Marine Fungi Research Articles

Bio-oxidation of progesterone by Penicillium oxalicum CBMAI 1185 and evaluation of the cytotoxic activity

We report the biotransformation of progesterone 1 by whole cells of Brazilian marine-derived fungi. A preliminary screening with 12 fungi revealed that the strains Penicillium oxalicum CBMAI 1996, Mucor racemous CBMAI 847, Cladosporium sp. CBMAI 1237, Penicillium oxalicum CBMAI 1185 and Aspergillus sydowii CBMAI 935 were efficient in the biotransformation of progesterone 1 in the first days of the reaction, with conversion values ranging from 75 % to 99 %. The fungus P. oxalicum CBMAI 1185 was employed in the reactions in quintuplicate to purify and characterize the main biotransformation products of progesterone 1. The compounds testololactone 1a, 12β-hydroxyandrostenedione 1b and 1β-hydroxyandrostenedione 1c were isolated and characterized by NMR, MS, [α]D and MP. In addition, the chromatographic yield of compound 1a was determined by HPLC-PDA in the screening experiments. In this study, we show a biotransformation pathway of progesterone 1, suggesting the presence of several enzymes such as Baeyer-Villiger monooxygenases, dehydrogenases and cytochrome P450 monooxygenases in the fungus P. oxalicum CBMAI 1185. In summary, the results obtained in this study contribute to the synthetic area and have environmental importance, since the marine-derived fungi can be employed in the biodegradation of steroids present in wastewater and the environment. The cytotoxic results demonstrate that the biodegradation products were inactive against the cell lines, in contrast to progesterone.

Planktonic Marine Fungi: A Review

AbstractFungi in marine ecosystems play crucial roles as saprotrophs, parasites, and pathogens. The definition of marine fungi has evolved over the past century. Currently, “marine fungi” are defined as any fungi recovered repeatedly from marine habitats that are able to grow and/or sporulate in marine environments, form symbiotic relationships with other marine organisms, adapt and evolve at the genetic level, or are active metabolically in marine environments. While there are a number of recent reviews synthesizing our knowledge derived from over a century of research on marine fungi, this review article focuses on the state of knowledge on planktonic marine fungi from the coastal and open ocean, defined as fungi that are in suspension or attached to particles, substrates or in association with hosts in the pelagic zone of the ocean, and their roles in remineralization of organic matter and major biogeochemical cycles. This review differs from previous ones by focusing on biogeochemical impacts of planktonic marine fungi and methodological considerations for investigating their diversity and ecological functions. Importantly, we point out gaps in our knowledge and the potential methodological biases that might have contributed to these gaps. Finally, we highlight recommendations that will facilitate future studies of marine fungi. This article first provides a brief overview of the diversity of planktonic marine fungi, followed by a discussion of the biogeochemical impacts of planktonic marine fungi, and a wide range of methods that can be used to study marine fungi.

Pannorin isolated from marine Penicillium sp. SG-W3: a selective monoamine oxidase A inhibitor

Six compounds were isolated from Penicillium sp. SG-W3, a marine-derived fungus, and their inhibitory activities against target enzymes relating to neurological diseases were evaluated. Compound 1 (pannorin) was a potent and selective monoamine oxidase (MAO)-A inhibitor with a 50% inhibitory concentration (IC50) of 1.734 μM and a selectivity index (SI) of > 23.07 versus MAO-B, and it showed an efficient antioxidant activity. All compounds showed weak inhibitory activities against acetylcholinesterase, butyrylcholinesterase, and β-secretase. The inhibition constant (Ki) of 1 for MAO-A was 1.049 ± 0.030 μM with competitive inhibition. Molecular docking simulation predicted that compound 1 forms hydrogen bonds with MAO-A, and binds more tightly to MAO-A than to MAO-B (− 25.02 and − 24.06 kcal/mol, respectively). These results suggest that compound 1 is a selective, reversible, and competitive MAO-A inhibitor that can be a therapeutic candidate for treating neurological diseases.

Secondary metabolites from marine fungi as anticandidia

Secondary metabolites from marine fungi as anticandidia

Microascones, Decahydrofluorene-Class Alkaloids from the Marine-Derived Fungus Microascus sp. SCSIO 41821.

Eight new decahydrofluorene-class alkaloids, microascones A and B (1 and 2), 2,3-epoxyphomapyrrolidone C (3), 14,16-epiascomylactam B (4), 24-hydroxyphomapyrrolidone A (5), and microascones C-E (6-8), along with five known analogs (9-13) were isolated from the marine-derived fungus Microascus sp. SCSIO 41821. Compounds 1 and 2 have an unprecedented complex macrocyclic alkaloid skeleton with a 6/5/6/5/6/5/13 polycyclic system. Their structures and absolute configurations were determined by spectroscopic analysis, quantum chemical calculations of ECD spectra, and 13C NMR chemical shifts. Compounds 10-13 showed selective enzyme inhibitory activity against PTPSig, PTP1B, and CDC25B, and 4, 9, and 10 exhibited strong antibacterial activity against seven tested pathogens. Their structure-bioactivity relationship was discussed, and a plausible biosynthetic pathway for 1-8 was also proposed.

Chemical Constituents of a Marine-derived Fungus Fusarium oxysporum F0888 and their Antibacterial Activity.

Five new compounds, including four hydroxyphenylacetic acid derivatives, stachylines H-K (1-4), a derivative of hydroxyphenylethanol (5), as well as seven known compounds were obtained from a marine-derived fungus Fusarium oxysporum F0888 isolated from sediments in the South China Sea. The structures and absolute configurations of new compounds were determined by spectroscopic (IR, NMR, and HR-ESI-MS) analyses, comparison of optical rotations, and the modified Mosher's MTPA ester method. Antimicrobial and anti-inflammatory activities of compounds 1-12 were tested. Unfortunately, all of isolated compounds were inactivity.

Marine-Derived Alternariol Monomethyl Ether Alleviates Ovalbumin-Induced Food Allergy by Suppressing MAPK and NF-κB Signaling Pathways of Mast Cells.

The prevalence of food allergies has grown dramatically over the past decade. Recently, studies have shown the potential of marine substances to alleviate food allergies. We utilized a rat basophilic leukemia (RBL)-2H3 model to evaluate the antiallergic effects of alternariol monomethyl ether (AME) extracted from marine fungi Alternaria sp. Our results showed that AME attenuated food allergy symptoms in mice and reduced histamine release in serum. The population of mast cells in the spleen and mesenteric lymph nodes was considerably reduced. Moreover, in vitro assays also revealed that AME inhibited the release of β-hexosaminidase and histamine. Transcriptomic analysis uncovered that AME regulated gene expression associated with mast cells. Additionally, Western blotting demonstrated that AME suppressed mast cell activation by modulating MAPK and NF-κB signaling pathways. Taken together, these findings provide a theoretical basis for the potential antiallergic use of marine-derived compounds in the development of functional foods.

HPPO-Derived Meroterpenoids from the Marine-Derived Fungus Penicillium sp. SCSIO 41691.

Seven new 4-hydroxy-6-phenyl-2H-pyran-2-one (HPPO) derived meroterpenoids, 1-methyl-12a,12b-epoxyarisugacin M (1), 1-methyl-4a,12b-epoxyarisugacin M (2), 2,3-dihydroxy-3,4a-epoxy-12a-dehydroxyisoterreulactone A (3), 2-hydroxy-12a-dehydroxyisoterreulactone A (4), 3'-demethoxyterritrems B' (5), 4a-hydroxyarisugacin P (6), and 1-epi-arisugacin H (7), together with two known analogues (8 and 9), were isolated from the marine-derived fungal strain Penicillium sp. SCSIO 41691. Their structures were elucidated by spectroscopic methods, and the absolute configurations of compounds 1 and 3 were determined by single-crystal X-ray diffraction. Among them, 1 and 2 had a unique methyl migration in the basic meroterpenoid skeleton with a 12a,12b-epoxy or 4a,12b-epoxy group, and 3 was a highly oxygenated HPPO-derived meroterpenoid featuring a rare 6/5/6/6/6/6 hexacyclic system with a 3,4a-epoxy group. Biologically, 5 exhibited inhibitory activity against lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells with an IC50 value of 21 μM, more potent than the positive control indomethacin.

Antimicrobial activity assessment of crude broth fermented extracts of marine-derived fungi collected from Bai Tu Long bay (North Vietnam)

This study aimed to isolate and identify marine fungi from Bai Tu Long Bay and assess their antimicrobial potential. We successfully isolated twenty strains of marine-derived fungi. The crude extracts from these fungi were tested against pathogenic microorganisms. All twenty strains exhibit some degree of growth inhibition against the tested microorganisms. Notably, strains M223, M250, M253, and M256 showed significant antimicrobial activity, with MIC values equal to or lower than the positive control. These results highlight the potential of marine fungi as a rich source of antimicrobial agents, a finding of considerable importance to marine mycology and pharmaceuticals. Further analysis was conducted on four promising isolates. M253 was identified as Hamigera avellanea, while M223, M250, and M256 were found to belong to the Aspergillus genus. These isolates were then analyzed using a phylogenetic tree based on MegaX software.

A MassQL-Integrated Molecular Networking Approach for the Discovery and Substructure Annotation of Bioactive Cyclic Peptides.

The marine sponge-derived fungus Stachylidium bicolor 293 K04 is a prolific producer of specialized metabolites, including certain cyclic tetrapeptides called endolides, which are characterized by the presence of the unusual amino acid N-methyl-3-(3-furyl)-alanine. This rare feature can be used as bait to detect new endolide-like analogs through customized fragment pattern searches of tandem mass spectrometry data using the Mass Spec Query Language (MassQL). Here, we integrate endolide-specific MassQL queries with molecular networking to obtain substructural information guiding the targeted isolation and structure elucidation of the new proline-containing endolides E (1) and F (2). We showed that endolide F (but not E) is a moderate antagonist of the arginine vasopressin V1A receptor, a member of the G protein-coupled receptor superfamily.

A simulation-based approach to target Zika virus RNA-dependent RNA polymerase with marine compounds for antiviral development

Despite significant efforts, currently, there is no particular drug available to treat Zika virus (ZIKV) infection, highlighting the urgent need for effective therapeutic interventions. To identify putative inhibitors of the ZIKV RdRp protein’s RNA binding function, the present study applied an extensive in-silico drug discovery methodology. The initial phase involved virtual screening using Lipinski’s rule of five as a filter, ensuring the selection of molecules with favorable pharmacokinetic properties. This process yielded 238 compounds with promising docking scores, ranging from −6.0 to −7.48 kcal/mol, indicative of their potential binding affinity to the ZIKV RdRp. To refine the selection, these compounds underwent a re-docking process, comparing their binding energies with a reference molecule known for its inhibitory action against RdRp. Remarkably, five compounds, labeled CMNPD30598, CMNPD27464, CMNPD25971, CMNPD27444, and CMNPD16599, demonstrated superior re-docking energies compared to the reference, suggesting a stronger interaction with the RdRp allosteric site. Subsequent molecular dynamics (MD) simulations provided insights into the stability of these complexes over time, reinforcing their potential as RdRp inhibitors. Additionally, the calculation of free binding energies and principal component analysis (PCA) of the free energy landscape offered a deeper understanding of the binding dynamics and energetics. This study not only highlights the utility of marine fungi compounds in antiviral drug discovery but also showcases the power of computational tools in identifying novel therapeutics. The identified compounds represent promising candidates for further experimental validation and development as ZIKV RdRp inhibitors. Communicated by Ramaswamy H. Sarma

Hydroxytakakiamide and Other Constituents from a Marine Sponge-Associated Fungus Aspergillus fischeri MMERU23, and Antinociceptive Activity of Ergosterol Acetate, Acetylaszonalenin and Helvolic Acid.

An unreported prenylated indole derivative hydroxytakakiamide (4) was isolated, together with the previously described ergosterol (1), ergosterol acetate (2), and (3R)-3-(1H-indol-3-ylmethyl)-3, 4-dihydro-1H-1,4-benzodiazepine-2,5-dione (3), from the column fractions of the crude ethyl acetate extract of the culture of a marine sponge-associated fungus, Aspergillus fischeri MMERU 23. The structure of 4 was elucidated by the interpretation of 1D and 2D NMR spectral data and high-resolution mass spectrum. The absolute configuration of the stereogenic carbon in 3 was proposed to be the same as those of the co-occurring congeners on the basis of their biogenetic consideration and was supported by the comparison of its sign of optical rotation with those of its steroisomers. The crude ethyl acetate extract and 2 were evaluated, together with acetylaszonalenin (5) and helvolic acid (6), which were previously isolated from the same extract, for the in vivo antinociceptive activity in the mice model. The crude ethyl acetate extract exhibited antinociceptive activity in the acetic acid-induced writhing and formalin tests, while 2, 5, and 6 displayed the effects in the late phase of the formalin test. On the other hand, neither the crude ethyl acetate extract nor 2, 5, and 6 affected the motor performance of mice in both open-field and rotarod tests. Additionally, docking studies of 2, 5, and 6 were performed with 5-lipoxygenase (5-LOX) and phosphodiesterase (PDE) enzymes, PDE4 and PDE7, which are directly related to pain and inflammatory processes. Molecular docking showed that 6 has low affinity energy to PDE4 and PDE7 targets while retaining high affinity to 5-LOX. On the other hand, while 2 did not display any hydrogen bond interactions in any of its complexes, it achieved overall better energy values than 6 on the three antinociceptive targets. On the other hand, 5 has the best energy profile of all the docked compounds and was able to reproduce the crystallographic interactions of the 5-LOX complex.

Austin-Type Meroterpenoids from Fungi Reported in the Last Five Decades: A Review.

Austin was first isolated as a novel polyisoprenoid mycotoxin from Aspergillus ustus in 1976. Subsequently, some new austin-type meroterpenoids (ATMTs) have been continually found. This review attempts to give a comprehensive summary of progress on the isolation, chemical structural features, biological activities, and fungal biodiversity of 104 novel ATMTs from 5 genera of terrestrial- and marine-derived fungi reported from October 1976 to January 2023. The genera of Penicillium and Aspergillus are the two dominant producers, producing 63.5% and 30.8% of ATMTs, respectively. Moreover, about 26.9% of ATMTs display various pronounced bioactivities, including insecticidal, anti-inflammatory, cytotoxicity, antibacterial, and PTP1B inhibitory activities. The chemical diversity and potential activities of these novel fungal ATMTs are reviewed for a better understanding, and a relevant summary focusing on the source fungi and their taxonomy is provided to shed light on the future development and research of austin-type meroterpenoids.

The Use of Marine Mushroom Extract (Nodulisporium sp.) as Feed Additive in the Ration of Native Chickens on Protein Utilisation Ratio

Feed plays an important role in the growth process of native chickens. This research aims to determine the effect of using marine fungi extract (Nodulispolium sp.) as a feed additive in native chicken rations on the protein utilization ratio. This research was a collaboration between the IPB University and Jambi University which used 180 unsexing DOC native chickens and marine fungi extract. The design used was a Completely Randomized Design (CRD) consisting of 5 treatments and 4 replications. The treatments were P0 = Basal Ration (control), P1 = P0 + 1 ml marine fungi extract/kg, P2 = P0 + 2 ml marine fungi extract/kg, P3 = P0 + 3 ml marine fungi extract/kg and P4 = P0 + 4 ml marine fungi extract/kg. The variables observed included dry matter consumption, crude protein consumption, body weight gain and protein utilization ratio. Data were analyzed using analysis of variance (ANOVA) and the differences between treatments, adding were tested using Duncan's Multiple Range Test. The results of analysis of variance showed that the use of marine fungi extract as a feed additive in rations up to 4 ml/kg ration had no significant effect (P>0.05) on dry matter consumption, crude protein consumption, body weight gain and protein utilization ratio. It can be concluded that the use of marine fungi extract as a feed additive in rations up to 4 ml/kg has not been able to increase the protein ratio chickens

Anti-diabetic and anti-inflammatory indole diterpenes from the marine-derived fungus Penicillium sp. ZYX-Z-143

Seven new indole-diterpenoids, penpaxilloids A–E (1–5), 7-methoxypaxilline-13-ene (6), and 10-hydroxy-paspaline (7), along with 20 known ones (8–27), were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Among them, compound 1 was a spiro indole-diterpenoid bearing a 2,3,3a,5-tetrahydro-1H-benzo[d]pyrrolo[2,1–b][1,3]oxazin-1-one motif. Compound 2 was characterized by a unique heptacyclic system featuring a rare 3,6,8-trioxabicyclo[3.2.1]octane unit. The structures of the new compounds were established by extensive spectroscopic analyses, NMR calculations coupled with the DP4 + analysis, and ECD calculations. The plausible biogenetic pathway of two unprecedented indole diterpenoids, penpaxilloids A and B (1 and 2), was postulated. Compound 1 acted as a noncompetitive inhibitor against protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 8.60 ± 0.53 μM. Compound 17 showed significant α-glucosidase inhibitory activity with IC50 value of 19.96 ± 0.32 μM. Moreover, compounds 4, 8, and 22 potently suppressed nitric oxide production on lipopolysaccharide-stimulated RAW264.7 macrophages.

Meirols A-C: Bioactive Catecholic Compounds from the Marine-Derived Fungus Meira sp. 1210CH-42.

Three new catecholic compounds, named meirols A-C (2-4), and one known analog, argovin (1), were isolated from the marine-derived fungus Meira sp. 1210CH-42. Their structures were determined by extensive analysis of 1D, 2D NMR, and HR-ESIMS spectroscopic data. Their absolute configurations were elucidated based on ECD calculations. All the compounds exhibited strong antioxidant capabilities with EC50 values ranging from 6.01 to 7.47 μM (ascorbic acid, EC50 = 7.81 μM), as demonstrated by DPPH radical scavenging activity assays. In the α-glucosidase inhibition assay, 1 and 2 showed potent in vitro inhibitory activity with IC50 values of 184.50 and 199.70 μM, respectively (acarbose, IC50 = 301.93 μM). Although none of the isolated compounds exhibited cytotoxicity against one normal and six solid cancer cell lines, 1 exhibited moderate cytotoxicity against the NALM6 and RPMI-8402 blood cancer cell lines with GI50 values of 9.48 and 21.00 μM, respectively. Compound 2 also demonstrated weak cytotoxicity against the NALM6 blood cancer cell line with a GI50 value of 29.40 μM.

Exploitation of mangliculous marine fungi, Amarenographium solium, for the green synthesis of silver nanoparticles and their activity against multiple drug-resistant bacteria

Abstract The green synthesis pathway for silver nanoparticles (AgNPs) used in bacterial treatment is regarded as crucial because of its cost-effectiveness, nontoxicity, and eco-friendliness. During the present work, the mangliculous marine fungi Amarenographium solium isolated from the Arabian Gulf Coast of Saudi Arabia were utilized for the synthesis of AgNP, through the bio-reduction of aqueous silver nitrate (AgNO3) solution. The success in AgNP synthesis was visually identified by the development of dark brown color in the cell-free filtrate and was further confirmed by ultraviolet–visible spectroscopy, which showed a peak at 425 nm. The AgNPs produced were further characterized using X-ray diffraction data analysis that proved the bioreduction of silver to 20 nm, and transmission electron microscopy revealed the formation of well-dispersed spherical nanoparticles with an average mean size of 12 nm. The optimization reaction parameters of temperature, pH, and metal salt concentration were carried out and resulted in a combination of 30°C, 7 and 1.5 mM, respectively, for rapid and maximum yield production. The antibacterial activity of the produced nanoparticles was evaluated using the two-fold microdilution method and showed a minimum inhibitory concentration of 9.375 μg/mL of AgNP against multiple drug-resistant bacterial strains.

Novel anti-inflammatory diketopiperazine alkaloids from the marine-derived fungus Penicillium brasilianum

Diketopiperazine alkaloids have proven the most abundant heterocyclic alkaloids up to now, which usually process diverse scaffolds and rich biological activities. In our search for bioactive diketopiperazine alkaloids from marine-derived fungi, two novel diketopiperazine alkaloids, penipiperazine A (1) and its biogenetically related new metabolite (2), together with a known analogue neofipiperzine C (3), were obtained from the strain Penicillium brasilianum. Their planar structures and absolute configurations were elucidated by extensive spectroscopic analyses, 13C NMR calculation, Marfey’s, ECD, and ORD methods. Compound 1 featured a unique 6/5/6/6/5 indole-pyrazino-pyrazino-pyrrolo system, and its plausible biogenetic pathway was also proposed. Additionally, compounds 1–3 have been tested for their inflammatory activities. 1 and 2 significantly inhibited the release of NO and the expression of related pro-inflammatory cytokines on LPS-stimulated RAW264.7 cells, suggesting they could be attracting candidate for further development as anti-inflammatory agent.Key points• A novel diketopiperazine alkaloid featuring a unique 6/5/6/6/5 indole-pyrazino-pyrazino-pyrrolo system was isolated from the marine fungus Penicillium brasilianum.• The structure of 1 was elucidated by detailed analysis of 2D NMR data, 13C NMR calculation, Marfey’s, ECD, and ORD methods.• Compounds 1 and 2 significantly inhibited the release of NO and the expression of related pro-inflammatory cytokines on LPS-stimulated RAW264.7 cells.Graphical

Chemical Epigenetic Regulation Secondary Metabolites Derived from Aspergillus sydowii DL1045 with Inhibitory Activities for Protein Tyrosine Phosphatases.

Protein tyrosine phosphatases (PTPs) are ubiquitous in living organisms and are promising drug targets for cancer, diabetes/obesity, and autoimmune disorders. In this study, a histone deacetylase inhibitor called suberoylanilide hydroxamic acid (SAHA) was added to a culture of marine fungi (Aspergillus sydowii DL1045) to identify potential drug candidates related to PTP inhibition. Then, the profile of the induced metabolites was characterized using an integrated metabolomics strategy. In total, 46% of the total SMs were regulated secondary metabolites (SMs), among which 20 newly biosynthesized metabolites (10% of the total SMs) were identified only in chemical epigenetic regulation (CER) broth. One was identified as a novel compound, and fourteen compounds were identified from Aspergillus sydowii first. SAHA derivatives were also biotransformed by A. sydowii DL1045, and five of these derivatives were identified. Based on the bioassay, some of the newly synthesized metabolites exhibited inhibitory effects on PTPs. The novel compound sydowimide A (A11) inhibited Src homology region 2 domain-containing phosphatase-1 (SHP1), T-cell protein tyrosine phosphatase (TCPTP) and leukocyte common antigen (CD45), with IC50 values of 1.5, 2.4 and 18.83 μM, respectively. Diorcinol (A3) displayed the strongest inhibitory effect on SHP1, with an IC50 value of 0.96 μM. The structure-activity relationship analysis and docking studies of A3 analogs indicated that the substitution of the carboxyl group reduced the activity of A3. Research has demonstrated that CER positively impacts changes in the secondary metabolic patterns of A. sydowii DL1045. The compounds produced through this approach will provide valuable insights for the creation and advancement of novel drug candidates related to PTP inhibition.

Cytotoxic Compounds from Marine Fungi: Sources, Structures, and Bioactivity.

Marine fungi, such as species from the Penicillium and Aspergillus genera, are prolific producers of a diversity of natural products with cytotoxic properties. These fungi have been successfully isolated and identified from various marine sources, including sponges, coral, algae, mangroves, sediment, and seawater. The cytotoxic compounds derived from marine fungi can be categorized into five distinct classes: polyketides, peptides, terpenoids and sterols, hybrids, and other miscellaneous compounds. Notably, the pre-eminent group among these compounds comprises polyketides, accounting for 307 out of 642 identified compounds. Particularly, within this collection, 23 out of the 642 compounds exhibit remarkable cytotoxic potency, with IC50 values measured at the nanomolar (nM) or nanogram per milliliter (ng/mL) levels. This review elucidates the originating fungal strains, the sources of isolation, chemical structures, and the noteworthy antitumor activity of the 642 novel natural products isolated from marine fungi. The scope of this review encompasses the period from 1991 to 2023.