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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (20 November 2025) | Viewed by 12610

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Dr. Biswajita Pradhan

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Guest Editor

1. Department of Biotechnology, Sangmyung University, Seoul 03016, Republic of Korea
2. Department of Botany, Model Degree College, Rayagada 765017, Odisha, India
Interests: microalgal and cyanobacterial natural products; isolation and characterization of bioactive compounds; phyto-chemicals; antioxidants; pharmaceuticals; nutraceuticals; therapeutical; anticancer; antidiabetic; antimicrobial; anti-inflammatory

Special Issue Information

Dear Colleagues,

This Special Issue, entitled “Recent Research of Natural Products from Microalgae and Cyanobacteria”, presents a comprehensive overview of the latest research advancements concerning the exploration of the diverse array of bioactive compounds. Microalgae and cyanobacteria are renowned for their vast biochemical diversity and their potential for producing valuable natural products. This Special Issue highlights the cutting-edge research exploring various aspects of microalgae and cyanobacteria, including cultivation techniques, isolation, and the characterization of bioactive compounds, as well as their potential applications in pharmaceutical, nutraceutical, cosmeceuticals, biofuels, and industrial fields. The Issue also focuses on elucidating the biological activities of crude extracts and identified compounds, including antioxidant, antibacterial, antiviral, antifungal, anticancer, antidiabetic, and anti-inflammatory activities. Through the collaboration of experts in the field, this Special Issue provides valuable insights into the potential of microalgae and cyanobacteria as sustainable sources of novel bioactive compounds, with diverse applications in biotechnology, medicine, therapeutics, and environmental sustainability.

Dr. Biswajita Pradhan
Guest Editor

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Keywords

marine and fresh water microalgal and cyanobacterial bioactive compounds
microalgal and cyanobacterial carotenoids, vitamins, phenolics, and phycobiliproteins
microalgal and cyanobacterial alkaloids
microalgal and cyanobacterial polysaccharides
microalgal and cyanobacterial peptides
microalgal and cyanobacterial polyphenols
microalgal and cyanobacterial antioxidants
microalgal and cyanobacterial pharmaceuticals
microalgal and cyanobacterial nutraceuticals
microalgal and cyanobacterial anti-inflammatory compounds
microalgal and cyanobacterial antimicrobial compounds
microalgal and cyanobacterial anticancer compounds
microalgal and cyanobacterial neuroprotective compounds
microalgal and cyanobacterial antiviral compounds
microalgal and cyanobacterial-derived anti-aging compounds
microalgal and cyanobacterial extracts

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Published Papers (7 papers)

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Research

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13 pages, 1633 KB

Open AccessArticle

The Yeast Saccharomyces cerevisiae as a Model to Study the Anti-Aging Activity of Phycocyanin

by Donata Cassamagnaghi, Stefania Citterio, Enzo Martegani and Sonia Colombo

Int. J. Mol. Sci. 2026, 27(2), 960; https://doi.org/10.3390/ijms27020960 - 18 Jan 2026

Viewed by 373

Abstract

We recently published that phycocyanin, a phycobiliprotein which accounts for up to 20% of Arthrospira platensis dry weight, has a powerful anti-aging effect, greatly extending the chronological life span (CLS) of yeast cells grown in synthetic-defined medium, both under caloric restriction (CR) conditions (0.2% glucose) or under non-CR conditions (2% glucose). In this study, to explore the molecular mechanisms underlying the effects of phycocyanin, we investigated its impact on key signaling pathways involved in aging. Specifically, we performed CLS experiments using ras2Δ and snf1Δ yeast mutants. The Snf1 pathway is known to promote longevity (anti-aging), whereas the Ras2/PKA pathway accelerates aging (pro-aging). We show that, while in the snf1Δ mutant the anti-aging effect of phycocyanin was still evident, in the ras2Δ mutant, phycocyanin did not appear to exert any anti-aging activity, leading us to hypothesize that the Ras2/PKA pathway may be essential to mediate the anti-aging effect of phycocyanin. To evaluate the activity of phycocyanin under different nutritional conditions, we performed the CLS experiment in a YPDA-rich medium. We show that in this medium, phycocyanin accelerated the chronological aging process of yeast cells, greatly decreasing the CLS, both when glucose was present at low (0.2%) or at high (2%) concentration. Our data suggest that Saccharomyces cerevisiae could serve as a model not only to investigate the anti-aging properties and targets of phycocyanin, but also its potential side effects, which are possibly present in higher eukaryotes under certain conditions. Full article

(This article belongs to the Special Issue Recent Research of Natural Products from Microalgae and Cyanobacteria)

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23 pages, 2464 KB

Open AccessArticle

Biosynthesis of UV-Absorbing Mycosporine-like Amino Acids and Transcriptomic Profiling of Differential Gene Expression in Green Microalga Under Abiotic Stresses

by Georgia Tsintzou, Evmorfia Bataka, Georgia Tagkalaki, Sofoklis Keisaris, Nikolaos Tsiropoulos, Nikolaos Labrou and Panagiotis Madesis

Int. J. Mol. Sci. 2026, 27(1), 537; https://doi.org/10.3390/ijms27010537 - 5 Jan 2026

Viewed by 529

Abstract

Microalgae display remarkable resilience to harsh environments, partly through the biosynthesis of diverse secondary metabolites. Cyanobacteria and red algae are well known to produce mycosporine-like amino acids (MAAs)—low-molecular-weight, water-soluble UV-absorbing compounds with anti-inflammatory, anticancer, and antimicrobial activities. By contrast, green microalgae typically lack detectable MAAs under standard conditions, and their responses under abiotic stress remain poorly characterized. Here, we investigated the freshwater green microalga Jaagichlorella luteoviridis grown under three stressors (salinity, heat, and UV) and assessed MAA induction. High-performance liquid chromatography (HPLC) revealed that stressed cultures accumulated multiple MAAs, whereas untreated controls showed no such accumulation. All stress treatments (UV, salinity, and heat) produced a substantial increase in peak intensity at 323–350 nm, whereas the control samples showed significantly lower absorption in this region. We also optimized an MAA extraction protocol suitable for “green” downstream applications in the pharmaceutical, nutraceutical, and cosmeceutical sectors and formulated an emulsion showing preliminary positive results and exhibiting an increased SPF index from 3.60 (control) to 3.78 when 0.2% MAA extract was added. Transcriptomic profiling against a reference genome revealed stress-specific differential gene expression and overexpression of specific genes of the MAA pathway, like ArioC and AroM/Aro1 SAM methyltransferases, thus identifying candidate targets for engineering enhanced MAA production. Given market demand for environmentally friendly and safe bioactives, microalgae represent a promising source of these valuable molecules. Full article

(This article belongs to the Special Issue Recent Research of Natural Products from Microalgae and Cyanobacteria)

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18 pages, 2558 KB

Open AccessArticle

Key Nutrient Drivers for Biomass and C-Phycocyanin Production in Spirulina sp. Revealed by Media Optimization

by Ivani Nurjannah, Toto Subroto, Ari Hardianto, Lucy Adinisa and Keiichi Mochida

Int. J. Mol. Sci. 2025, 26(21), 10425; https://doi.org/10.3390/ijms262110425 - 27 Oct 2025

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Abstract

Optimizing nutrient formulations is essential to improving the biomass yield and C-phycocyanin (C-PC) productivity of Spirulina sp., a cyanobacterium with wide-ranging applications in food, pharmaceutical, and biotechnological industries. This study evaluated the effects of macronutrient modifications on growth and pigment biosynthesis using a two-level full factorial design across eight Zarrouk-based formulations compared to the standard medium. Cultivation experiments were conducted in triplicate, and growth was evaluated using linear growth rate, maximum optical density (OD₆₈₀), and dry biomass, while C-PC was quantified in crude extracts (PCL), dried biomass (PCD), and the purity index (PI). Among the tested formulations, F2 (16 g/L NaHCO₃, 5 g/L NaNO₃, 0.25 g/L K₂HPO₄) achieved the highest biomass productivity, yielding a 37.6% increase in dry weight and a 38.1% improvement in daily productivity compared to the control. In contrast, F3 (16 g/L NaHCO₃, 5 g/L NaNO₃, 1 g/L K₂HPO₄) yielded the highest C-PC content, nearly doubling both PCL and PCD values and enhancing pigment purity by 40.2%. ANOVA and interaction analyses confirmed that carbon and nitrogen synergistically promoted biomass formation, while phosphorus had a strong effect on pigment biosynthesis through C:N:P interactions. These findings demonstrate that Spirulina sp. requires distinct nutrient balances for optimal growth and pigment formation. Formulation F2 is ideal for maximizing biomass productivity, whereas F3 is optimal for high-value C-PC production. The results provide a rational framework for designing nutrient-efficient cultivation systems to advance sustainable Spirulina-based biomanufacturing. Full article

(This article belongs to the Special Issue Recent Research of Natural Products from Microalgae and Cyanobacteria)

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14 pages, 1114 KB

Open AccessArticle

Deciphering Important Odorants in a Spirulina (Arthrospira platensis) Dietary Supplement by Aroma Extract Dilution Analysis Using Offline and Online Fractionation Approaches

by Aikaterina Paraskevopoulou, Veronika Mall, Theodoros M. Triantis, Triantafyllos Kaloudis, Anastasia Hiskia, Dimitra Dimotikali and Martin Steinhaus

Int. J. Mol. Sci. 2025, 26(14), 6767; https://doi.org/10.3390/ijms26146767 - 15 Jul 2025

Cited by 1 | Viewed by 1912

Abstract

Investigating the volatiles isolated from a commercial spirulina (Arthrospira platensis) dietary supplement by gas chromatography–olfactometry (GC–O) in combination with an aroma extract dilution analysis (AEDA) resulted in 29 odor events with flavor dilution (FD) factors between 8 and 2048. Identification experiments, including various offline and online fractionation approaches, led to the structure assignment of 30 odorants, among which the most potent were sweaty 2- and 3-methylbutanoic acid (FD 2048), roasty, earthy, shrimp-like 2-ethyl-3,5-dimethylpyrazine (FD 2048), vinegar-like acetic acid (FD 1024), and floral, violet-like β-ionone (FD 1024). Static headspace dilution analysis revealed sulfuric, cabbage-like methanethiol (FD factor ≥ 32) as an additional potent odorant. In summary, 31 important spirulina odorants were identified in this study, and 14 were reported for the first time as spirulina constituents. Our data will provide a basis for future odor optimization of spirulina-based food products. Full article

(This article belongs to the Special Issue Recent Research of Natural Products from Microalgae and Cyanobacteria)

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14 pages, 14978 KB

Open AccessArticle

Serum-Free Media Formulation Using Marine Microalgae Extracts and Growth Factor Cocktails for Madin-Darby Canine Kidney and Vero Cell Cultures

by Areumi Park, Yeon-Ji Lee, Eunyoung Jo, Gun-Hoo Park, Seong-Yeong Heo, Eun-Jeong Koh, Seung-Hong Lee, Seon-Heui Cha and Soo-Jin Heo

Int. J. Mol. Sci. 2024, 25(18), 9881; https://doi.org/10.3390/ijms25189881 - 12 Sep 2024

Cited by 2 | Viewed by 3108

Abstract

The development of serum-free media (SFM) is critical to advance cell culture techniques used in viral vaccine production and address the ethical concerns and contamination risks associated with fetal bovine serum (FBS). This study evaluated the effects of marine microalgal extracts and growth factor cocktails on the activity of Madin-Darby canine kidney (MDCK) and Vero cells. Five marine microalgal species were used: Spirulina platensis (SP), Dunaliella salina (DS), Haematococcus pluvialis (HP), Nannochloropsis salina (NS), and Tetraselmis sp. (TS). DS and SP extracts significantly increased the proliferation rate of both MDCK and Vero cells. DS had a proliferation rate of 149.56% and 195.50% in MDCK and Vero cells, respectively, compared with that in serum-free medium (SFM). Notably, DS and SP extracts significantly increased superoxide dismutase (SOD) activity, which was 118.61% in MDCK cells and 130.08% in Vero cells for DS, and 108.72% in MDCK cells and 125.63% in Vero cells for SP, indicating a reduction in intracellular oxidative stress. Marine microalgal extracts, especially DS and SP, are feasible alternatives to FBS in cell culture as they promote cell proliferation, ensure safety, and supply essential nutrients while reducing oxidative stress. Full article

(This article belongs to the Special Issue Recent Research of Natural Products from Microalgae and Cyanobacteria)

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Review

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27 pages, 1280 KB

Open AccessReview

Cyanobacteria-Derived Extracellular Vesicles: A Novel Frontier in Drug Delivery and Therapeutics

by Khalid A. Asseri, Krishnaraju Venkatesan, Yahya I. Asiri, Saud Alqahtani, Taha Alqahtani, Pooja Muralidharan, Shaimaa Elsayed Ramadan Genena, Durgaramani Sivadasan, Premalatha Paulsamy and Kumarappan Chidambaram

Int. J. Mol. Sci. 2026, 27(1), 4; https://doi.org/10.3390/ijms27010004 - 19 Dec 2025

Viewed by 861

Abstract

Cyanobacteria, known for their diverse and potent bioactive compounds, present a unique method for drug delivery via their extracellular vesicles (EVs), often described as exosome-like due to size and function but distinct in biogenesis. These naturally occurring vesicles, particularly those from cyanobacteria, are gaining attention as potential carriers for targeted drug delivery because of their biocompatibility, stability, and ability to encapsulate various bioactive compounds. However, cyanobacterial EVs remain underexplored as a dedicated nanocarrier platform, and their specific advantages and limitations relative to existing systems have not been systematically synthesized. This review explores the potential therapeutic uses of cyanobacterial EVs, emphasizing their roles in cancer treatment, antimicrobial therapies, neuroprotection, and immune modulation. We explore their biogenesis and structural features, comparing them to synthetic nanocarriers like polymeric nanoparticles and liposomes. The review also addresses the challenges of isolating and characterizing cyanobacterial EVs at scale and highlights the need for advancements in synthetic biology and genetic engineering to optimize their therapeutic potential. Despite these challenges, cyanobacterial EVs’ unique properties offer significant promise for advancing drug delivery systems and providing innovative solutions for treating complex diseases. Full article

(This article belongs to the Special Issue Recent Research of Natural Products from Microalgae and Cyanobacteria)

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19 pages, 2774 KB

Open AccessReview

Insufficient Acetyl-CoA Pool Restricts the Phototrophic Production of Organic Acids in Model Cyanobacteria

by Dawei You, Faiz Rasul, Tao Wang and Maurycy Daroch

Int. J. Mol. Sci. 2024, 25(21), 11769; https://doi.org/10.3390/ijms252111769 - 1 Nov 2024

Cited by 5 | Viewed by 2272

Abstract

Cyanobacteria are promising biological chassis to produce biochemicals such as carboxylic acids and their derivatives from CO₂. In this manuscript, we reflected on cyanobacterial acetyl-CoA pool and TCA cycle as an important source of precursor molecules for the biosynthesis of carboxylic acids such as 3-hydroxypropionate, 3-hydroxybutyrate, succinate, malate, fumarate and free fatty acids, each of which is an important platform chemical for bioeconomy. We further highlighted specific features of the cyanobacterial TCA cycle, how it differs in structure and function from widely described TCA cycles of heterotrophic model organisms, and methods to make it more suitable for the production of carboxylic acids from CO₂. Currently, the yields of these compounds are significantly lower than those in heterotrophic organisms and it was concluded that the primary cause of this can be attributed to the limited flux toward acetyl-CoA. Strategies like overexpressing pyruvate dehydrogenase complex or introducing synthetic bypasses are being explored to overcome these limitations. While significant progress has been made, further research is needed to enhance the metabolic efficiency of cyanobacteria, making them viable for the large-scale, sustainable production of carboxylic acids and their derivatives. Full article

(This article belongs to the Special Issue Recent Research of Natural Products from Microalgae and Cyanobacteria)

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