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Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules

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A special issue of Marine Drugs (ISSN 1660-3397). This special issue belongs to the section "Marine Biotechnology Related to Drug Discovery or Production".

Deadline for manuscript submissions: closed (31 March 2025) | Viewed by 24189

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Dr. Nedeljka Rosic

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1. School of Health and Human Sciences, Southern Cross University, Gold Coast, QLD 4225, Australia
2. Marine Ecology Research Centre, Southern Cross University, Military Rd., East Lismore, NSW 2480, Australia
Interests: marine biology; sequencing; molecular biology; biomedical products; gene expression; genomics; molecular genetics; epigenetics
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Dear Colleagues,

The marine environment provides a rich source of bioactive compounds which could be efficiently applied in various industries, benefiting the shift towards environmentally sustainable green sectors, environmental protection, and the balanced use of natural resources. Proteomic studies assess all proteins produced in organisms, differential gene expression, and its impact on proteomics profiles, as well as proteins’ activity, stability, degradation, modification, interactions, and their effect on metabolic pathways. Wide-ranging aspects of proteomics research are emerging, including modern technologies implementing artificial intelligence (AI)-based methods. The extension of knowledge regarding proteomics facilitates a better understanding of the bioactive capacities of bioproducts found in aquatic species and is especially important in the field of medical research, which urgently requires new and improved drug therapies.

We would like to invite scientists to submit their high-quality studies, including novel research and review articles addressing proteomics research, to this Special Issue of Marine Drugs in relation to the following topics:

Protein expression profiling and the influence of differential gene expression;
Proteome mining for the identification of biological target molecules;
Post-translational modification of proteins and impact on the function;
Functional proteomics, including protein production, degradation, and/or stability;
Structural proteomics and protein–protein interactions.

Dr. Nedeljka Rosic
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

proteomics
bioproducts
anti-bacterial
anti-tumour
anti-viral
anti-aging
anti-inflammatory
anti-fungal

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Related Special Issue

Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules, 2nd Edition in Marine Drugs (1 article)

Published Papers (10 papers)

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Research

Jump to: Review

17 pages, 2945 KiB

Open AccessArticle

Fingerprint Analysis and Comparison of Activity Differences of Crude Venom from Five Species of Vermivorous Cone Snail in the South China Sea

by Shibo Sun, Yanling Liao, Jinxing Fu, Yanxia Liang, Yurong Chen, Kailin Mao and Bingmiao Gao

Mar. Drugs 2025, 23(3), 102; https://doi.org/10.3390/md23030102 - 25 Feb 2025

Viewed by 572

Abstract

The South China Sea is rich in cone snail resources, known for producing conotoxins with diverse biological activities such as analgesic, anticancer, and insecticidal effects. In this study, five vermivorous cone snail samples were collected from the South China Sea and their crude venom was extracted to investigate the variations in venom components and activities, aiming to identify highly active samples for further research. Cluster analysis using reverse-phase high-performance liquid chromatography (RP-HPLC) fingerprints and mitochondrial cytochrome c oxidase I (COI) gene sequences revealed that the diversity of venom components across different conotoxin species is genetically correlated. Activity assays demonstrated that all five cone snail venoms exhibited lethal effects on insects and zebrafish. Notably, the crude venom of Conus quercinus showed the highest insecticidal activity with an LD₅₀ of 0.6 μg/mg, while C. tessellatus venom exhibited the most potent zebrafish lethality with an LD₅₀ of 0.2 μg/mg. Furthermore, the crude venom from four cone snail species demonstrated toxicity against ovarian cancer cells, and only C. caracteristicu venom displayed significant analgesic activity. This study systematically identifies cone snail samples with promising insecticidal, anticancer, and analgesic properties, paving the way for the development and utilization of cone snail resources from the South China Sea and offering a novel approach for advancing marine peptide drug research. Full article

(This article belongs to the Special Issue Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules)

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25 pages, 4725 KiB

Open AccessArticle

Bioprospecting Bioactive Peptides in Halobatrachus didactylus Body Mucus: From In Silico Insights to Essential In Vitro Validation

by Marta Fernandez Cunha, Ezequiel R. Coscueta, María Emilia Brassesco, Frederico Almada, David Gonçalves and Maria Manuela Pintado

Mar. Drugs 2025, 23(2), 82; https://doi.org/10.3390/md23020082 - 13 Feb 2025

Viewed by 786

Abstract

Fish body mucus plays a protective role, especially in Halobatrachus didactylus, which inhabits intertidal zones vulnerable to anthropogenic contaminants. In silico predicted bioactive peptides were identified in its body mucus, namely, EDNSELGQETPTLR (HdKTLR), DPPNPKNL (HdKNL), PAPPPPPP (HdPPP), VYPFPGPLPN (HdVLPN), and PFPGPLPN (HdLPN). These peptides were studied in vitro for bioactivities and aggregation behavior under different ionic strengths and pH values. Size exclusion chromatography revealed significant peptide aggregation at 344 mM and 700 mM ionic strengths at pH 7.0, decreasing at pH 3.0 and pH 5.0. Although none exhibited antimicrobial properties, they inhibited Pseudomonas aeruginosa biofilm formation. Notably, HdVLPN demonstrated potential antioxidant activity (ORAC: 1.560 μmol TE/μmol of peptide; ABTS: 1.755 μmol TE/μmol of peptide) as well as HdLPN (ORAC: 0.195 μmol TE/μmol of peptide; ABTS: 0.128 μmol TE/μmol of peptide). Antioxidant activity decreased at pH 5.0 and pH 3.0. Interactions between the peptides and mucus synergistically enhanced antioxidant effects. HdVLPN and HdLPN were non-toxic to Caco-2 and HaCaT cells at 100 μg of peptide/mL. HdPPP showed potential antihypertensive and antidiabetic effects, with IC₅₀ values of 557 μg of peptide/mL for ACE inhibition and 1700 μg of peptide/mL for α-glucosidase inhibition. This study highlights the importance of validating peptide bioactivities in vitro, considering their native environment (mucus), and bioprospecting novel bioactive molecules while promoting species conservation. Full article

(This article belongs to the Special Issue Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules)

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27 pages, 8426 KiB

Open AccessArticle

Revealing the Diversity of Sequences, Structures, and Targets of Peptides from South China Sea Macrodactyla doreensis Based on Transcriptomics

by Ziqiang Hua, Yanling Liao, Jinxing Fu, Xinru Li, Qianxia Xu, Limin Lin, Meiling Huang and Bingmiao Gao

Mar. Drugs 2024, 22(10), 470; https://doi.org/10.3390/md22100470 - 12 Oct 2024

Cited by 2 | Viewed by 1577

Abstract

The South China Sea is rich in sea anemone resources, and the protein and peptide components from sea anemone toxins comprise an important treasure trove for researchers to search for leading compounds. This study conducted a comprehensive transcriptomic analysis of the tentacles and column of Macrodactyla doreensis and explored the distribution and diversity of proteins and peptides in depth using bioinformatics, initially constructing a putative protein and peptide database. In this database, typical peptide families are identified through amino acid sequence analysis, and their 3D structures and potential biological activities are revealed through AlphaFold2 modeling and molecular docking. A total of 4239 transcripts were identified, of which the putative protein accounted for 81.53%. The highest content comprised immunoglobulin and a variety of proteases, mainly distributed in the column and related to biological functions. Importantly, the putative peptide accounted for 18.47%, containing ShK domain and Kunitz-type peptides, mainly distributed in the tentacles and related to offensive predatory behavior. Interestingly, 40 putative peptides belonging to eight typical peptide families were identified, and their structures and targets were predicted. This study reveals the diversity and complexity of Macrodactyla doreensis toxins and predicts their structure and targets based on amino acid sequences, providing a feasible approach for research regarding the discovery of peptides with potentially high activity. Full article

(This article belongs to the Special Issue Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules)

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22 pages, 1425 KiB

Open AccessArticle

Proteomic Analysis and Biochemical Characterization of the Nematocyst Extract of the Hydrozoan Velella velella

by Eleonora Tassara, Ivan Mikšík, Petr Pompach, Gian Luigi Mariottini, Liang Xiao, Marco Giovine and Marina Pozzolini

Mar. Drugs 2024, 22(10), 468; https://doi.org/10.3390/md22100468 - 12 Oct 2024

Cited by 2 | Viewed by 1588

Abstract

The venom contained within cnidarian nematocysts has a complex composition and holds significant potential for biotechnological applications. In this context, one of the most effective methods for studying nematocyst contents is the proteomic approach, which can detect even trace amounts of compounds while minimizing the need for large-scale animal collection, thus helping to preserve ecosystem integrity. This study aimed to provide a comprehensive proteomic and biochemical characterization of the crude nematocyst extract from the common hydrozoan Velella velella. Despite not being harmful to humans, the analysis of the crude venom extract from V. velella brought to the identification of 783 different proteins, categorized into structural components, enzymes, and potential toxins, revealing a qualitative composition of the venom similar to that of other more toxic cnidarians. Biochemical assays confirmed the presence of various active hydrolytic enzymes within the extract, including proteases, phospholipases, hyaluronidases, DNases, and chitinases. These findings pave the road for future studies involving the pharmacological applications of Velella velella venom components through recombinant production and functional testing. Full article

(This article belongs to the Special Issue Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules)

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17 pages, 2908 KiB

Open AccessArticle

Exploring the Potential of Crassostrea nippona Hydrolysates as Dietary Supplements for Mitigating Dexamethasone-Induced Muscle Atrophy in C2C12 Cells

by M. J. M. S. Kurera, D. P. Nagahawatta, N. M. Liyanage, H. H. A. C. K. Jayawardhana, D. S. Dissanayake, Hyo-Geun Lee, Young-Sang Kim, Sang In Kang and You-Jin Jeon

Mar. Drugs 2024, 22(3), 113; https://doi.org/10.3390/md22030113 - 28 Feb 2024

Cited by 1 | Viewed by 3050

Abstract

Muscle atrophy is a detrimental and injurious condition that leads to reduced skeletal muscle mass and disruption of protein metabolism. Oyster (Crassostrea nippona) is a famous and commonly consumed shellfish in East Asia and has become a popular dietary choice worldwide. The current investigation evaluated the efficacy of C. nippona against muscle atrophy, which has become a severe health issue. Mammalian skeletal muscles are primarily responsible for efficient metabolism, energy consumption, and body movements. The proteins that regulate muscle hypertrophy and atrophy are involved in muscle growth. C. nippona extracts were enzymatically hydrolyzed using alcalase (AOH), flavourzyme (FOH), and protamex (POH) to evaluate their efficacy in mitigating dexamethasone-induced muscle damage in C2C12 cells in vitro. AOH exhibited notable cell proliferative abilities, promoting dose-dependent myotube formation. These results were further solidified by protein expression analysis. Western blot and gene expression analysis via RT-qPCR demonstrated that AOH downregulated MuRF-1, Atrogin, Smad 2/3, and Foxo-3a, while upregulating myogenin, MyoD, myosin heavy chain expression, and mTOR, key components of the ubiquitin–proteasome and mTOR signaling pathways. Finally, this study suggests that AOH holds promise for alleviating dexamethasone-induced muscle atrophy in C2C12 cells in vitro, offering insights for developing functional foods targeting conditions akin to sarcopenia. Full article

(This article belongs to the Special Issue Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules)

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19 pages, 7385 KiB

Open AccessArticle

Venomics Reveals the Venom Complexity of Sea Anemone Heteractis magnifica

by Ming Li, Kailin Mao, Meiling Huang, Yanling Liao, Jinxing Fu, Kun Pan, Qiong Shi and Bingmiao Gao

Mar. Drugs 2024, 22(2), 71; https://doi.org/10.3390/md22020071 - 28 Jan 2024

Cited by 7 | Viewed by 3207

Abstract

The venoms of various sea anemones are rich in diverse toxins, which usually play a dual role in capturing prey and deterring predators. However, the complex components of such venoms have not been well known yet. Here, venomics of integrating transcriptomic and proteomic technologies was applied for the first time to identify putative protein and peptide toxins from different tissues of the representative sea anemone, Heteractis magnifica. The transcriptomic analysis of H. magnifica identified 728 putative toxin sequences, including 442 and 381 from the tentacles and the column, respectively, and they were assigned to 68 gene superfamilies. The proteomic analysis confirmed 101 protein and peptide toxins in the venom, including 91 in the tentacles and 39 in the column. The integrated venomics also confirmed that some toxins such as the ShK-like peptides and defensins are co-expressed in both the tentacles and the column. Meanwhile, a homology analysis was conducted to predict the three-dimensional structures and potential activity of seven representative toxins. Altogether, this venomics study revealed the venom complexity of H. magnifica, which will help deepen our understanding of cnidarian toxins, thereby supporting the in-depth development of valuable marine drugs. Full article

(This article belongs to the Special Issue Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules)

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23 pages, 5111 KiB

Open AccessArticle

Marine Bioprospecting: Enzymes and Stress Proteins from the Sea Anemones Anthopleura dowii and Lebrunia neglecta

by Santos Ramírez-Carreto, Beatriz Miranda-Zaragoza, Nuno Simões, Ricardo González-Muñoz and Claudia Rodríguez-Almazán

Mar. Drugs 2024, 22(1), 12; https://doi.org/10.3390/md22010012 - 23 Dec 2023

Cited by 2 | Viewed by 2761

Abstract

The bioprospecting of sea anemone tissues and secretions has revealed that they are natural libraries of polypeptides with diverse biological activities that can be utilized to develop of biotechnological tools with potential medical and industrial applications. This study conducted a proteomic analysis of crude venom extracts from Anthopleura dowii Verrill, 1869, and Lebrunia neglecta Duchassaing & Michelotti, 1860. The obtained data allowed us to identify 201 polypeptides, of which 39% were present in both extracts. Among the obtained sequences, hydrolase-type enzymes, oxidoreductases, transferases, heat shock proteins, adhesion proteins, and protease inhibitors, among others, were identified. Interaction analysis and functional annotation indicated that these proteins are primarily involved in endoplasmic reticulum metabolic processes such as carbon metabolism and protein processing. In addition, several proteins related to oxidative stress were identified, including superoxide dismutase, peroxiredoxins, thioredoxin, and glutathione oxidase. Our results provide novel information on the polypeptide composition of the crude venom extract from sea anemones, which can be utilized to develop molecules for therapeutic tools and industrial applications. Full article

(This article belongs to the Special Issue Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules)

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17 pages, 3731 KiB

Open AccessArticle

Proteomic Identification of Plasma Components in Tachypleus tridentatus and Their Effects on the Longitudinal Bone Growth Rate in Rats

by Shu Jiang, Xinjian Qu, Siping Liu, Jun Wei, Xiangxi Yi, Yonghong Liu and Chenghai Gao

Mar. Drugs 2023, 21(2), 111; https://doi.org/10.3390/md21020111 - 3 Feb 2023

Cited by 2 | Viewed by 2290

Abstract

Tachypleus tridentatus (T. tridentatus) is a marine animal and traditional Chinese medicine. T. tridentatus plasma is a valuable resource for important medical and health-based functions. In this experiment, in order to evaluate the effect and mechanism of T. tridentatus plasma with respect to the promotion of bone tissue growth in rats, the processes of ultrafiltration and mass spectrometry were first used to separate and identify the components of T. tridentatus plasma. Then, a comparison of the effects of the T. tridentatus plasma samples, which each possessed different molecular weights, regarding the growth of the long bones of rats was conducted. Finally, transcriptomics, proteomics, and bioinformatics were all used to analyze the biological functions and related signaling pathways of the T. tridentatus plasma in order to promote rat bone growth. The results showed that the contents of amino acid residues in peptides are related to the growth promotion that was contained in the 10–30 kDa plasma group. Moreover, the T. tridentatus plasma samples were found to be higher in this respect than those in the whole plasma group. In addition, the 10–30 kDa plasma group could significantly promote bone growth activity in rats. The proteomic analysis showed that the proteins that were differentially expressed in the 10–30 kDa plasma group were mainly enriched in the PI3K-AKT signal pathway. Our study suggested that the T. tridentatus plasma possesses promising potential for the purposes of clinical use, whereby it can serve the role of a growth-promoting agent. Full article

(This article belongs to the Special Issue Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules)

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Review

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22 pages, 3728 KiB

Open AccessReview

Unveiling the Anti-Aging Potential of Marine Natural Bioproducts

by Nedeljka Rosic

Mar. Drugs 2025, 23(4), 165; https://doi.org/10.3390/md23040165 - 11 Apr 2025

Viewed by 661

Abstract

Aging is a natural process resulting in the progressive impairment of multiple functions in the human body, leading to a decline in cellular functionality and the development of aging-related diseases. External stress factors, such as ultraviolet (UV) radiation, pollution, and toxin exposure, increase oxidative stress, damage cellular repair mechanisms, and speed up aging processes. With the rise in the world’s aging population, there are enlarged demands for the use of sustainable natural products in food, nutrient supplements and cosmetics that can slow down aging and prolong healthy life and longevity. Algae, including both macroalgae and microalgae, have been recognised as a source of valuable proteins, amino acids, fatty acids, vitamins, and minerals useful for human consumption and medical applications. With increasing demands for nutraceutical and pharmaceutical bioproducts from environmentally friendly resources, the biotechnological industry, over recent decades, has had to provide new, advanced solutions using modern high-throughput omics technologies. The application of proteomics in the area of discoveries of natural products with anti-aging properties has become more popular for wide industry applications. New proteomics profiling provides a better understanding of changes occurring in protein and peptide content, their structure, function and interactions, as well as the regulatory processes and molecular pathways. Mass spectrometry-based proteomics has been used for a wide range of applications including protein identification, characterisation, as well as quantification of proteins within the proteome and sub-proteome. The application of chemical proteomics facilitated the identification of natural products approach and included the synthesis of probes and target fishing, allowing the advanced identification of proteins of interest. This review focuses on marine macro- and microalgal anti-aging compounds and novel proteomics approaches, providing recent experimental evidence of their involvement in anti-aging processes that should facilitate their use in innovative approaches and sustainable biotechnological applications. Full article

(This article belongs to the Special Issue Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules)

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20 pages, 5632 KiB

Open AccessEditor’s ChoiceReview

Biotechnological Potential of Macroalgae during Seasonal Blooms for Sustainable Production of UV-Absorbing Compounds

by Nedeljka Rosic and Carol Thornber

Mar. Drugs 2023, 21(12), 633; https://doi.org/10.3390/md21120633 - 8 Dec 2023

Cited by 3 | Viewed by 5556

Abstract

Marine macroalgae (seaweeds) are important primary global producers, with a wide distribution in oceans around the world from polar to tropical regions. Most of these species are exposed to variable environmental conditions, such as abiotic (e.g., light irradiance, temperature variations, nutrient availability, salinity levels) and biotic factors (e.g., grazing and pathogen exposure). As a result, macroalgae developed numerous important strategies to increase their adaptability, including synthesizing secondary metabolites, which have promising biotechnological applications, such as UV-absorbing Mycosporine-Like Amino Acid (MAAs). MAAs are small, water-soluble, UV-absorbing compounds that are commonly found in many marine organisms and are characterized by promising antioxidative, anti-inflammatory and photoprotective properties. However, the widespread use of MAAs by humans is often restricted by their limited bioavailability, limited success in heterologous expression systems, and low quantities recovered from the natural environment. In contrast, bloom-forming macroalgal species from all three major macroalgal clades (Chlorophyta, Phaeophyceae, and Rhodophyta) occasionally form algal blooms, resulting in a rapid increase in algal abundance and high biomass production. This review focuses on the bloom-forming species capable of producing pharmacologically important compounds, including MAAs, and the application of proteomics in facilitating macroalgal use in overcoming current environmental and biotechnological challenges. Full article

(This article belongs to the Special Issue Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules)

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