developing biocatalysts for sulfoxide synthesis. Full article

(This article belongs to the Special Issue Advances of Marine-Derived Enzymes)

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20 pages, 4189 KiB

Open AccessArticle

Regulation of Safracin Biosynthesis and Transport in Pseudomonas poae PMA22

by J. Gerardo Hernández Delgado, Miguel G. Acedos, Fernando de la Calle, Pilar Rodríguez, José Luis García and Beatriz Galán

Mar. Drugs 2024, 22(9), 418; https://doi.org/10.3390/md22090418 - 13 Sep 2024

Abstract

Pseudomonas poae PMA22 produces safracins, a family of compounds with potent broad-spectrum anti-bacterial and anti-tumor activities. The safracins’ biosynthetic gene cluster (BGC sac) consists of 11 ORFs organized in two divergent operons (sacABCDEFGHK and sacIJ) that are controlled by P_a [...] Read more.

Pseudomonas poae PMA22 produces safracins, a family of compounds with potent broad-spectrum anti-bacterial and anti-tumor activities. The safracins’ biosynthetic gene cluster (BGC sac) consists of 11 ORFs organized in two divergent operons (sacABCDEFGHK and sacIJ) that are controlled by P_a and P_i promoters. Contiguous to the BGC sac, we have located a gene that encodes a putative global regulator of the LysR family annotated as MexT that was originally described as a transcriptional activator of the MexEF-OprN multidrug efflux pump in Pseudomonas. Through both in vitro and in vivo experiments, we have demonstrated the involvement of the dual regulatory system MexT-MexS on the BGC sac expression acting as an activator and a repressor, respectively. The MexEF-OprN transport system of PMA22, also controlled by MexT, was shown to play a fundamental role in the metabolism of safracin. The overexpression of mexEF-oprN in PMA22 resulted in fourfold higher production levels of safracin. These results illustrate how a pleiotropic regulatory system can be critical to optimizing the production of tailored secondary metabolites, not only through direct interaction with the BGC promoters, but also by controlling their transport. Full article

(This article belongs to the Special Issue From Seaside to Bedside: Dedicated to Professor José María Fernández Sousa-Faro)

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18 pages, 7588 KiB

Open AccessArticle

Optimizing Antioxidant Potential: Factorial Design-Based Formulation of Fucoidan and Gallic Acid-Conjugated Dextran Blends

by Cynthia Haynara Ferreira Silva, Maylla Maria Correia Leite Silva, Weslley Souza Paiva, Mayara Jane Campos de Medeiros, Moacir Fernandes Queiroz, Luciana Duarte Martins Matta, Everaldo Silvino dos Santos and Hugo Alexandre Oliveira Rocha

Mar. Drugs 2024, 22(9), 417; https://doi.org/10.3390/md22090417 - 13 Sep 2024

Abstract

The role of oxidative stress in health and homeostasis has generated interest in the scientific community due to its association with cardiovascular and neurodegenerative diseases, cancer, and other diseases. Therefore, extensive research seeks to identify new exogenous antioxidant compounds for supplementation. Polysaccharides are [...] Read more.

The role of oxidative stress in health and homeostasis has generated interest in the scientific community due to its association with cardiovascular and neurodegenerative diseases, cancer, and other diseases. Therefore, extensive research seeks to identify new exogenous antioxidant compounds for supplementation. Polysaccharides are recognized for their antioxidant properties. However, polysaccharide chemical modifications are often necessary to enhance these properties. Therefore, dextran was conjugated with gallic acid (Dex-Gal) and later combined with fucoidan A (FucA) to formulate blends aimed at achieving superior antioxidant activity compared to individual polysaccharides. A factorial design was employed to combine FucA and Dex-Gal in different proportions, resulting in five blends (BLD1, BLD2, BLD3, BLD4, and BLD5). An analysis of surface graphs from in vitro antioxidant tests, including total antioxidant capacity (TAC), reducing power, and hydroxyl radical scavenging, guided the selection of BLD4 as the optimal formulation. Tests on 3T3 fibroblasts under various conditions of oxidative stress induced by hydrogen peroxide revealed that BLD4 provided enhanced protection compared to its isolated components. The BLD4 formulation, resulting from the combination of Dex-Gal and FucA, showed promise as an antioxidant strategy, outperforming its individual components and suggesting its potential as a supplement to mitigate oxidative stress in adverse health conditions. Full article

(This article belongs to the Special Issue Polysaccharides from Marine Environment)

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80 pages, 28457 KiB

Open AccessReview

A Chemical Toolbox to Unveil Synthetic Nature-Inspired Antifouling (NIAF) Compounds

by Ana Rita Neves, Sara Godinho, Catarina Gonçalves, Ana Sara Gomes, Joana R. Almeida, Madalena Pinto, Emília Sousa and Marta Correia-da-Silva

Mar. Drugs 2024, 22(9), 416; https://doi.org/10.3390/md22090416 - 12 Sep 2024

Abstract

The current scenario of antifouling (AF) strategies to prevent the natural process of marine biofouling is based in the use of antifouling paints containing different active ingredients, believed to be harmful to the marine environment. Compounds called booster biocides are being used with [...] Read more.

The current scenario of antifouling (AF) strategies to prevent the natural process of marine biofouling is based in the use of antifouling paints containing different active ingredients, believed to be harmful to the marine environment. Compounds called booster biocides are being used with copper as an alternative to the traditionally used tributyltin (TBT); however, some of them were recently found to accumulate in coastal waters at levels that are deleterious for marine organisms. More ecological alternatives were pursued, some of them based on the marine organism mechanisms’ production of specialized metabolites with AF activity. However, despite the investment in research on AF natural products and their synthetic analogues, many studies showed that natural AF alternatives do not perform as well as the traditional metal-based ones. In the search for AF agents with better performance and to understand which molecular motifs were responsible for the AF activity of natural compounds, synthetic analogues were produced and investigated for structure–AF activity relationship studies. This review is a comprehensive compilation of AF compounds synthesized in the last two decades with highlights on the data concerning their structure–activity relationship, providing a chemical toolbox for researchers to develop efficient nature-inspired AF agents. Full article

(This article belongs to the Special Issue Marine Natural Products with Antifouling Activity, 3rd Edition)

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20 pages, 7968 KiB

Open AccessArticle

Blood Coagulation Activities and Influence on DNA Condition of Alginate—Calcium Composites Prepared by Freeze-Drying Technique

by Małgorzata Świerczyńska, Paulina Król, César I. Hernández Vázquez, Klaudia Piekarska, Katarzyna Woźniak, Michał Juszczak, Zdzisława Mrozińska and Marcin H. Kudzin

Mar. Drugs 2024, 22(9), 415; https://doi.org/10.3390/md22090415 - 10 Sep 2024

Abstract

The aim of this research was to synthesize and characterize alginate–calcium composites using a freeze-drying method, with a focus on their potential applications in biomedicine. This study specifically explored the biochemical properties of these composites, emphasizing their role in blood coagulation and their [...] Read more.

The aim of this research was to synthesize and characterize alginate–calcium composites using a freeze-drying method, with a focus on their potential applications in biomedicine. This study specifically explored the biochemical properties of these composites, emphasizing their role in blood coagulation and their capacity to interact with DNA. Additionally, the research aimed to assess how the cross-linking process influences the structural and chemical characteristics of the composites. Detailed analyses, including microscopic examination, surface area assessment, and atomic absorption spectrometry, yielded significant results. The objective of this study was to examine the impact of calcium chloride concentration on the calcium content in alginate composites. Specifically, the study assessed how varying concentrations of the cross-linking solution (ranging from 0.5% to 2%) influence the calcium ion saturation within the composites. This investigation is essential for understanding the physicochemical properties of the materials, including calcium content, porosity, and specific surface area. The results are intended to identify the optimal cross-linking conditions that maximize calcium enrichment efficiency while preserving the material’s structural integrity. The study found that higher calcium chloride concentrations in alginate cross-linking improve the formation of a porous structure, enhanced by two-stage freeze-drying. Increased calcium levels led to a larger surface area and pore volume, and significantly higher calcium content. Furthermore, assays of activated partial thromboplastin time (aPTT) showed a reduction in clotting time for alginate composites containing calcium ions, indicating their potential as hemostatic agents. The aPTT test showed shorter clotting times with higher calcium ion concentrations, without enhanced activation of the extrinsic clotting pathway. The developed alginate material with calcium effectively supports hemostasis and reduces the risk of infection. The study also explored the capacity of these composites to interact with and modify the structure of plasmid DNA, underscoring their potential for future biomedical applications. Full article

(This article belongs to the Section Biomaterials of Marine Origin)

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16 pages, 3244 KiB

Open AccessArticle

Genome Analysis of a Potential Novel Vibrio Species Secreting pH- and Thermo-Stable Alginate Lyase and Its Application in Producing Alginate Oligosaccharides

by Ke Bao, Miao Yang, Qianhuan Sun, Kaishan Zhang and Huiqin Huang

Mar. Drugs 2024, 22(9), 414; https://doi.org/10.3390/md22090414 - 10 Sep 2024

Abstract

Alginate lyase is an attractive biocatalyst that can specifically degrade alginate to produce oligosaccharides, showing great potential for industrial and medicinal applications. Herein, an alginate-degrading strain HB236076 was isolated from Sargassum sp. in Qionghai, Hainan, China. The low 16S rRNA gene sequence identity [...] Read more.

Alginate lyase is an attractive biocatalyst that can specifically degrade alginate to produce oligosaccharides, showing great potential for industrial and medicinal applications. Herein, an alginate-degrading strain HB236076 was isolated from Sargassum sp. in Qionghai, Hainan, China. The low 16S rRNA gene sequence identity (<98.4%), ANI value (<71.9%), and dDDH value (<23.9%) clearly indicated that the isolate represented a potential novel species of the genus Vibrio. The genome contained two chromosomes with lengths of 3,007,948 bp and 874,895 bp, respectively, totaling 3,882,843 bp with a G+C content of 46.5%. Among 3482 genes, 3332 protein-coding genes, 116 tRNA, and 34 rRNA sequences were predicted. Analysis of the amino acid sequences showed that the strain encoded 73 carbohydrate-active enzymes (CAZymes), predicting seven PL7 (Alg1–7) and two PL17 family (Alg8, 9) alginate lyases. The extracellular alginate lyase from strain HB236076 showed the maximum activity at 50 °C and pH 7.0, with over 90% activity measured in the range of 30–60 °C and pH 6.0–10.0, exhibiting a wide range of temperature and pH activities. The enzyme also remained at more than 90% of the original activity at a wide pH range (3.0–9.0) and temperature below 50 °C for more than 2 h, demonstrating significant thermal and pH stabilities. Fe²⁺ had a good promoting effect on the alginate lyase activity at 10 mM, increasing by 3.5 times. Thin layer chromatography (TLC) and electrospray ionization mass spectrometry (ESI-MS) analyses suggested that alginate lyase in fermentation broth could catalyze sodium alginate to produce disaccharides and trisaccharides, which showed antimicrobial activity against Shigella dysenteriae, Aeromonas hydrophila, Staphylococcus aureus, Streptococcus agalactiae, and Escherichia coli. This research provided extended insights into the production mechanism of alginate lyase from Vibrio sp. HB236076, which was beneficial for further application in the preparation of pH-stable and thermo-stable alginate lyase and alginate oligosaccharides. Full article

(This article belongs to the Special Issue Marine Functional Carbohydrates: Enzymatic Manufacturing and Activity Evaluation)

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20 pages, 849 KiB

Open AccessArticle

pH-Dependent Extraction of Antioxidant Peptides from Red Seaweed Palmaria palmata: A Sequential Approach

by Sakhi Ghelichi, Ann-Dorit Moltke Sørensen, Grazielle Náthia-Neves and Charlotte Jacobsen

Mar. Drugs 2024, 22(9), 413; https://doi.org/10.3390/md22090413 - 10 Sep 2024

Abstract

This study employed a diverse approach to extract antioxidant peptides from red seaweed Palmaria palmata, recognized for its comparatively high protein content. Initially, an aqueous extraction of the entire seaweed was performed, followed by enzymatic hydrolysis of the solid residues prepared from [...] Read more.

This study employed a diverse approach to extract antioxidant peptides from red seaweed Palmaria palmata, recognized for its comparatively high protein content. Initially, an aqueous extraction of the entire seaweed was performed, followed by enzymatic hydrolysis of the solid residues prepared from the first step. The effects of three different pH levels (3, 6, and 9) during the aqueous extraction were also examined. Results indicated that the solid fraction from the sequential extraction process contained significantly higher levels of proteins and amino acids than other fractions (p < 0.05). Furthermore, the solid fractions (IC₅₀ ranging from 2.29 to 8.15 mg.mL⁻¹) demonstrated significantly greater free radical scavengers than the liquid fractions (IC₅₀ ranging from 9.03 to 10.41 mg.mL⁻¹ or not obtained at the highest concentration tested) at both stages of extraction (p < 0.05). Among the solid fractions, those produced fractions under alkaline conditions were less effective in radical scavenging than the produced fractions under acidic or neutral conditions. The fractions with most effective metal ion chelating activity were the solid fractions from the enzymatic stage, particularly at pH 3 (IC₅₀ = 0.63 ± 0.04 mg.mL⁻¹) and pH 6 (IC₅₀ = 0.89 ± 0.07 mg.mL⁻¹), which were significantly more effective than those from the initial extraction stage (p < 0.05). Despite no significant difference in the total phenolic content between these solid fractions and their corresponding liquid fractions (3.79 ± 0.05 vs. 3.48 ± 0.02 mg.mL⁻¹ at pH 3 and 2.43 ± 0.22 vs. 2.51 ± 0.00 mg.mL⁻¹ at pH 6) (p > 0.05), the observed antioxidant properties may be attributed to bioactive amino acids such as histidine, glutamic acid, aspartic acid, tyrosine, and methionine, either as free amino acids or within proteins and peptides. Full article

(This article belongs to the Special Issue Isolation, Identification and Applications of Marine Source Polysaccharides and Peptides—2nd Edition)

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14 pages, 4314 KiB

Open AccessArticle

Screening of Lipid-Reducing Activity and Cytotoxicity of the Exometabolome from Cyanobacteria

by Rúben Luz, Rita Cordeiro, Vítor Gonçalves, Vitor Vasconcelos and Ralph Urbatzka

Mar. Drugs 2024, 22(9), 412; https://doi.org/10.3390/md22090412 - 10 Sep 2024

Abstract

Cyanobacteria are rich producers of secondary metabolites, excreting some of these to the culture media. However, the exometabolome of cyanobacteria has been poorly studied, and few studies have dwelled on its characterization and bioactivity assessment. In this work, exometabolomes of 56 cyanobacterial strains [...] Read more.

Cyanobacteria are rich producers of secondary metabolites, excreting some of these to the culture media. However, the exometabolome of cyanobacteria has been poorly studied, and few studies have dwelled on its characterization and bioactivity assessment. In this work, exometabolomes of 56 cyanobacterial strains were characterized by HR-ESI-LC-MS/MS. Cytotoxicity was assessed on two carcinoma cell lines, HepG2 and HCT116, while the reduction in lipids was tested in zebrafish larvae and in a steatosis model with fatty acid-overloaded human liver cells. The exometabolome analysis using GNPS revealed many complex clusters of unique compounds in several strains, with no identifications in public databases. Three strains reduced viability in HCT116 cells, namely Tolypotrichaceae BACA0428 (30.45%), Aphanizomenonaceae BACA0025 (40.84%), and Microchaetaceae BACA0110 (46.61%). Lipid reduction in zebrafish larvae was only observed by exposure to Dulcicalothrix sp. BACA0344 (60%). The feature-based molecular network shows that this bioactivity was highly correlated with two flavanones, a compound class described in the literature to have lipid reduction activity. The exometabolome characterization of cyanobacteria strains revealed a high chemodiversity, which supports it as a source for novel bioactive compounds, despite most of the time being overlooked. Full article

(This article belongs to the Collection Bioactive Compounds from Marine Plankton)

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23 pages, 2764 KiB

Open AccessReview

Enzymes from Fishery and Aquaculture Waste: Research Trends in the Era of Artificial Intelligence and Circular Bio-Economy

by Zied Khiari

Mar. Drugs 2024, 22(9), 411; https://doi.org/10.3390/md22090411 - 10 Sep 2024

Abstract

In the era of the blue bio-economy, which promotes the sustainable utilization and exploitation of marine resources for economic growth and development, the fisheries and aquaculture industries still face huge sustainability issues. One of the major challenges of these industries is associated with [...] Read more.

In the era of the blue bio-economy, which promotes the sustainable utilization and exploitation of marine resources for economic growth and development, the fisheries and aquaculture industries still face huge sustainability issues. One of the major challenges of these industries is associated with the generation and management of wastes, which pose a serious threat to human health and the environment if not properly treated. In the best-case scenario, fishery and aquaculture waste is processed into low-value commodities such as fishmeal and fish oil. However, this renewable organic biomass contains a number of highly valuable bioproducts, including enzymes, bioactive peptides, as well as functional proteins and polysaccharides. Marine-derived enzymes are known to have unique physical, chemical and catalytic characteristics and are reported to be superior to those from plant and animal origins. Moreover, it has been established that enzymes from marine species possess cold-adapted properties, which makes them interesting from technological, economic and sustainability points of view. Therefore, this review centers around enzymes from fishery and aquaculture waste, with a special focus on proteases, lipases, carbohydrases, chitinases and transglutaminases. Additionally, the use of fishery and aquaculture waste as a substrate for the production of industrially relevant microbial enzymes is discussed. The application of emerging technologies (i.e., artificial intelligence and machine learning) in microbial enzyme production is also presented. Full article

(This article belongs to the Special Issue Enzymes from Marine By-Products and Wastes)

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15 pages, 6260 KiB

Open AccessArticle

Altechromone A Ameliorates Inflammatory Bowel Disease by Inhibiting NF-κB and NLRP3 Pathways

by Lei Li, Jing Huang, Lixin Feng, Liyan Xu, Houwen Lin, Kechun Liu, Xiaobin Li and Rongchun Wang

Mar. Drugs 2024, 22(9), 410; https://doi.org/10.3390/md22090410 - 9 Sep 2024

Abstract

Altechromone A, also known as 2,5-dimethyl-7-hydroxychromone, is a hydroxyketone containing one hydroxyl and one ketone group. In this study, we isolated Altechromone A from the marine-derived fungus Penicillium Chrysogenum (XY-14-0-4). Previous reports show that Altechromone A has various activities including tumor suppression, antibacterial, [...] Read more.

Altechromone A, also known as 2,5-dimethyl-7-hydroxychromone, is a hydroxyketone containing one hydroxyl and one ketone group. In this study, we isolated Altechromone A from the marine-derived fungus Penicillium Chrysogenum (XY-14-0-4). Previous reports show that Altechromone A has various activities including tumor suppression, antibacterial, and antiviral activities. However, there is no study about its anti-inflammatory activity in inflammatory bowel disease (IBD). Here, we assess the anti-inflammatory activity, especially in IBD, and its potential mechanism using the zebrafish model. Our results indicated that Altechromone A has anti-inflammatory activity in a CuSO₄-, tail-cutting-, and LPS-induced inflammatory model in zebrafish, respectively. In addition, Altechromone A greatly reduced the number of neutrophils, improved intestinal motility and efflux efficiency, alleviated intestinal damage, and reduced reactive oxygen species production in the TNBS-induced IBD zebrafish model. The transcriptomics sequencing and real-time qPCR indicated that Altechromone A inhibited the expression of pro-inflammatory genes including TNF-α, NF-κB, IL-1, IL-1β, IL-6, and NLRP3. Therefore, these data indicate that Altechromone A exhibits therapeutic effects in IBD by inhibiting the inflammatory response. Full article

(This article belongs to the Special Issue Zebrafish Models in Marine Drug Discovery)

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15 pages, 31783 KiB

Open AccessArticle

Exploring the Diversity and Specificity of Secondary Biosynthetic Potential in Rhodococcus

by Gang-Ao Hu, Yue Song, Shi-Yi Liu, Wen-Chao Yu, Yan-Lei Yu, Jian-Wei Chen, Hong Wang and Bin Wei

Mar. Drugs 2024, 22(9), 409; https://doi.org/10.3390/md22090409 - 6 Sep 2024

Abstract

The actinomycete genus Rhodococcus is known for its diverse biosynthetic enzymes, with potential in pollutant degradation, chemical biocatalysis, and natural product exploration. Comparative genomics have analyzed the distribution patterns of non-ribosomal peptide synthetases (NRPSs) in Rhodococcus. The diversity and specificity of its [...] Read more.

The actinomycete genus Rhodococcus is known for its diverse biosynthetic enzymes, with potential in pollutant degradation, chemical biocatalysis, and natural product exploration. Comparative genomics have analyzed the distribution patterns of non-ribosomal peptide synthetases (NRPSs) in Rhodococcus. The diversity and specificity of its secondary metabolism offer valuable insights for exploring natural products, yet remain understudied. In the present study, we analyzed the distribution patterns of biosynthetic gene clusters (BGCs) in the most comprehensive Rhodococcus genome data to date. The results show that 86.5% of the gene cluster families (GCFs) are only distributed in a specific phylogenomic-clade of Rhodococcus, with the most predominant types of gene clusters being NRPS and ribosomally synthesized and post-translationally modified peptides (RiPPs). In-depth mining of RiPP gene clusters revealed that Rhodococcus encodes many clade-specific novel RiPPs, with thirteen core peptides showing antibacterial potential. High-throughput elicitor screening (HiTES) and non-targeted metabolomics revealed that a marine-derived Rhodococcus strain produces a large number of new aurachin-like compounds when exposed to specific elicitors. The present study highlights the diversity and specificity of secondary biosynthetic potential in Rhodococcus, and provides valuable information for the targeted exploration of novel natural products from Rhodococcus, especially for phylogenomic-clade-specific metabolites. Full article

(This article belongs to the Special Issue Discovery of Marine Natural Products in China: Selected Papers from the 16th National Annual Conference and 2023 International Symposium on Marine Drugs (16-NASMD) Conference)

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17 pages, 2715 KiB

Open AccessArticle

Sphaerococcenol A Derivatives: Design, Synthesis, and Cytotoxicity

by Dídia Sousa, Milene A. G. Fortunato, Joana Silva, Mónica Pingo, Alice Martins, Carlos A. M. Afonso, Rui Pedrosa, Filipa Siopa and Celso Alves

Mar. Drugs 2024, 22(9), 408; https://doi.org/10.3390/md22090408 - 5 Sep 2024

Abstract

Sphaerococcenol A is a cytotoxic bromoditerpene biosynthesized by the red alga Sphaerococcus coronopifolius. A series of its analogues (1–6) was designed and semi-synthesized using thiol-Michael additions and enone reduction, and the structures of these analogues were characterized by [...] Read more.

Sphaerococcenol A is a cytotoxic bromoditerpene biosynthesized by the red alga Sphaerococcus coronopifolius. A series of its analogues (1–6) was designed and semi-synthesized using thiol-Michael additions and enone reduction, and the structures of these analogues were characterized by spectroscopic methods. Cytotoxic analyses (1–100 µM; 24 h) were accomplished on A549, DU-145, and MCF-7 cells. The six novel sphaerococcenol A analogues displayed an IC₅₀ range between 14.31 and 70.11 µM on A549, DU-145, and MCF-7 malignant cells. Compound 1, resulting from the chemical addition of 4-methoxybenzenethiol, exhibited the smallest IC₅₀ values on the A549 (18.70 µM) and DU-145 (15.82 µM) cell lines, and compound 3, resulting from the chemical addition of propanethiol, exhibited the smallest IC₅₀ value (14.31 µM) on MCF-7 cells. The highest IC₅₀ values were exhibited by compound 4, suggesting that the chemical addition of benzylthiol led to a loss of cytotoxic activity. The remaining chemical modifications were not able to potentiate the cytotoxicity of the original compounds. Regarding A549 cell viability, analogue 1 exhibited a marked effect on mitochondrial function, which was accompanied by an increase in ROS levels, Caspase-3 activation, and DNA fragmentation and condensation. This study opens new avenues for research by exploring sphaerococcenol A as a scaffold for the synthesis of novel bioactive molecules. Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents 3.0)

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16 pages, 4560 KiB

Open AccessArticle

The Cytochalasins and Polyketides from a Mangrove Endophytic Fungus Xylaria arbuscula QYF

by Qi Tan, Xinyu Ye, Siqi Fu, Yihao Yin, Yufeng Liu, Jianying Wu, Fei Cao, Bo Wang, Tingshun Zhu, Wencong Yang and Zhigang She

Mar. Drugs 2024, 22(9), 407; https://doi.org/10.3390/md22090407 - 5 Sep 2024

Abstract

Twelve compounds, including four undescribed cytochalasins, xylariachalasins A–D (1–4), four undescribed polyketides (5–8), and four known cytochalasins (9–12), were isolated from the mangrove endophytic fungus Xylaria arbuscula QYF. Their structures and [...] Read more.

Twelve compounds, including four undescribed cytochalasins, xylariachalasins A–D (1–4), four undescribed polyketides (5–8), and four known cytochalasins (9–12), were isolated from the mangrove endophytic fungus Xylaria arbuscula QYF. Their structures and absolute configurations were established by extensive spectroscopic analyses (1D and 2D NMR, HRESIMS), electronic circular dichroism (ECD) calculations, ¹³C NMR calculation and DP4+ analysis, single-crystal X-ray diffraction, and the modified Mosher ester method. Compounds 1 and 2 are rare cytochalasin hydroperoxides. In bioactivity assays, Compound 2 exhibited moderate antimicrobial activities against Staphylococcus aureus and Candida albicans with MIC values of 12.5 μM for both Compound 10 exhibited significant cytotoxic activity against MDA-MB-435 with an IC₅₀ value of 3.61 ± 1.60 μM. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products, 2nd Edition)

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26 pages, 1747 KiB

Open AccessArticle

Stress-Induced Production of Bioactive Oxylipins in Marine Microalgae

by Amandyne Linares-Maurizi, Rana Awad, Anaelle Durbec, Guillaume Reversat, Valérie Gros, Jean-Marie Galano, Justine Bertrand-Michel, Thierry Durand, Rémi Pradelles, Camille Oger and Claire Vigor

Mar. Drugs 2024, 22(9), 406; https://doi.org/10.3390/md22090406 - 4 Sep 2024

Abstract

Microalgae, stemming from a complex evolutionary lineage, possess a metabolic composition influenced by their evolutionary journey. They have the capacity to generate diverse polyunsaturated fatty acids (PUFAs), akin to those found in terrestrial plants and oily fish. Also, because of their numerous double [...] Read more.

Microalgae, stemming from a complex evolutionary lineage, possess a metabolic composition influenced by their evolutionary journey. They have the capacity to generate diverse polyunsaturated fatty acids (PUFAs), akin to those found in terrestrial plants and oily fish. Also, because of their numerous double bonds, these metabolic compounds are prone to oxidation processes, leading to the creation of valuable bioactive molecules called oxylipins. Moreover, owing to their adaptability across various environments, microalgae offer an intriguing avenue for biosynthesizing these compounds. Thus, modifying the culture conditions could potentially impact the profiles of oxylipins. Indeed, the accumulation of oxylipins in microalgae is subject to the influence of growth conditions, nutrient availability, and stressors, and adjusting these factors can enhance their production in microalgae culture. Consequently, the present study scrutinized the LC-MS/MS profiles of oxylipins from three marine microalgae species (two Haptagophytes and one Chlorophyte) cultivated in 1 L of photobioreactors under varying stress-inducing conditions, such as the introduction of H₂O₂, EtOAc, and NaCl, during their exponential growth phase. Approximately 50 oxylipins were identified, exhibiting different concentrations depending on the species and growth circumstances. This research suggests that microalgae metabolisms can be steered toward the production of bioactive oxylipins through modifications in the culture conditions. In this instance, the application of a low dose of hydrogen peroxide to Mi 124 appears to stimulate the production of nonenzymatic oxylipins. For Mi136, it is the application of salt stress that seems to increase the overall production of oxylipins. In the case of Mi 168, either a low concentration of H₂O₂ or a high concentration of AcOEt appears to have this effect. Full article

(This article belongs to the Special Issue Lipidomics in Marine Microalgae and Seaweeds: Applications and Perspectives)

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35 pages, 1776 KiB

Open AccessReview

Marine Microorganism Molecules as Potential Anti-Inflammatory Therapeutics

by Malia Lasalo, Thierry Jauffrais, Philippe Georgel and Mariko Matsui

Mar. Drugs 2024, 22(9), 405; https://doi.org/10.3390/md22090405 - 3 Sep 2024

Abstract

The marine environment represents a formidable source of biodiversity, is still largely unexplored, and has high pharmacological potential. Indeed, several bioactive marine natural products (MNPs), including immunomodulators, have been identified in the past decades. Here, we review how this reservoir of bioactive molecules [...] Read more.

The marine environment represents a formidable source of biodiversity, is still largely unexplored, and has high pharmacological potential. Indeed, several bioactive marine natural products (MNPs), including immunomodulators, have been identified in the past decades. Here, we review how this reservoir of bioactive molecules could be mobilized to develop novel anti-inflammatory compounds specially produced by or derived from marine microorganisms. After a detailed description of the MNPs exerting immunomodulatory potential and their biological target, we will briefly discuss the challenges associated with discovering anti-inflammatory compounds from marine microorganisms. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)

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16 pages, 3145 KiB

Open AccessArticle

Light Spectra, a Promising Tool to Modulate Ulva lacinulata Productivity and Composition

by Helena M. Amaro, Fernando Pagels, Rosa Melo, Antoine Fort, Ronan Sulpice, Graciliana Lopes, Isabel Costa and Isabel Sousa-Pinto

Mar. Drugs 2024, 22(9), 404; https://doi.org/10.3390/md22090404 - 3 Sep 2024

Abstract

Light quality is a key factor affecting algal growth and biomass composition, particularly pigments such as carotenoids, known for their antioxidant properties. Light-emitting diodes (LEDs) are becoming a cost-effective solution for indoor seaweed production when compared to fluorescent bulbs, allowing full control of [...] Read more.

Light quality is a key factor affecting algal growth and biomass composition, particularly pigments such as carotenoids, known for their antioxidant properties. Light-emitting diodes (LEDs) are becoming a cost-effective solution for indoor seaweed production when compared to fluorescent bulbs, allowing full control of the light spectra. However, knowledge of its effects on Ulva biomass production is still scarce. In this study, we investigated the effects of LEDs on the phenotype of an Ulva lacinulata strain, collected on the Northern Portuguese coast. Effects of white (W), green (G), red (R), and blue (B) LEDs were evaluated for growth (fresh weight and area), photosynthetic activity, sporulation, and content of pigments and antioxidant compounds. The results showed that there were no significant differences in terms of fresh weight accumulation and reduced sporulation among the tested LEDs, while W light induced the highest expansion rate. Under G, U. lacinulata attained a quicker photoacclimation, and the highest content of pigments and total antioxidant activity; but with R and W, antioxidant compounds against the specific radicals O₂^•− and ^•NO were produced in a higher content when compared to other LEDs. Altogether, this study demonstrated that it is possible to modulate the bioactive properties of U. lacinulata by using W, R, and G light, opening the path to the production of biomass tailored for specific nutraceutical applications. Full article

(This article belongs to the Special Issue Biotechnology of Algae)

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11 pages, 2819 KiB

Open AccessArticle

New Sesquiterpenoids from the Mangrove-Derived Fungus Talaromyces sp. as Modulators of Nuclear Receptors

by Tanwei Gu, Jian Cai, Danni Xie, Jianglian She, Yonghong Liu, Xuefeng Zhou and Lan Tang

Mar. Drugs 2024, 22(9), 403; https://doi.org/10.3390/md22090403 - 3 Sep 2024

Abstract

Four new sesquiterpenoids, talaroterpenes A–D (1–4), were isolated from the mangrove-derived fungus Talaromyces sp. SCSIO 41412. The structures of compounds 1–4 were elucidated through comprehensive NMR and MS spectroscopic analyses. The absolute configurations of 1–4 [...] Read more.

Four new sesquiterpenoids, talaroterpenes A–D (1–4), were isolated from the mangrove-derived fungus Talaromyces sp. SCSIO 41412. The structures of compounds 1–4 were elucidated through comprehensive NMR and MS spectroscopic analyses. The absolute configurations of 1–4 were assigned based on single-crystal X-ray diffraction and calculated electronic circular dichroism analysis. Talaroterpenes A–D (1–4) were evaluated with their regulatory activities on nuclear receptors in HepG2 cells. Under the concentrations of 200 μM, 1, 3 and 4 exhibited varying degrees of activation on ABCA1 and PPARα, while 4 showed the strongest activities. Furthermore, 4 induced significant alterations in the expression of downstream target genes CLOCK and BMAL1 of RORα, and the in silico molecular docking analysis supported the direct binding interactions of 4 with RORα protein. This study revealed that talaroterpene D (4) was a new potential non-toxic modulator of nuclear receptors. Full article

(This article belongs to the Special Issue Marine Bioactive Compound Discovery by Combining Virtual with Actual Laboratory Experiments)

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48 pages, 5981 KiB

Open AccessReview

An Overview of Secondary Metabolites from Soft Corals of the Genus Capnella over the Five Decades: Chemical Structures, Pharmacological Activities, NMR Data, and Chemical Synthesis

by Can-Qi Liu, Qi-Bin Yang, Ling Zhang and Lin-Fu Liang

Mar. Drugs 2024, 22(9), 402; https://doi.org/10.3390/md22090402 - 2 Sep 2024

Abstract

There has been no specific review on the secondary metabolites from soft corals of the genus Capnella till now. In this work, all secondary metabolites from different species of the title genus were described. It covered the first work from 1974 to May [...] Read more.

There has been no specific review on the secondary metabolites from soft corals of the genus Capnella till now. In this work, all secondary metabolites from different species of the title genus were described. It covered the first work from 1974 to May 2024, spanning five decades. In the viewpoint of the general structural features, these chemical constituents were classified into four groups: sesquiterpenes, diterpenes, steroids, and lipids. Additionally, the ¹H and ¹³C NMR data of these metabolites were provided when available in the literature. Among them, sesquiterpenes were the most abundant chemical compositions from soft corals of the genus Capnella. A variety of pharmacological activities of these compounds were evaluated, such as cytotoxic, antibacterial, antifungal, and anti-inflammatory activities. In addition, the chemical synthesis works of several representative sesquiterpenes were provided. This review aims to provide an up-to-date knowledge of the chemical structures, pharmacological activities, and chemical synthesis of the chemical constituents from soft corals of the genus Capnella. Full article

(This article belongs to the Special Issue Bioactive Compounds from Soft Corals and Their Derived Microorganisms)

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