Marine Drugs

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26 pages, 5569 KiB

Open AccessFeature PaperArticle

Identification, Purification and Molecular Characterization of Chondrosin, a New Protein with Anti-tumoral Activity from the Marine Sponge Chondrosia Reniformis Nardo 1847

by Sonia Scarfì, Marina Pozzolini, Caterina Oliveri, Serena Mirata, Annalisa Salis, Gianluca Damonte, Daniela Fenoglio, Tiziana Altosole, Micha Ilan, Marco Bertolino and Marco Giovine

Mar. Drugs 2020, 18(8), 409; https://doi.org/10.3390/md18080409 - 2 Aug 2020

Cited by 11 | Viewed by 3734

Abstract

Chondrosia reniformis is a common marine demosponge showing many peculiarities, lacking silica spicules and with a body entirely formed by a dense collagenous matrix. In this paper, we have described the identification of a new cytotoxic protein (chondrosin) with selective activity against specific [...] Read more.

Chondrosia reniformis is a common marine demosponge showing many peculiarities, lacking silica spicules and with a body entirely formed by a dense collagenous matrix. In this paper, we have described the identification of a new cytotoxic protein (chondrosin) with selective activity against specific tumor cell lines, from C. reniformis, collected from the Liguria Sea. Chondrosin was extracted and purified using a salting out approach and molecular weight size exclusion chromatography. The cytotoxic fractions were then characterized by two-dimensional gel electrophoresis and mass spectrometry analysis and matched the results with C. reniformis transcriptome database. The procedure allowed for identifying a full-length cDNA encoding for a 199-amino acids (aa) polypeptide, with a signal peptide of 21 amino acids. The mature protein has a theoretical molecular weight of 19611.12 and an IP of 5.11. Cell toxicity assays showed a selective action against some tumor cell lines (RAW 264.7 murine leukemia cells in particular). Cell death was determined by extracellular calcium intake, followed by cytoplasmic reactive oxygen species overproduction. The in silico modelling of chondrosin showed a high structural homology with the N-terminal region of the ryanodine receptor/channel and a short identity with defensin. The results are discussed suggesting a possible specific interaction of chondrosin with the Cav 1.3 ion voltage calcium channel expressed on the target cell membranes. Full article

(This article belongs to the Special Issue Marine-Derived Products for Biomedicine)

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15 pages, 3785 KiB

Open AccessArticle

The Protective Effect of Echinochrome A on Extracellular Matrix of Vocal Folds in Ovariectomized Rats

by Ji Min Kim, Jeong Hun Kim, Sung-Chan Shin, Gi Cheol Park, Hyung Sik Kim, Keunyoung Kim, Hyoung Kyu Kim, Jin Han, Natalia P. Mishchenko, Elena A. Vasileva, Sergey A. Fedoreyev, Valentin A. Stonik and Byung-Joo Lee

Mar. Drugs 2020, 18(2), 77; https://doi.org/10.3390/md18020077 - 24 Jan 2020

Cited by 6 | Viewed by 2899

Abstract

Here, we investigated the effects of sex hormones on extracellular matrix (ECM)-related gene expression in the vocal fold lamina propria of ovariectomized (after ovary removal) rats and verified whether echinochrome A (ECH) exerts any therapeutic effects on ECM reconstitution after estrogen deficiency in [...] Read more.

Here, we investigated the effects of sex hormones on extracellular matrix (ECM)-related gene expression in the vocal fold lamina propria of ovariectomized (after ovary removal) rats and verified whether echinochrome A (ECH) exerts any therapeutic effects on ECM reconstitution after estrogen deficiency in ovariectomized rats. Sprague–Dawley female rats (9 weeks old) were acclimatized for a week and randomly divided into three groups (n = 15 each group) as follows: group I (sham-operated rats, SHAM), group II (ovariectomized rats, OVX), group III (ovariectomized rats treated with ECH, OVX + ECH). Rats from the OVX + ECH group were intraperitoneally injected with ECH at 10 mg/kg thrice a week after surgery for 6 weeks. And rats were sacrificed 6 weeks after ovariectomy. Estradiol levels decreased in OVX group compared with the SHAM group. ECH treatment had no effect on the levels of estradiol and expression of estrogen receptor β (ERβ). The evaluation of ECM components showed no significant changes in elastin and hyaluronic acid levels between the different groups. Collagen I and III levels were lower in OVX group than in SHAM group but increased in OVX + ECH group. The mRNA levels of matrix metalloproteinase (MMP)-1, -2, -8, and -9 were significantly higher in the OVX group than in the SHAM group, but decreased in the OVX + ECH group. Thus, changes were observed in ECM-related genes in the OVX group upon estradiol deficiency that were ameliorated by ECH administration. Thus, the vocal fold is an estradiol-sensitive target organ and ECH may have protective effects on the ECM of vocal folds in ovariectomized rats. Full article

(This article belongs to the Special Issue Marine-Derived Products for Biomedicine)

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14 pages, 1671 KiB

Open AccessArticle

Novel Efficient Bioprocessing of Marine Chitins into Active Anticancer Prodigiosin

by Van Bon Nguyen, Shan-Ping Chen, Thi Hanh Nguyen, Minh Trung Nguyen, Thi Thanh Thao Tran, Chien Thang Doan, Thi Ngoc Tran, Anh Dzung Nguyen, Yao-Haur Kuo and San-Lang Wang

Mar. Drugs 2020, 18(1), 15; https://doi.org/10.3390/md18010015 - 23 Dec 2019

Cited by 33 | Viewed by 5470

Abstract

Marine chitins (MC) have been utilized for the production of vast array of bioactive products, including chitooligomers, chitinase, chitosanase, antioxidants, anti-NO, and antidiabetic compounds. The aim of this study is the bioprocessing of MC into a potent anticancer compound, prodigiosin (PG), via microbial [...] Read more.

Marine chitins (MC) have been utilized for the production of vast array of bioactive products, including chitooligomers, chitinase, chitosanase, antioxidants, anti-NO, and antidiabetic compounds. The aim of this study is the bioprocessing of MC into a potent anticancer compound, prodigiosin (PG), via microbial fermentation. This bioactive compound was produced by Serratia marcescens TKU011 with the highest yield of 4.62 mg/mL at the optimal conditions of liquid medium with initial pH of 5.65–6.15 containing 1% α-chitin, 0.6% casein, 0.05% K₂HPO₄, and 0.1% CaSO₄. Fermentation was kept at 25 °C for 2 d. Notably, α-chitin was newly investigated as the major potential material for PG production via fermentation; the salt CaSO₄ was also found to play the key role in the enhancement of PG yield of Serratia marcescens fermentation for the first time. PG was qualified and identified based on specific UV, MALDI-TOF MS analysis. In the biological activity tests, purified PG demonstrated potent anticancer activities against A549, Hep G2, MCF-7, and WiDr with the IC₅₀ values of 0.06, 0.04, 0.04, and 0.2 µg/mL, respectively. Mytomycin C, a commercial anti-cancer compound was also tested for comparison purpose, showing weaker activity with the IC₅₀ values of 0.11, 0.1, 0.14, and 0.15 µg/mL, respectively. As such, purified PG displayed higher 2.75-fold, 1.67-fold, and 3.25-fold efficacy than Mytomycin C against MCF-7, A549, and Hep G2, respectively. The results suggest that marine chitins are valuable sources for production of prodigiosin, a potential candidate for cancer drugs. Full article

(This article belongs to the Special Issue Marine-Derived Products for Biomedicine)

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13 pages, 3294 KiB

Open AccessArticle

Neurotrophic Effect of Fish-Lecithin Based Nanoliposomes on Cortical Neurons

by Catherine Malaplate, Aurelia Poerio, Marion Huguet, Claire Soligot, Elodie Passeri, Cyril J. F. Kahn, Michel Linder, Elmira Arab-Tehrany and Frances T. Yen

Mar. Drugs 2019, 17(7), 406; https://doi.org/10.3390/md17070406 - 9 Jul 2019

Cited by 15 | Viewed by 3833

Abstract

Lipids play multiple roles in preserving neuronal function and synaptic plasticity, and polyunsaturated fatty acids (PUFAs) have been of particular interest in optimizing synaptic membrane organization and function. We developed a green-based methodology to prepare nanoliposomes (NL) from lecithin that was extracted from [...] Read more.

Lipids play multiple roles in preserving neuronal function and synaptic plasticity, and polyunsaturated fatty acids (PUFAs) have been of particular interest in optimizing synaptic membrane organization and function. We developed a green-based methodology to prepare nanoliposomes (NL) from lecithin that was extracted from fish head by-products. These NL range between 100–120 nm in diameter, with an n-3/n-6 fatty acid ratio of 8.88. The high content of n-3 PUFA (46.3% of total fatty acid content) and docosahexanoic acid (26%) in these NL represented a means for enrichment of neuronal membranes that are potentially beneficial for neuronal growth and synaptogenesis. To test this, the primary cultures of rat embryo cortical neurons were incubated with NL on day 3 post-culture for 24 h, followed by immunoblots or immunofluorescence to evaluate the NL effects on synaptogenesis, axonal growth, and dendrite formation. The results revealed that NL-treated cells displayed a level of neurite outgrowth and arborization on day 4 that was similar to those of untreated cells on day 5 and 6, suggesting accelerated synapse formation and neuronal development in the presence of NL. We propose that fish-derived NL, by virtue of their n-3 PUFA profile and neurotrophic effects, represent a new innovative bioactive vector for developing preventive or curative treatments for neurodegenerative diseases. Full article

(This article belongs to the Special Issue Marine-Derived Products for Biomedicine)

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19 pages, 4350 KiB

Open AccessArticle

Fucoidan-Stabilized Gold Nanoparticle-Mediated Biofilm Inhibition, Attenuation of Virulence and Motility Properties in Pseudomonas aeruginosa PAO1

by Fazlurrahman Khan, Panchanathan Manivasagan, Jang-Won Lee, Dung Thuy Nguyen Pham, Junghwan Oh and Young-Mog Kim

Mar. Drugs 2019, 17(4), 208; https://doi.org/10.3390/md17040208 - 3 Apr 2019

Cited by 79 | Viewed by 7295

Abstract

The emergence of antibiotic resistance in Pseudomonas aeruginosa due to biofilm formation has transformed this opportunistic pathogen into a life-threatening one. Biosynthesized nanoparticles are increasingly being recognized as an effective anti-biofilm strategy to counter P. aeruginosa biofilms. In the present study, gold nanoparticles [...] Read more.

The emergence of antibiotic resistance in Pseudomonas aeruginosa due to biofilm formation has transformed this opportunistic pathogen into a life-threatening one. Biosynthesized nanoparticles are increasingly being recognized as an effective anti-biofilm strategy to counter P. aeruginosa biofilms. In the present study, gold nanoparticles (AuNPs) were biologically synthesized and stabilized using fucoidan, which is an active compound sourced from brown seaweed. Biosynthesized fucoidan-stabilized AuNPs (F-AuNPs) were subjected to characterization using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), field emission transmission electron microscopy (FE-TEM), dynamic light scattering (DLS), and energy dispersive X-ray diffraction (EDX). The biosynthesized F-AuNPs were then evaluated for their inhibitory effects on P. aeruginosa bacterial growth, biofilm formation, virulence factor production, and bacterial motility. Overall, the activities of F-AuNPs towards P. aeruginosa were varied depending on their concentration. At minimum inhibitory concentration (MIC) (512 µg/mL) and at concentrations above MIC, F-AuNPs exerted antibacterial activity. In contrast, the sub-inhibitory concentration (sub-MIC) levels of F-AuNPs inhibited biofilm formation without affecting bacterial growth, and eradicated matured biofilm. The minimum biofilm inhibition concentration (MBIC) and minimum biofilm eradication concentration (MBEC) were identified as 128 µg/mL. Furthermore, sub-MICs of F-AuNPs also attenuated the production of several important virulence factors and impaired bacterial swarming, swimming, and twitching motilities. Findings from the present study provide important insights into the potential of F-AuNPs as an effective new drug for controlling P. aeruginosa-biofilm-related infections. Full article

(This article belongs to the Special Issue Marine-Derived Products for Biomedicine)

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17 pages, 6676 KiB

Open AccessArticle

New Source of 3D Chitin Scaffolds: The Red Sea Demosponge Pseudoceratina arabica (Pseudoceratinidae, Verongiida)

by Lamiaa A. Shaala, Hani Z. Asfour, Diaa T. A. Youssef, Sonia Żółtowska-Aksamitowska, Marcin Wysokowski, Mikhail Tsurkan, Roberta Galli, Heike Meissner, Iaroslav Petrenko, Konstantin Tabachnick, Viatcheslav N. Ivanenko, Nicole Bechmann, Lyubov V. Muzychka, Oleg B. Smolii, Rajko Martinović, Yvonne Joseph, Teofil Jesionowski and Hermann Ehrlich

Mar. Drugs 2019, 17(2), 92; https://doi.org/10.3390/md17020092 - 1 Feb 2019

Cited by 34 | Viewed by 5306

Abstract

The bioactive bromotyrosine-derived alkaloids and unique morphologically-defined fibrous skeleton of chitin origin have been found recently in marine demosponges of the order Verongiida. The sophisticated three-dimensional (3D) structure of skeletal chitinous scaffolds supported their use in biomedicine, tissue engineering as well as in [...] Read more.

The bioactive bromotyrosine-derived alkaloids and unique morphologically-defined fibrous skeleton of chitin origin have been found recently in marine demosponges of the order Verongiida. The sophisticated three-dimensional (3D) structure of skeletal chitinous scaffolds supported their use in biomedicine, tissue engineering as well as in diverse modern technologies. The goal of this study was the screening of new species of the order Verongiida to find another renewable source of naturally prefabricated 3D chitinous scaffolds. Special attention was paid to demosponge species, which could be farmed on large scale using marine aquaculture methods. In this study, the demosponge Pseudoceratina arabica collected in the coastal waters of the Egyptian Red Sea was examined as a potential source of chitin for the first time. Various bioanalytical tools including scanning electron microscopy (SEM), fluorescence microscopy, FTIR analysis, Calcofluor white staining, electrospray ionization mass spectrometry (ESI-MS), as well as a chitinase digestion assay were successfully used to confirm the discovery of α-chitin within the skeleton of P. arabica. The current finding should make an important contribution to the field of application of this verongiid sponge as a novel renewable source of biologically-active metabolites and chitin, which are important for development of the blue biotechnology especially in marine oriented biomedicine. Full article

(This article belongs to the Special Issue Marine-Derived Products for Biomedicine)

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18 pages, 3995 KiB

Open AccessArticle

From Aggregates to Porous Three-Dimensional Scaffolds through a Mechanochemical Approach to Design Photosensitive Chitosan Derivatives

by Kseniia N. Bardakova, Tatiana A. Akopova, Alexander V. Kurkov, Galina P. Goncharuk, Denis V. Butnaru, Vitaliy F. Burdukovskii, Artem A. Antoshin, Ivan A. Farion, Tatiana M. Zharikova, Anatoliy B. Shekhter, Vladimir I. Yusupov, Peter S. Timashev and Yury A. Rochev

Mar. Drugs 2019, 17(1), 48; https://doi.org/10.3390/md17010048 - 10 Jan 2019

Cited by 18 | Viewed by 7696

Abstract

The crustacean processing industry produces large quantities of waste by-products (up to 70%). Such wastes could be used as raw materials for producing chitosan, a polysaccharide with a unique set of biochemical properties. However, the preparation methods and the long-term stability of chitosan-based [...] Read more.

The crustacean processing industry produces large quantities of waste by-products (up to 70%). Such wastes could be used as raw materials for producing chitosan, a polysaccharide with a unique set of biochemical properties. However, the preparation methods and the long-term stability of chitosan-based products limit their application in biomedicine. In this study, different scale structures, such as aggregates, photo-crosslinked films, and 3D scaffolds based on mechanochemically-modified chitosan derivatives, were successfully formed. Dynamic light scattering revealed that aggregation of chitosan derivatives becomes more pronounced with an increase in the number of hydrophobic substituents. Although the results of the mechanical testing revealed that the plasticity of photo-crosslinked films was 5–8% higher than that for the initial chitosan films, their tensile strength remained unchanged. Different types of polymer scaffolds, such as flexible and porous ones, were developed by laser stereolithography. In vivo studies of the formed structures showed no dystrophic and necrobiotic changes, which proves their biocompatibility. Moreover, the wavelet analysis was used to show that the areas of chitosan film degradation were periodic. Comparing the results of the wavelet analysis and X-ray diffraction data, we have concluded that degradation occurs within less ordered amorphous regions in the polymer bulk. Full article

(This article belongs to the Special Issue Marine-Derived Products for Biomedicine)

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21 pages, 5103 KiB

Open AccessArticle

Trichormus variabilis (Cyanobacteria) Biomass: From the Nutraceutical Products to Novel EPS-Cell/Protein Carrier Systems

by Erika Bellini, Matteo Ciocci, Saverio Savio, Simonetta Antonaroli, Dror Seliktar, Sonia Melino and Roberta Congestri

Mar. Drugs 2018, 16(9), 298; https://doi.org/10.3390/md16090298 - 27 Aug 2018

Cited by 13 | Viewed by 5521

Abstract

A native strain of the heterocytous cyanobacterium Trichormus variabilis VRUC 168 was mass cultivated in a low-cost photobioreactor for a combined production of Polyunsaturated Fatty Acids (PUFA) and Exopolymeric Substances (EPS) from the same cyanobacterial biomass. A sequential extraction protocol was optimized leading [...] Read more.

A native strain of the heterocytous cyanobacterium Trichormus variabilis VRUC 168 was mass cultivated in a low-cost photobioreactor for a combined production of Polyunsaturated Fatty Acids (PUFA) and Exopolymeric Substances (EPS) from the same cyanobacterial biomass. A sequential extraction protocol was optimized leading to high yields of Released EPS (REPS) and PUFA, useful for nutraceutical products and biomaterials. REPS were extracted and characterized by chemical staining, Reversed Phase-High-Performance Liquid Chromatography (RP-HPLC), Fourier Transform Infrared Spectroscopy (FT-IR) and other spectroscopic techniques. Due to their gelation property, REPS were used to produce a photo-polymerizable hybrid hydrogel (REPS-Hy) with addition of polyethylene glycol diacrylated (PEGDa). REPS-Hy was stable over time and resistant to dehydration and spontaneous hydrolysis. The rheological and functional properties of REPS-Hy were studied. The enzyme carrier ability of REPS-Hy was assessed using the detoxification enzyme thiosulfate:cyanide sulfur transferase (TST), suggesting the possibility to use REPS-Hy as an enzymatic hydrogel system. Finally, REPS-Hy was used as a scaffold for culturing human mesenchymal stem cells (hMSCs). The cell seeding onto the REPS-Hy and the cell embedding into 3D-REPS-Hy demonstrated a scaffolding property of REPS-Hy with non-cytotoxic effect, suggesting potential applications of cyanobacteria REPS for producing enzyme- and cell-carrier systems. Full article

(This article belongs to the Special Issue Marine-Derived Products for Biomedicine)

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Review

Jump to: Research

59 pages, 8614 KiB

Open AccessReview

Marine Cyanobacteria and Microalgae Metabolites—A Rich Source of Potential Anticancer Drugs

by Arijit Mondal, Sankhadip Bose, Sabyasachi Banerjee, Jayanta Kumar Patra, Jai Malik, Sudip Kumar Mandal, Kaitlyn L. Kilpatrick, Gitishree Das, Rout George Kerry, Carmela Fimognari and Anupam Bishayee

Mar. Drugs 2020, 18(9), 476; https://doi.org/10.3390/md18090476 - 19 Sep 2020

Cited by 66 | Viewed by 7378

Abstract

Cancer is at present one of the utmost deadly diseases worldwide. Past efforts in cancer research have focused on natural medicinal products. Over the past decades, a great deal of initiatives was invested towards isolating and identifying new marine metabolites via pharmaceutical companies, [...] Read more.

Cancer is at present one of the utmost deadly diseases worldwide. Past efforts in cancer research have focused on natural medicinal products. Over the past decades, a great deal of initiatives was invested towards isolating and identifying new marine metabolites via pharmaceutical companies, and research institutions in general. Secondary marine metabolites are looked at as a favorable source of potentially new pharmaceutically active compounds, having a vast structural diversity and diverse biological activities; therefore, this is an astonishing source of potentially new anticancer therapy. This review contains an extensive critical discussion on the potential of marine microbial compounds and marine microalgae metabolites as anticancer drugs, highlighting their chemical structure and exploring the underlying mechanisms of action. Current limitation, challenges, and future research pathways were also presented. Full article

(This article belongs to the Special Issue Marine-Derived Products for Biomedicine)

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29 pages, 3490 KiB

Open AccessReview

Marine-Derived Polymers in Ionic Liquids: Architectures Development and Biomedical Applications

by Simone S. Silva, Joana M. Gomes, Luísa C. Rodrigues and Rui L. Reis

Mar. Drugs 2020, 18(7), 346; https://doi.org/10.3390/md18070346 - 30 Jun 2020

Cited by 22 | Viewed by 6338

Abstract

Marine resources have considerable potential to develop high-value materials for applications in different fields, namely pharmaceutical, environmental, and biomedical. Despite that, the lack of solubility of marine-derived polymers in water and common organic solvents could restrict their applications. In the last years, ionic [...] Read more.

Marine resources have considerable potential to develop high-value materials for applications in different fields, namely pharmaceutical, environmental, and biomedical. Despite that, the lack of solubility of marine-derived polymers in water and common organic solvents could restrict their applications. In the last years, ionic liquids (ILs) have emerged as platforms able to overcome those drawbacks, opening many routes to enlarge the use of marine-derived polymers as biomaterials, among other applications. From this perspective, ILs can be used as an efficient extraction media for polysaccharides from marine microalgae and wastes (e.g., crab shells, squid, and skeletons) or as solvents to process them in different shapes, such as films, hydrogels, nano/microparticles, and scaffolds. The resulting architectures can be applied in wound repair, bone regeneration, or gene and drug delivery systems. This review is focused on the recent research on the applications of ILs as processing platforms of biomaterials derived from marine polymers. Full article

(This article belongs to the Special Issue Marine-Derived Products for Biomedicine)

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24 pages, 2153 KiB

Open AccessReview

Mexican Microalgae Biodiversity and State-Of-The-Art Extraction Strategies to Meet Sustainable Circular Economy Challenges: High-Value Compounds and Their Applied Perspectives

by Juan Eduardo Sosa-Hernández, Kenya D. Romero-Castillo, Lizeth Parra-Arroyo, Mauricio A. Aguilar-Aguila-Isaías, Isaac E. García-Reyes, Ishtiaq Ahmed, Roberto Parra-Saldivar, Muhammad Bilal and Hafiz M. N. Iqbal

Mar. Drugs 2019, 17(3), 174; https://doi.org/10.3390/md17030174 - 18 Mar 2019

Cited by 41 | Viewed by 8248

Abstract

In recent years, the demand for naturally derived products has hiked with enormous pressure to propose or develop state-of-the-art strategies to meet sustainable circular economy challenges. Microalgae possess the flexibility to produce a variety of high-value products of industrial interests. From pigments such [...] Read more.

In recent years, the demand for naturally derived products has hiked with enormous pressure to propose or develop state-of-the-art strategies to meet sustainable circular economy challenges. Microalgae possess the flexibility to produce a variety of high-value products of industrial interests. From pigments such as phycobilins or lutein to phycotoxins and several polyunsaturated fatty acids (PUFAs), microalgae have the potential to become the primary producers for the pharmaceutical, food, and agronomical industries. Also, microalgae require minimal resources to grow due to their autotrophic nature or by consuming waste matter, while allowing for the extraction of several valuable side products such as hydrogen gas and biodiesel in a single process, following a biorefinery agenda. From a Mexican microalgae biodiversity perspective, more than 70 different local species have been characterized and isolated, whereas, only a minimal amount has been explored to produce commercially valuable products, thus ignoring their potential as a locally available resource. In this paper, we discuss the microalgae diversity present in Mexico with their current applications and potential, while expanding on their future applications in bioengineering along with other industrial sectors. In conclusion, the use of available microalgae to produce biochemically revenuable products currently represents an untapped potential that could lead to the solution of several problems through green technologies. As such, if the social, industrial and research communities collaborate to strive towards a greener economy by preserving the existing biodiversity and optimizing the use of the currently available resources, the enrichment of our society and the solution to several environmental problems could be attained. Full article

(This article belongs to the Special Issue Marine-Derived Products for Biomedicine)

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