Marine Fungi Research Articles

Recent Updates on the Secondary Metabolites from Fusarium Fungi and Their Biological Activities (Covering 2019 to 2024)

Fusarium species are commonly found in soil, water, plants, and animals. A variety of secondary metabolites with multiple biological activities have been recently isolated from Fusarium species, making Fusarium fungi a treasure trove of bioactive compounds. This mini-review comprehensively highlights the newly isolated secondary metabolites produced by Fusarium species and their various biological activities reported from 2019 to October 2024. About 276 novel metabolites were revealed from at least 21 Fusarium species in this period. The main metabolites were nitrogen-containing compounds, polyketides, terpenoids, steroids, and phenolics. The Fusarium species mostly belonged to plant endophytic, plant pathogenic, soil-derived, and marine-derived fungi. The metabolites mainly displayed antibacterial, antifungal, phytotoxic, antimalarial, anti-inflammatory, and cytotoxic activities, suggesting their medicinal and agricultural applications. This mini-review aims to increase the diversity of Fusarium metabolites and their biological activities in order to accelerate their development and applications.

Aromatic polyketides isolated from the marine-derived fungus Didymella aeria and their neuroprotective activity.

Two novel aromatic polyketides, penicanesins J and K (1, 2), were isolated from the marine-derived fungus Didymella aeria, along with the known compound integrastatin B (3). The structures of the new compounds were determined by NMR spectroscopy and synthetic methods. The isolated compounds were tested for monoamine oxidase (MAO) B inhibition, anti-amyloid beta (Aβ) aggregation, and protective activity against H2O2-induced cell death in human neuroblastoma SH-SY5Y cells. Integrastatin B (3) showed potential activity for inhibition of Aβ aggregation and protection against H2O2-induced cell death.

Marine-derived fungi from the genus Aspergillus (Ascomycota) and their anticancer properties

Marine-derived fungi from the genus <i>Aspergillus</i> (Ascomycota) and their anticancer properties

Isolation of marine-derived filamentous fungi and their potential application for bioremediation process.

We evaluated the bioremediation potential of petroleum-derived compounds using fungal strains isolated from marine samples collected on the coast of the states of Paraná, Brazil. About 75 isolated filamentous fungi were subjected to assays including decolorization of the synthetic dye Remazol Brilliant Blue R (RBBR), tolerance to diesel oil, production of bioemulsifying and degradation of pyrene. Nine isolates could decolorize RBBR between 3.4% and 88.16%. Ten were able to tolerate diesel oil and/or pyrene. One isolate was able to produce compounds with emulsifying properties. Three strains, Trichoderma sp. FM14 (Penicillium spp. FM02 and FM16, and FM14) were able to degrade pyrene between 33.0 and 42.4%, after 8 days. The results of the present work encourage future studies to optimize enzymatic conditions using isolates with biotechnological potential in bioremediation studies of marine environments contaminated with industrial pollutants including hydrocarbons derived from petroleum such as diesel oil and PAHs and synthetic dyes.

Retrosynthetic Pathways of Decahydrofluorene-Alkaloid Microascones B

Microascones B is a compound that can be a candidate for antibacterial material and is discovered and obtained from marine-derived fungus with complex 12- or 13- membered ring structures. Since no one has provided the forward synthesis and retrosynthesis pathway, we have introduced a possible retro-synthesis pathway in this work. The retrosynthesis of this complicated compound can be done in several steps into starting materials. Some of the core retrosynthesis strategies contain the analysis of di-oxygenation patterns to break bonds retro-synthetically by applying aldol reactions and Grignard as well as anion addition. Moreover, the Diels-Alder reaction is also one of the core reactions to break those multiple rings in this retrosynthesis pathway

Antibacterial Indole-Diterpenoid Alkaloids from the Marine Fungus Penicillium sp. ZYX-Z-718.

Two new indole-diterpenoids, penpaxilloids F and G (1 and 2), along with 11 known analogues (3-13), were isolated from the marine fungus Penicillium sp. ZYX-Z-718. The structures of the new compounds were identified by extensive spectroscopic analyses including HR-ESI-MS, UV, and NMR, as well as theoretical NMR chemical shifts and ECD calculations. Compounds 6 and 10 showed antibacterial activity against Gram-positive bacteria including Staphylococcus aureus, Bacillus subtilis, and MRSA with MIC values ranging from 16.0-32.0 μg/mL.

Sinulariapeptide F, a new peptide from culture broth of marine-derived fungus Simplicillium sp. SCSIO 41222.

One new compound named sinulariapeptide F (1) together with one known butyrolactone (2) and seven known peptides (3-9) were isolated from the fungus Simplicillium sp. SCSIO 41222. Their structures and absolute configurations were established using HRESIMS, NMR spectroscopy (1H, 13C, HSQC, HMBC) and marfey's method. All of these compounds were assessed their inhibitory activity of acetylcholinesterase (AChE) and pancreatic lipase (PL). Compounds 4 and 6 were selected to test for the inhibitory activity against programmed cell death-1 (PD-1)/ programmed cell death-ligand 1 (PD-L1). The results indicated that compound 4 displayed potent inhibition activity against PD-1/ PD-L1 with an IC50 value of 0.656 μM. Furthermore, the docking analysis demonstrated the interactions between 4 and proteins, suggesting PD-L1 to be a probable target for compound 4.

Penicitrisochromans A-C, new isochromans from the marine-derived fungus Penicillium citrinum PSU-MF100.

Three new isochroman derivatives, penicitrisochromans A-C (1-3), together with 25 known polyketides were isolated from the marine-derived fungus Penicillium citrinum PSU-MF100. Their structures were elucidated by extensive spectroscopic analysis. The absolute configurations of 1 and 2 were established by comparison of specific rotations and electronic circular dichroism (ECD) data with those of the known co-metabolite whereas those of 3 were assigned based on the ECD calculation and biosynthetic consideration. Among the isolated polyketides, three known anthraquinone derivatives, ω-hydroxyemodin, penicillanthranin A and emodin, displayed moderate to strong antibacterial activity against methicillin-resistant Staphylococcus aureus with MIC values of 32, 16 and 4 µg/mL, respectively. For antifungal activity, two known benzopyranones, coniochaetones A and C, exhibited moderate antifungal activity against Candida albicans NCPF3153 and Cryptococcus neoformans ATCC90112 with the respective MIC values of 16 and 64 µg/mL.

New indole-diterpenoids with protein tyrosine phosphatase inhibitory activity from a marine-derived fungus Penicillium janthinellum

Two new indole-diterpenes, janthinellumines J and K (1 and 2), and four analogues (3–6), were obtained from a marine-derived strain of the fungus Penicillium janthinellium. Among them, compound 1 represent the rare series of 1,2-seco-indole-diterpene from nature. Due to the distance between the stereogenic centers of C-23 and C-3/C-4/C-7/C-9/C-13/C-16, the determination of the configuration of 1 posed a considerable challenge. To solve this problem, the analysis of extensive spectroscopic data and calculated ECD and VCD methods were carried out for the new compound. Compounds 1 and 2 showed potent protein tyrosine phosphatase (PTP) inhibitory activity against PTP1B, TCPTP, SHP1, SHP2, and CD45 with IC50 values ranging from 3.3 to 23.1 μg/mL. Furthermore, the mechanism of PTP inhibitory activity of 1 and 2 was investigated using molecular docking method.

Talaroterpenoids A-F: Six New Seco-Terpenoids from the Marine-Derived Fungus Talaromyces aurantiacus.

Six new highly oxidized seco-terpenoids, including three 3-nor-labdane type diterpenes, talaroterpenoids A-C (1-3), and three meroterpenoids containing an orthoester group, talaroterpenoids D-F (6-8), together with five known compounds (4-5 and 9-11), were isolated from the marine-derived fungus Talaromyces aurantiacus. Their chemical structures were elucidated through 1D, 2D NMR, HRESIMS, J-based configuration analysis (JBCA), computational ECD calculations, and single-crystal X-ray diffraction analysis. Compounds 1 and 2 contain an unusual 6,20-γ-lactone-bridged scaffold. Compounds 10 and 11 presented inhibitory effects on NO release in lipopolysaccharide (LPS)-induced BV-2 cells with IC50 values of 11.47 and 11.32 μM, respectively. Talaroterpenoid C (3) showed moderate antifungal activity against A. alternata and P. theae Steyaert.

Penisimplinoids A-K, highly oxygenated andrastin-type meroterpenoids with diverse activities from the marine-derived fungus Penicillium simplicissimum

Penisimplinoid A (1), the first andrastin-type meroterpenoid with an unprecedented 6/6/3/6/5/5 polycyclic systems, together with ten highly oxygenated andrastin-type meroterpenoids (2–11) and one known analogue (12), were co-isolated from the marine-derived fungus Penicillium simplicissimum. Their absolute configurations were determined by single-crystal X-ray diffraction analysis (Cu Kα), DP4+ probability analyses, and ECD quantum chemistry calculations. Biological evaluation revealed that 7 and 12 showed anti-inflammatory activities in the zebrafish assay, 6 exhibited cytotoxic activity against NCI-H446 tumor cells with an IC50 value of 6.49 μM, 7 and 11 exhibited significant promoting angio-genesis activities.

Chemical Diversity of Aspergillus alliaceus Phenotypes: Discovery of Brominated Bianthrones with Activity against Triple-Negative Breast Cancer Cell Lines.

Marine-derived fungi have emerged as a source for novel metabolites with a broad range of bioactivities. However, accessing the full potential of fungi under standard laboratory conditions remains challenging. LC-MS-based metabolomics in combination with varied culture conditions is a fast and powerful tool to detect new metabolites. Here, three developmental forms of the marine-derived fungus Aspergillus alliaceus were analyzed and 14 fungal metabolites, including new brominated polyketides (11-14) were isolated. Structure elucidation relied mainly on 1D and 2D NMR techniques and was supported by low- and high-resolution mass spectrometry and DFT-based computations. We sequenced the A. alliaceus genome, identified the bianthrone-producing biosynthetic gene cluster, and conducted expression analysis on genes involved in sexual development and biosynthesis. The NCI-60 cell line panel revealed selective in vitro activity against triple-negative breast cancer (TNBC) for the halogenated allianthrones and their full antiproliferative and cytotoxic effects were evaluated in five TNBC cell lines.

Bioprospecting of Marine Fungi for Production of Extracellular Protease

Proteases from microorganisms have attracted much attention in the last decade because of their gigantic potential in various industrial processes due to their proteolytic activity such as detergent, textile, leather, dairy, and pharmaceutical preparations. However, proteolytic enzymes from microorganisms are preferred in the industrial application of enzymes due to their technical and economic advantages. In the present research work, protease-producing microorganisms were isolated from marine soil samples and screened for protease-producing ability using skim milk agar. Among twenty-three isolates, nine isolates were protease positive indicated by the clear zone around the colony. In quantitative screening, the highest protease activity was observed with JML 15 (144.72 U/ml) and JML 8 (107.92 U/ml) and selected for further investigation. Based on the molecular characterization and phylogenetic studies, the selected isolates were identified as Penicillium lagena JML 8 (PP987316.1) and Penicillium oxalicum JML 15 (PQ160092.1). The results showed that JML 15 and JML 8 had great potential to be used for the production of protease enzymes and upscale for industrial production.

Design, synthesis and biological evaluation of marine naphthoquinone-naphthol derivatives as potential anticancer agents

1’-Hydroxy-4’,8,8’-trimethoxy-[2,2’-binaphthalene]-1,4-dione (compound 5), a secondary metabolite recently discovered in marine fungi, demonstrates promising cytotoxic and anticancer potential. However, knowledge regarding the anticancer activities and biological mechanisms of its derivatives remains limited. Herein, a series of novel naphthoquinone-naphthol derivatives were designed, synthesised, and evaluated for their anticancer activity against cancer cells of different origins. Among these, Compound 13, featuring an oxopropyl group at the ortho-position of quinone group, exhibited the most potent inhibitory effects on HCT116, PC9, and A549 cells, with IC50 values decreasing from 5.27 to 1.18 μM (4.5-fold increase), 6.98 to 0.57 μM (12-fold increase), and 5.88 to 2.25 μM (2.6-fold increase), respectively, compared to compound 5. Further mechanistic studies revealed that compound 13 significantly induced cell apoptosis by increasing the expression levels of cleaved caspase-3 and reducing Bcl-2 proteins through downregulating the EGFR/PI3K/Akt signalling pathway, leading to the inhibition of proliferation in HCT116 and PC9 cells. The present findings suggest this novel naphthoquinone-naphthol derivative may hold potential as an anticancer therapeutic lead.

From marine neglected substrata new fungal taxa of potential biotechnological interest: the case of Pelagia noctiluca.

The marine environment is extremely complex and exerts strong evolutionary pressure often leading to the appearance of microbial strains with new metabolic competencies. Microorganisms in marine ecosystems are still largely unknown and should be explored and conserved for biodiversity preservation, possible ecosystem restoring, and other applications. Biodiversity conservation should become a basic ecological strategy of particular significance in relation to global change. In this context, the present research aimed at exploring the culturable mycobiota associated with the jellyfish Pelagia noctiluca, never studied before. In addition, the isolated strains were tested for potential application (antimicrobial activity and presence of genes related to the production of secondary metabolites). Five jellyfishes were collected in the coastal area of Giglio Island and processed to isolate epizoic fungi. The strains were identified using a polyphasic approach (morphological, physiological, and molecular) and their salt preference was also investigated. The antifungal and antibacterial activity were tested for each strain with agar plug diffusion test. The presence of some key genes related to the main pathways for the production of secondary metabolites in fungi, polyketide synthases (PKSs), and non-ribosomal peptide synthase (NRPSs), was also assessed. A total of 164 isolates were obtained; after the dereplication, 40 morphotypes, and 23 species were identified. The phylogenetic analyses suggested the presence of new taxa belonging to Pleosporales: two new genera and species, and a new species of Tamaricicola. The detected mycobiota showed a relatively high diversity, if compared to other epizoic fungal communities. All isolated strains were marine fungi as confirmed by their salt preference and marked euryhalinism. The genes related to the two main pathways for the production of secondary metabolites in fungi, PKSs and NRPSs, were identified in four and nine strains, respectively. The antimicrobial activity was revealed in 70% of the strains, including the new taxa. The abundance of bioactive strains may be related to the potential involvement of epizoic fungi in host defense strategies. Moreover, these strains could show a high potential for further biotechnological applications particularly in the case of new taxa. All strains are maintained in culture collections.

Prospecting Marine Natural Products as the Disease-Modifying Treatment of Alzheimer’s Diseases

Alzheimer's disease (AD) is a severe and high costs health problem all over the world. To date, there is no therapy capable of curing AD, making drug discovery a challenging and intriguing field to explore. Targeting marine natural products (MNPs) as a source of drug leads is a suitable choice considering the content of bioactive compounds and promising pharmacological benefits. This article aims to look at MNPs with prospects in several prime targets in AD pathology to cure AD. Marine vertebrates (fishes), marine invertebrates (sponges, tunicates, ascidian, clams, scallops, sand dollars, crabs, cockle, sea cucumber, shrimp, bryozoa, marine worm), algae/seaweed, and marine microorganisms (marine fungi, bacterium, dinoflagellata, microalgae) can be potentially used as disease-modifying treatments (DMTs) for AD. By targeting multiple aspects of AD pathology, these MNPs offer a multifaceted approach to treating and potentially modifying the disease course. This result is an intriguing gap for researchers in the discovery and development of new drugs that can improve AD pathology.

Three New Antibacterial Mycophenolic Acid Derivatives from the Marine-Derived Fungus Penicillium sp. HN-66.

Three new mycophenolic acid derivatives, penicacids L-N (1-3), together with four known analogues, were isolated from a fungus Penicillium sp. HN-66 derived from a South China Sea marine sediment. The structures of compounds 1-3 were determined on the basis of HR-ESI-MS, NMR (1H, 13C, HSQC and HMBC) data analyses, and comparison of optical rotations. Antimicrobial activities of 1-7 were tested. The results showed that compounds 1-3 and 5-7 had weak inhibitory effects against E. coli ATCC 25922 with the MIC values of 50 μg/mL.

Insights into lignin bioconversion: lignin-derived compounds treatment of a novel marine fungus K-2.

The potential for the efficient conversion of lignocellulosic biomass has been extensively explored to produce a wide range of bioproducts. Many approaches have been sought for the deep conversion of lignin to generate products that are toxin-free and beneficial for processing into high-value-added components. This study reported a fungus isolated from the deep sea with strong synthesis of multiple lignocellulases, conversion of lignin and guaiacol (0.1%) by 71.6% and 86.1% within 9 days at 30 °C respectively, and outstanding environmental adaptability (20-50 °C and pH 3-8). Metabolic pathway profiling showed that this fungus utilized lignin to rapidly activate multiple ring-opening reactions including the 2,3- and 3,4-cleavage pathways, with the 2,3-cleavage pathway predominating after 5 days. Conversion of metabolic intermediates confirmed the superb potential of this strain for lignin treatment. Meanwhile, its shikimic acid pathway was metabolically active under lignin. This further expands the potential to produce valuable bioproducts during lignin treatment, especially under ambient conditions, which can significantly enhance high-value precursor compound production. © 2024 Society of Chemical Industry.

Efficient biodegradation of poly(butylene adipate-co-terephthalate) in mild temperature by cutinases derived from a marine fungus

Poly(butylene adipate-co-terephthalate) (PBAT) waste gradually accumulates in the environment, posing ecological risks. Enzymatic hydrolysis holds great potential in the end-of-life management of PBAT, but reported enzymes require high reaction temperatures, limiting their practical industrial applications. In this study, we discovered that the marine fungus Alternaria alternata FB1 can efficiently degrade PBAT at 28 °C. Two cutinases designated as AaCut4 and AaCut10, were identified and verified as key enzymes responsible for this degradation process. Notably, the recombinant AaCut10 was able to depolymerize 82.14 % PBAT within 24 h and fully decompose it within 48 h at 37 °C. Through protein engineering, the yield of terephthalic acid monomer was increased to 96.01 %, highlighting its potential for facilitating PBAT upcycling. Furthermore, based on the investigation of the distribution patterns of PBAT hydrolases, novel degradative agents have been identified within unique ecological niches, leading to the establishment of a comprehensive screening repository of PBAT hydrolases. Overall, our study provides new candidates for enzymatic PBAT recycling with low energy consumption and offers insights into the PBAT degradation manner in ecosystems.

Butyrolactone-I from marine fungi alleviates intestinal barrier damage caused by DSS through regulating Lactobacillus johnsonii and its metabolites in the intestine of mice

Butyrolactone-I (BTL-1), a secondary metabolite from the marine fungus Aspergillus terreus, exhibits numerous biological activities. Previous research has indicated that Butyrolactone-I alleviates intestinal epithelial inflammation via the TLR4/NF-κB and MAPK pathways. However, the mechanisms underlying its protection against intestinal barrier damage remain unclear. This study aims to further elucidate these mechanisms. We observed that BTL-1 administration increased the abundance of Lactobacillus johnsonii (LJ) in both in vivo and in vitro experiments, prompting an investigation into the effects of LJ and its metabolites on DSS-induced inflammatory bowel disease (IBD). The results demonstrated that BTL-1 significantly upregulated tight junction (TJ) and adherens junction (AJ) proteins, maintained intestinal barrier integrity, and alleviated DSS-induced IBD in mice. These effects were associated with the proliferation of LJ and its metabolites, such as butyric and propionic acids, and the inhibition of the MAPK signaling pathway in the colon. Interestingly, administering LJ alone produced a protective effect against DSS-induced IBD similar to that observed with BTL-1. Furthermore, butyric acid, a metabolite of LJ, also upregulated TJ/AJ proteins in intestinal epithelial cells through the MAPK signaling pathway. Our findings suggest that BTL-1 regulates intestinal flora, promotes LJ proliferation, protects intestinal barrier integrity, increases the concentrations of butyric and propionic acids, and ultimately inhibits the activation of the MAPK signaling pathway in mice to alleviate IBD. Therefore, BTL-1 could potentially be used as a natural drug to prevent IBD and maintain intestinal flora balance. ImportanceWe explored how butyrolactone-I exerts a preventive effect on IBD through intestinal bacteria (Lactobacillus johnsonii).