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Exploring Microorganisms and Their Bioactive Secondary Metabolites: From Nature to...
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Exploring Microorganisms and Their Bioactive Secondary Metabolites: From Nature to Application

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (27 February 2026) | Viewed by 8619

Special Issue Editors

Dr. Monika Elżbieta Jach

E-Mail Website
Guest Editor
Department of Molecular Biology, John Paul II Catholic University of Lublin, Konstantynów 1H, 20-708 Lublin, Poland
Interests: probiotics; psychobiotics; metabiotics; prebiotics; multimodal synergistic therapy
Special Issues, Collections and Topics in MDPI journals
Dr. Ewa Sajnaga

E-Mail Website
Guest Editor
Department of Biomedicine and Environmental Research, John Paul II Catholic University of Lublin, Konstantynów 1J, 20-708 Lublin, Poland
Interests: entomopathogenic bacteria; rhizobia; gut microbiota; host–symbiont interactions
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Adrian Wiater

E-Mail Website
Guest Editor
Department of Industrial and Environmental Microbiology, Institute of Biological Science, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland
Interests: biopolymers; polysaccharides with biological activity; prebiotics; oligosaccharides
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of Molecules focuses on microorganisms and their bioactive secondary metabolites, with the aim of exploring these natural treasure troves from their sources of origin to their innovative applications.

Microbes produce a wide range of bioactive compounds which perform specific biological functions, with great significance in various fields, including medicine and industry. This Special Issue covers a wide range of relevant topics, such as strategies for accessing new natural products, biosynthesis, chemical composition, biological activity, mechanisms of action and regulations. It also examines microbial secondary metabolites as a foundation for drug discovery to address challenges such as the antimicrobial resistance crisis. Furthermore, it highlights research into the application of these compounds in other sectors, e.g., agriculture, environmental remediation or food preservation. Research on promising new sources of chemical entities, such as unexplored microbial taxa or ecological niches, is of particular interest.

By highlighting the latest advances and opportunities in this field through a curated collection of original research articles and reviews, this Special Issue aims to provide valuable insights into microbial metabolism and the untapped potential of secondary metabolites as the basis for the development of novel biotechnological strategies and sustainable approaches to meet global needs.

Dr. Monika Elżbieta Jach
Dr. Ewa Sajnaga
Prof. Dr. Adrian Wiater
Guest Editors

Manuscript Submission Information

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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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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

  • natural products
  • bioactive compounds
  • microbial secondary metabolites
  • biological activity
  • chemical composition
  • biosynthetic pathways
  • strategies for discovery
  • mechanisms of action
  • biotechnological potential
  • therapeutic applications

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Related Special Issue

Published Papers (7 papers)

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Research

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12 pages, 1558 KB  
Article
Secondary Metabolites with Antithrombotic and Antioxidant Activities Derived from Cordyceps cicadae
by Xingze Hu, Guisheng Wang, Tao Chen, Xinyue Zhang, Jianying Wu, Guang Shao, Runlin Cai and Zhigang She
Molecules 2026, 31(3), 558; https://doi.org/10.3390/molecules31030558 - 5 Feb 2026
Viewed by 471
Abstract
Cordyceps cicadae, a medicinal and edible entomopathogenic fungus, has been widely used in traditional Chinese medicine for treating various ailments. This study aimed to validate its ethnopharmacological uses by investigating bioactive constituents and their antithrombotic and antioxidant activities. Through various chromatographic separations, [...] Read more.
Cordyceps cicadae, a medicinal and edible entomopathogenic fungus, has been widely used in traditional Chinese medicine for treating various ailments. This study aimed to validate its ethnopharmacological uses by investigating bioactive constituents and their antithrombotic and antioxidant activities. Through various chromatographic separations, one unreported flavonoid; quercetin-3-O-β-D-methylglucopyranoside (1); three known flavonoids (2–4); and one new dicarboxylic acid derivative, cicadae acid (5), were isolated from C. cicadae. Their chemical structures were elucidated by a comprehensive spectroscopic analysis (1D/2D NMR and HRESIMS), electronic circular dichroism (ECD) calculations, a DP4+ probability analysis, and the modified Mosher method. All compounds exhibited significant antithrombotic effects at a concentration of 20 μM in a zebrafish model. Compounds 1–4 exhibited potent antioxidant activity in the DPPH radical scavenging assay, with IC50 values ranging from 12.81 ± 3.42 to 20.16 ± 2.64 μM. These findings provide scientific evidence supporting the traditional application of C. cicadae, identifying specific flavonoids and dicarboxylic acids as potential therapeutic agents for thrombosis and oxidative stress-related disorders. Full article
(This article belongs to the Special Issue Exploring Microorganisms and Their Bioactive Secondary Metabolites: From Nature to Application)
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12 pages, 2715 KB  
Article
Genome-Driven Discovery of Anti-MDR Bacterial Heptapeptides from a Cold-Seep-Derived Bacillus Strain
by Hongcheng Li, Yongmeng Cheng, Kaishuai Xing, Wenli Li and Fei Xiao
Molecules 2026, 31(3), 547; https://doi.org/10.3390/molecules31030547 - 4 Feb 2026
Cited by 1 | Viewed by 639
Abstract
With the increasing emergence of multidrug-resistant (MDR) bacteria, there is an urgent need to discover new antibiotics. In this study, genome mining coupled with anti-bacterial assay guided the targeted isolation of two new heptapeptides nobilamide Q3 (1) and R3 (2 [...] Read more.
With the increasing emergence of multidrug-resistant (MDR) bacteria, there is an urgent need to discover new antibiotics. In this study, genome mining coupled with anti-bacterial assay guided the targeted isolation of two new heptapeptides nobilamide Q3 (1) and R3 (2). These compounds were identified as new stereoisomers of the known scaffold A-3302-B (3). The structures of these compounds were elucidated through a combination of MS, NMR spectroscopy and Marfey’s analysis. Anti-MDR bacterial assays showed that compounds 2 and 3 exhibited effective growth inhibition against the Gram-positive MDR bacterial strain Staphylococcus aureus CCARM 3090 with MIC values of 3.25–6.5 μg/mL. Notably, our study reveals stereochemistry-dependent differences in their antibacterial activities, providing new insights into the structure–activity relationship of this class of peptides. Finally, an analysis of the biosynthetic gene cluster responsible for their production was conducted. This study underscores the significance of exploring cold-seep environments as a reservoir for discovering new antibiotics and provides a structural starting point for the future optimization of antimicrobial peptides. Full article
(This article belongs to the Special Issue Exploring Microorganisms and Their Bioactive Secondary Metabolites: From Nature to Application)
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9 pages, 865 KB  
Article
Two New Andrastin-Type Meroterpenoids from Marine Sponge-Derived Fungus Botryosporium sp. S5I2-1
by Hui-Xian Liang, Wan-Ying Guo, Shi-Hai Xu and Bing-Xin Zhao
Molecules 2026, 31(2), 294; https://doi.org/10.3390/molecules31020294 - 14 Jan 2026
Viewed by 429
Abstract
Botryomeroterpenoids A (1) and B (2), two new andrastin-type meroterpenoids, along with two known analogues (3 and 4), were isolated from sponge-derived fungus Botryosporium sp. S5I2-1. Their structures were characterized by detailed spectroscopic analysis. Meanwhile, the absolute [...] Read more.
Botryomeroterpenoids A (1) and B (2), two new andrastin-type meroterpenoids, along with two known analogues (3 and 4), were isolated from sponge-derived fungus Botryosporium sp. S5I2-1. Their structures were characterized by detailed spectroscopic analysis. Meanwhile, the absolute configurations of 1 and 2 were elucidated by comparing experimental and calculated ECD spectra. Compounds 1 and 2 were the first examples of andrastin-type meroterpenoids isolated from this genus, especially Compound 1 which represented the initial instance of 18-norandrastin-type meroterpenoids. Furthermore, the antibacterial activities of all compounds were also evaluated. However, the results indicated that these compounds showed no significant inhibitory activity against the tested bacteria with minimum inhibitory concentration (MIC) values of 32–64 μg/mL. Full article
(This article belongs to the Special Issue Exploring Microorganisms and Their Bioactive Secondary Metabolites: From Nature to Application)
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23 pages, 795 KB  
Article
The Effect of Selenium Supplementation on Amino Acid Accumulation by the Yeast Saccharomyces cerevisiae and Rhodotorula glutinis
by Wioletta Sęk, Alicja Synowiec, Katarzyna Pobiega and Marek Kieliszek
Molecules 2026, 31(2), 254; https://doi.org/10.3390/molecules31020254 - 12 Jan 2026
Viewed by 609
Abstract
Selenium-enriched yeast is considered the most bioavailable dietary form of this trace element. It is already authorised for use in food and feed, making it a key vehicle for closing nutritional Se gaps worldwide. Understanding how selenium accumulation reshapes the amino-acid balance of [...] Read more.
Selenium-enriched yeast is considered the most bioavailable dietary form of this trace element. It is already authorised for use in food and feed, making it a key vehicle for closing nutritional Se gaps worldwide. Understanding how selenium accumulation reshapes the amino-acid balance of yeast biomass is crucial for diet-related health benefits and optimising biotechnological processes that rely on high-quality microbial protein. The effect of selenium on yeast amino-acid metabolism is an important area of research due to its potential applications in biotechnology and functional food production. In the presented work, changes in the amino acid profile and protein quality in Saccharomyces cerevisiae ATCC 7090 and Rhodotorula glutinis CCY 20-2-26 cells grown in the presence of different selenium concentrations (0–40 mg Se4+/L) for 24 and 48 h were analyzed. The amino acid content was assessed, and the Chemical Score (CS) and adjusted Essential Amino Acid Index (EAAI) were determined. The results showed that moderate selenium concentrations (2–10 mg Se4+/L after 24 h) promoted the accumulation of essential amino acids, such as lysine (53.3 mg/g) and valine (38.0 mg/g) in S. cerevisiae and lysine (42.8 mg/g) and valine (41.6 mg/g) in R. glutinis. High values of protein quality indices were also obtained under the same conditions—CS exceeding 200% and adjusted EAAI reaching 1.71 for S. cerevisiae and 2.05 for R. glutinis. It is worth noting, however, that EAAI was presented without methionine and tryptophan. In turn, higher selenium concentrations and longer cultivation time decreased these parameters, especially in the case of S. cerevisiae. The obtained data confirm that R. glutinis may be a promising source of high-quality protein in selenium-enriched products. Full article
(This article belongs to the Special Issue Exploring Microorganisms and Their Bioactive Secondary Metabolites: From Nature to Application)
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Review

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27 pages, 1125 KB  
Review
Fungal Secondary Metabolites in Bioelectrochemical Systems: A Bibliometric Analysis and Critical Review of Emerging Trends and Challenges for Sustainable Energy
by Segundo J. Rojas-Flores, Rafael Liza, Renny Nazario-Naveda, Félix Díaz, Daniel Delfin-Narciso and Moisés Gallozzo Cardenas
Molecules 2026, 31(4), 716; https://doi.org/10.3390/molecules31040716 - 19 Feb 2026
Viewed by 567
Abstract
The global energy crisis driven by an 80% reliance on fossil fuels and the urgent need to reduce greenhouse gas emissions demands the exploration of sustainable biotechnological alternatives. This study addresses a critical knowledge gap regarding the integration of fungal secondary metabolites into [...] Read more.
The global energy crisis driven by an 80% reliance on fossil fuels and the urgent need to reduce greenhouse gas emissions demands the exploration of sustainable biotechnological alternatives. This study addresses a critical knowledge gap regarding the integration of fungal secondary metabolites into bioelectrochemical energy systems, as these compounds have traditionally been investigated for pharmacological purposes. The methodology involved a documentary analysis using the Scopus database (2000–2025), applying a search equation that combined terms such as “secondary metabolite”, “fungi”, and “bioenergy”. Data processing was conducted using R Studio (R 3.6.0+), VOSviewer (1.6.20) for collaboration networks, and Plotly Studio (v6.5.0) for interactive visualizations. Key findings revealed that redox mediators such as quinones and organic acids derived from Aspergillus niger enhanced electron transfer efficiency by 35%, achieving power densities of 1.2 W/m2. Meanwhile, Penicillium chrysogenum reduced internal electrode resistance by 40%. Additionally, the “xeno-fungosphere” system achieved 97.9% herbicide removal and generated 9.3 µW/cm2. Notably, biosynthesized bis-quinones were successfully applied in redox flow batteries, reaching a capacity of 1.58 Ah/L. In conclusion, the study identified a scientific shift from pharmacological applications toward energy metabolism and sustainability, positioning fungi as critical components for the future efficiency of bioelectrical technologies. Full article
(This article belongs to the Special Issue Exploring Microorganisms and Their Bioactive Secondary Metabolites: From Nature to Application)
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38 pages, 2430 KB  
Review
Advances in Natural Products from Mangrove-Associated Fungi Along the Indian Ocean Coast
by Parakkrama Wijerathna, Xinqi Chen, Rongxiang Qiu, P.V.J.S. Wijethilake, Yi Chen, Nuwan Madushanka, I.J.J.U.N. Perera, Jian Cai, Lalith Jayasinghe, Yonghong Liu, Vajira P. Bulugahapitiya and Xuefeng Zhou
Molecules 2026, 31(2), 261; https://doi.org/10.3390/molecules31020261 - 12 Jan 2026
Cited by 4 | Viewed by 897
Abstract
Mangrove ecosystems along the Indian Ocean coast show great biodiversity, adapting to harsh environmental conditions of high salinity and higher organic matter, and they are a host for a range of microbial communities with special features that produce unique secondary metabolites. Of this, [...] Read more.
Mangrove ecosystems along the Indian Ocean coast show great biodiversity, adapting to harsh environmental conditions of high salinity and higher organic matter, and they are a host for a range of microbial communities with special features that produce unique secondary metabolites. Of this, mangrove-associated endophytic fungi, the second largest ecological group of marine fungi, show the greater potential, being a diverse pool for discovering novel bio-actives with pharmacological and biotechnological interest. This review summarizes the research findings on structural diversity and the associated pharmacological activities of secondary metabolites produced by mangrove-associated fungi along the Indian Ocean coast reported over the period of 2002–2025, based on the literature retrieved from Google Scholar. The total of 302 secondary metabolites is presented mainly from classes of polyketides (208), alkaloids (34), and terpenoids (60). Interestingly, 164 compounds were identified, as first reported in those publications. These compounds have been reported to show diverse biological activities, and the most prominent activities are cytotoxic, antibacterial, antifungal, antioxidant, enzyme inhibitory, and anti-inflammatory effects. The structural novelty and pharmacological activities of these metabolites highlight the importance of mangrove fungi as promising sources for new drug discovery and advancing industrial biotechnology. Therefore, this review highlights the insight into the possible application of these chemical compounds in the future drug industry, as well as in biotechnology for advancing human well-being. Furthermore, though significant progress has been made in exploring the fungi community from mangroves of the African and Middle Eastern coasts, the Indian coast mangrove fungi are yet to be explored more for novel discoveries. Full article
(This article belongs to the Special Issue Exploring Microorganisms and Their Bioactive Secondary Metabolites: From Nature to Application)
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37 pages, 1680 KB  
Review
The Role of Probiotics and Their Postbiotic Metabolites in Post-COVID-19 Syndrome
by Monika E. Jach, Ewa Sajnaga, Marharyta Bumbul, Anna Serefko, Kinga K. Borowicz, Hieronim Golczyk, Marek Kieliszek and Adrian Wiater
Molecules 2025, 30(20), 4130; https://doi.org/10.3390/molecules30204130 - 20 Oct 2025
Cited by 1 | Viewed by 4205
Abstract
Post-COVID-19 syndrome, also known as long-COVID, is characterized by a wide spectrum of persistent symptoms involving multiple body organs and systems, including fatigue, gastrointestinal disorders, and neurocognitive dysfunction. Emerging evidence suggests that gut microbiota dysbiosis and disruption of the gut–brain axis play a [...] Read more.
Post-COVID-19 syndrome, also known as long-COVID, is characterized by a wide spectrum of persistent symptoms involving multiple body organs and systems, including fatigue, gastrointestinal disorders, and neurocognitive dysfunction. Emerging evidence suggests that gut microbiota dysbiosis and disruption of the gut–brain axis play a central role in the pathophysiology of this condition. Probiotics and their metabolites (postbiotics) have gained increasing attention as potential therapeutic agents given their immunomodulatory, anti-inflammatory, and antiviral properties. In this review, we discuss the current understanding of the antiviral mechanisms of probiotics, including reinforcement of intestinal epithelial barrier function, direct virus inhibition, receptor competition, and immune system modulation. Special emphasis is placed on short-chain fatty acids (SCFAs), lactic acid, hydrogen peroxide, and bacteriocins as key factors that contribute to these effects. SCFAs appear to be essential postbiotic compounds during post-COVID recovery. We also highlight recent clinical trials involving specific probiotic species, such as Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Bifidobacterium longum, and their potential role in alleviating long-term COVID symptoms. Although the current results are promising, further research is needed to clarify the most effective strains, dosages, and mechanisms of action in post-COVID therapeutic strategies. Full article
(This article belongs to the Special Issue Exploring Microorganisms and Their Bioactive Secondary Metabolites: From Nature to Application)
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