Endophytic Fungus Aspergillus Sp Research Articles

Bio-fabricated zinc oxide nanoparticles mediated by endophytic fungus Aspergillus sp. SA17 with antimicrobial and anticancer activities: in vitro supported by in silico studies.

In recent years, the world's attention has been drawn to antimicrobial resistance (AMR) because to the frightening prospect of growing death rates. Nanomaterials are being investigated due to their potential in a wide range of technical and biological applications. The purpose of this study was to biosynthesis zinc oxide nanoparticles (ZnONPs) using Aspergillus sp. SA17 fungal extract, followed by characterization of the produced nanoparticles (NP) using electron microscopy (TEM and SEM), UV-analysis, X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FT-IR). The HR-TEM revealed spherical nanoparticles with an average size of 7.2 nm, and XRD validated the crystalline nature and crystal structure features of the generated ZnONPs, while the zeta potential was 18.16 mV, indicating that the particles' surfaces are positively charged. The FT-IR was also used to identify the biomolecules involved in the synthesis of ZnONPs. The antibacterial and anticancer properties of both the crude fungal extract and its nano-form against several microbial strains and cancer cell lines were also investigated. Inhibition zone diameters against pathogenic bacteria ranged from 3 to 13 mm, while IC50 values against cancer cell lines ranged from 17.65 to 84.55 M. Additionally, 33 compounds, including flavonoids, phenolic acids, coumarins, organic acids, anthraquinones, and lignans, were discovered through chemical profiling of the extract using UPLC-QTOF-MS/MS. Some molecules, such pomiferin and glabrol, may be useful for antibacterial purposes, according to in silico study, while daidzein 4'-sulfate showed promise as an anti-cancer metabolite.

Optimization of fungicidal and acaricidal metabolite production by endophytic fungus Aspergillus sp. SPH2

The endophytic fungus Aspergillus sp. SPH2 was isolated from the stems of the endemic plant Bethencourtia palmensis and its extracts were found to have strong fungicidal effects against Botrytis cinerea and ixodicidal effects against Hyalomma lusitanicum at different fermentation times. In this study, the fungus was grown using three different culture media and two methodologies, Microparticulate Enhancement Cultivation (MPEC) and Semi-Solid-State Fermentation (Semi-SSF), to increase the production of secondary metabolites during submerged fermentation. The addition of an inert support to the culture medium (Semi-SSF) resulted in a significant increase in the extract production. However, when talcum powder was added to different culture media, unexpected results were observed, with a decrease in the production of the biocompounds of interest. Metabolomic analyses showed that the production of aspergillic, neoaspergillic, and neohydroxyaspergillic acids peaked in the first few days of fermentation, with notable differences observed among the methodologies and culture media. Mellein production was particularly affected by the addition of an inert support to the culture medium. These results highlight the importance of surface properties and morphology of spores and mycelia during fermentation by this fungal species.Graphical

Induction of antimicrobial, antioxidant metabolites production by co-cultivation of two red-sea-sponge-associated Aspergillus sp. CO2 and Bacillus sp. COBZ21

The growing spread of infectious diseases has become a potential global health threat to human beings. According to WHO reports, in this study, we investigated the impact of co-cultivating the isolated endophytic fungus Aspergillus sp. CO2 and Bacillus sp. COBZ21 as a method to stimulate the production of natural bioactive substances. (GC/MS)-based metabolomics profiling of two sponge-associated microbes, Aspergillus sp. CO2 and Bacillus sp. COBZ21, revealed that the co-culture of these two isolates induced the accumulation of metabolites that were not traced in their axenic cultures. By detection of different activities of extracts of Bacillus sp. COBZ21 and Aspergillus sp. CO2 and coculture between Bacillus sp. COBZ21 and Aspergillus sp. CO2. It was noted that the coculture strategy was the reason for a notable increase in some different activities, such as the antimicrobial activity, which showed potent activity against Escherichia coli ATCC 25,922, Staphylococcus aureus NRRLB-767, and Candida albicans ATCC 10,231. The antibiofilm activity showed significant biofilm inhibitory activity toward Bacillus subtilis ATCC 6633, Pseudomonas aeruginosa ATCC 10,145, and Staph aureus NRRLB-767, with activity up to 53.66, 71.17, and 47.89%, while it showed low activity against E. coli ATCC 25,922, while the antioxidant activity based on the DPPH assay showed maximum activity (75.25%). GC-MS investigations revealed the presence of variable chemical constituents belonging to different chemical categories, which reflected their chemical diversity. The main components are (+-) cis-Deethylburnamine (2.66%), Bis(3,6,9,12-tetraoxapentaethylene) crowno-N,N,N’,N’-tetra methylpphanediamine (2.48%), and 11-phenyl-2,4,6,8-tetra(2-thienyl)-11-aza-5,13-dithiaeteracyclo[7.3.0.1(2,8)0.0(3,7)] trideca-3,6-diene-10,12,13-trione (3.13%), respectively, for Bacillus sp. axenic culture, Aspergillus sp. CO2, Aspergillus sp. CO2, and Bacillus sp. COBZ21 coculture. By studying the ADME-related physicochemical properties of coculture extract, the compound showed log Po/w values above 5 (8.82). The solubility of the substance was moderate. In order to provide a comprehensive definition of medicinal chemistry and leadlikness, it is important to note that the latter did not meet the criteria outlined in the rule of three (RO3). The toxicity prediction of the coculture extract was performed using the ProTox II web server, which showed that the selected compound has no pronounced toxicity.

Diisoprenyl-cyclohexene-type meroterpenoids from a mangrove endophytic fungus Aspergillus sp. GXNU-Y65 and their anti-nonalcoholic steatohepatitis activity in AML12 cells

Nine previously undescribed diisoprenyl-cyclohexene-type meroterpenoids, aspergienynes A-I, together with five known analogues, were obtained from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y65. The diisoprenyl-cyclohexene-type meroterpenoids were elucidated based on multispectroscopic analysis, and the previously undescribed compounds’ absolute configurations were established via electronic circular dichroism calculations. Biological activity results indicated that aspergienyne C (compound 3) had strong anti-nonalcoholic steatohepatitis activity against AML12 cells treated with PA (Palmitic acid) + OA (Oleic acid). At the same concentration of 20 μM, 3 significantly reduced triglyceride (TG) content compared with fenofibrate (positive control) in PA + OA treated AML12 cells, and obviously increased phosphorylation of acetyl-CoA carboxylase.

A new sulphur-containing metabolite from a mangrove endophytic fungus Aspergillus sp. GXNU-MA

A new sulphur-containing metabolite, asperiguxidione A (1), was isolated from a mangrove endophytic fungus Aspergillus sp. GXNU-MA, and four known alkaloids 2-5, were isolated together from this strain. Their structures were determined by the com­bination of 1D and 2D NMR spectroscopy, HR-ESI-MS, and ECD analysis. Compounds 1 and 2 exhibited mediate activity against Staphylococcus aureus and Enterobacter aerogenes with equal MIC values of 12.5 μg/mL. Compound 3 reduced NO production in LPS-stimulated cells with an IC50 value of 13.329 ± 0.53 μg/mL in the anti-inflammatory assay.

Rhizoaspergillin A and Rhizoaspergillinol A, including a Unique Orsellinic Acid-Ribose-Pyridazinone-N-Oxide Hybrid, from the Mangrove Endophytic Fungus Aspergillus sp. A1E3.

Two new compounds, named rhizoaspergillin A (1) and rhizoaspergillinol A (2), were isolated from the mangrove endophytic fungus Aspergillus sp. A1E3, associated with the fruit of Rhizophora mucronata, together with averufanin (3). The planar structures and absolute configurations of rhizoaspergillinol A (2) and averufanin (3) were established by extensive NMR investigations and quantum-chemical electronic circular dichroism (ECD) calculations. Most notably, the constitution and absolute configuration of rhizoaspergillin A (1) were unambiguously determined by single-crystal X-ray diffraction analysis of its tri-pivaloyl derivative 4, conducted with Cu Kα radiation, whereas those of averufanin (3) were first clarified by quantum-chemical ECD calculations. Rhizoaspergillin A is the first orsellinic acid-ribose-pyridazinone-N-oxide hybrid containing a unique β-oxo-2,3-dihydropyridazine 1-oxide moiety, whereas rhizoaspergillinol A (2) and averufanin (3) are sterigmatocystin and anthraquinone derivatives, respectively. From the perspective of biosynthesis, rhizoaspergillin A (1) could be originated from the combined assembly of three building blocks, viz., orsellinic acid, β-D-ribofuranose, and L-glutamine. It is an unprecedented alkaloid-N-oxide involving biosynthetic pathways of polyketides, pentose, and amino acids. In addition, rhizoaspergillinol A (2) exhibited potent antiproliferative activity against four cancer cell lines. It could dose-dependently induce G2/M phase arrest in HepG2 cells.

Asperinamide A, an anti-inflammatory prenylated indole alkaloid possessing an unprecedented bicyclo[2.2.2]diazaoctane fused with substituted piperidine scaffold from Aspergillus sp. TE-65L

Prenylated indole alkaloids (PIAs) containing a bicyclo[2.2.2]diazaoctane ring have gained extensive attention due to their chemical (especially stereochemical), biosynthetic/synthetic, and bioactive interests. In the present study, An unprecedented PIA (namely asperinamide A, 1), featuring a 6/6/5/6/6/6/5 heptacyclic scaffold fused with bicyclo[2.2.2]diazaoctane and substituted piperidine, hitherto unknown among this family of PIAs, along with its biosynthetic-related analogues sclerotiamide (2) and (+)-stephacidin A (3), were isolated from the Nicotiana tabacum-derived endophytic fungus Aspergillus sp. TE-65L. Their structures were unambiguously determined by detailed NMR, mass spectra, and X-ray crystallographic analysis. A detailed plausible biosynthetic analysis for compounds 1–3 was proposed, which revealed that the unique substituted piperidine ring may be formed through a radical-mediated rearrangement. Compound 1 showed significant anti-inflammatory activity targeting the TLR4-MD2 site in the TLR4/NF-κB signaling pathway.

Isolation and insecticidal activities of new cyclic peptides from mangrove endophytic fungus Aspergillus sp. GXNU-4QQY1a

An investigation on bioactive metabolites from the mangrove endophytic fungus Aspergillus sp. GXNU-4QQY1a led to the isolation of two undescribed cyclic peptides, guaspertide A (1) and guaspertide B (2), together with six known compounds, 3–8. These structures and the new compounds' absolute configuration were determined by mass spectrometry analysis, nuclear magnetic resonance spectrum, electronic circular dichroism, and single-crystal X-ray diffraction. Insecticidal assays were carried out with compounds 1–8, and the results showed that compounds 1–3 and 8 exhibited good insecticidal activity against citrus psyllids.

A new chromone from Kandelia candel endophytic fungus Aspergillus sp. ZJ-68

One chromone (1), together with four known alkaloids, were isolated from the mangrove endophytic fungus Aspergillus sp. ZJ-68. Their structures were elucidated by a combination of HRESIMS and NMR spectroscopic analyses. Compound 1 showed strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 4.094 ± 0.8 μM, which was better than positive drug indomethacin (IC50=35.8 ± 0.5 μM).

Cytochalasans from the Endophytic Fungus Aspergillus sp. LE2: Their Structures, Antibacterial and NO Production Inhibitory Activities

Six new cytochalasans-namely, aspergicytochalasins A-F (1-6)-together with five known analogs were isolated and characterized from the endophytic fungus Aspergillus sp. from the medicinal plant Lonicera japonica. The structures of the new compounds were established by NMR and MS methods as well as single crystal X-ray diffractions. Compounds 3 and 4 showed weak antibacterial activities to Staphylococcus aureus, with MIC values of 128 and 64 μg/mL, respectively. Compounds 1, 3, 5 and 6 showed inhibitory activities on NO production, with IC50 values less than 40 μM.

Two new alkaloids from a strain of endophytic fungus Aspergillus sp.

19-Hydroxybrevianamide M (1) and 6 R-methoxybrevianamide V (2), two new alkaloids, were isolated from an extract of the endophytic fungus Aspergillus sp. JNU18HC0517J, together with six known analogues (3– 8). Their structures were elucidated by extensive spectroscopic analyses, NMR calculations, and ECD calculations. 6 R-methoxybrevianamide V (2) was the first L-proline indole DKP alkaloid with substitution at C-6 on the proline ring. Furthermore, the cytotoxities and antimicrobial activities of these isolated compounds were also evaluated. Compound 8 exhibited moderate antibacterial activity against Staphylococcus aureus 209 P with a minimal inhibitory concentration (MIC) value of 16 µg/ml.

Asperphenyltones A and B: New Phenylfuropyridinone Skeleton from an Endophytic Aspergillus sp. GXNU-A1

Chemical investigation of the fermentation extract of the mangrove endophytic fungus Aspergillus sp. GXNU-A1, isolated from Acanthus ilicifolius L., discovered an undescribed pair of enantiomers (asperphenyltones A and B (±1)), together with four previously described metabolites: nodulisporol (2), isosclerone (3), 2,3,4-trihydroxy-6-(hydroxymethyl)-5-methylbenzyl alcohol (4), and 4,6-dihydroxy-5-methoxy-7-methyl-1,3-dihydroisobenzofuran (5). Analyses of the 1D and 2D NMR spectroscopic data of the compounds supported their structural assignments. The presence of the asperphenyltones A and B, which are a pair of enantiomers, was established by HR-ESI-MS, 1D and 2D NMR data and confirmed by single-crystal X-ray diffraction analysis. Metabolites 1-5 were evaluated for their anti-inflammatory effects on the production of nitric oxide (NO), and 1, 3, and 4 showed significant potential inhibitory activities against NO production in activated macrophages with IC50 values of 26-40 μM, respectively.

An anti-influenza A virus microbial metabolite acts by degrading viral endonuclease PA

The emergence of new highly pathogenic and drug-resistant influenza strains urges the development of novel therapeutics for influenza A virus (IAV). Here, we report the discovery of an anti-IAV microbial metabolite called APL-16-5 that was originally isolated from the plant endophytic fungus Aspergillus sp. CPCC 400735. APL-16-5 binds to both the E3 ligase TRIM25 and IAV polymerase subunit PA, leading to TRIM25 ubiquitination of PA and subsequent degradation of PA in the proteasome. This mode of action conforms to that of a proteolysis targeting chimera which employs the cellular ubiquitin-proteasome machinery to chemically induce the degradation of target proteins. Importantly, APL-16-5 potently inhibits IAV and protects mice from lethal IAV infection. Therefore, we have identified a natural microbial metabolite with potent in vivo anti-IAV activity and the potential of becoming a new IAV therapeutic. The antiviral mechanism of APL-16-5 opens the possibility of improving its anti-IAV potency and specificity by adjusting its affinity for TRIM25 and viral PA protein through medicinal chemistry.

The Chemical Profiling, Docking Study, and Antimicrobial and Antibiofilm Activities of the Endophytic fungi Aspergillus sp. AP5.

Growing data suggest that Aspergillus niger, an endophytic fungus, is a rich source of natural compounds with a wide range of biological properties. This study aimed to examine the antimicrobial and antibiofilm capabilities of the Phragmites australis-derived endophyte against a set of pathogenic bacteria and fungi. The endophytic fungus Aspergillus sp. AP5 was isolated from the leaves of P. australis. The chemical profile of the fungal crude extract was identified by spectroscopic analysis using LC-HRESIMS. The fungal-derived extract was evaluated for its antimicrobial activity towards a set of pathogenic bacterial and fungal strains including Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris, Klebsiella sp., Candida albicans, and Aspergillus niger. Moreover, antibiofilm activity toward four resistant biofilm-forming bacteria was also evaluated. Additionally, a neural-networking pharmacophore-based visual screening predicted the most probable bioactive compounds in the obtained extract. The AP5-EtOAc extract was found to have potent antibacterial activities against S. aureus, E. coli, and Klebsiella sp., while it exhibited low antibacterial activity toward P. Vulgaris and P. aeruginosa and displayed anticandidal activity. The AP5-EtOAc extract had significant antibiofilm activity in S. aureus, followed by P. aeruginosa. The active metabolites’ antifungal and/or antibacterial activities may be due to targeting the fungal CYP 51 and/or the bacterial Gyr-B.

Polyketide Derivatives, Guhypoxylonols A-D from a Mangrove Endophytic Fungus Aspergillus sp. GXNU-Y45 That Inhibit Nitric Oxide Production.

Four undescribed compounds, guhypoxylonols A (1), B (2), C (3), and D (4), were isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-Y45, together with seven previously reported metabolites. The structures of 1–4 were elucidated based on analysis of HRESIMS and NMR spectroscopic data. The absolute configurations of the stereogenic carbons in 1–3 were established through a combination of spectroscopic data and electronic circular dichroism (ECD). Compounds 1–11 were evaluated for their anti-inflammatory activity. Compounds 1, 3, 4, and 6 showed an inhibitory activity against the production of nitric oxide (NO), with the IC50 values of 14.42 ± 0.11, 18.03 ± 0.14, 16.66 ± 0.21, and 21.05 ± 0.13 μM, respectively.

A new lactone from mangrove endophytic fungus Aspergillus sp. GXNU-A9

A new lactone, asperlactone A (1), and four known lactone derivatives 2–5 were isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-A9. Their structures were elucidated based on high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) datum, extensive nuclear magnetic resonance (NMR) spectroscopic analysis, and comparison with literature data. The structure of 1 was further confirmed by single-crystal X-ray diffraction analysis, and the absolute configuration of 1 was established. Compounds 1–5 were evaluated for their anti-inflammatory activities against nitric oxide (NO) production, and compounds 1–5 showed moderate inhibitory activities with IC50 values ranging from 15.87 to 30.48 µM.

Aspochalasin H1: A New Cyclic Aspochalasin from Hawaiian Plant-Associated Endophytic Fungus Aspergillus sp. FT1307.

Aspergillus is one of the most diverse genera, and it is chemically profound and known to produce many biologically active secondary metabolites. In the present study, a new aspochalasin H1 (1), together with nine known compounds (2–10), were isolated from a Hawaiian plant-associated endophytic fungus Aspergillus sp. FT1307. The structures were elucidated using nuclear magnetic resonance (NMR) (1H, 1H-1H COSY, HSQC, HMBC, ROESY and 1D NOE), high-resolution electrospray ionization mass spectroscopy (HRESIMS), and comparisons with the reported literature. The absolute configuration of the new compound was established by electronic circular dichroism (ECD) in combination with NMR calculations. The new compound contains an epoxide moiety and an adjacent trans-diol, which has not been reported before in the aspochalasin family. The antibacterial screening of the isolated compounds was carried out against pathogenic bacteria (Staphylococcus aureus, Methicillin-resistant S. aureus and Bacillus subtilis). The antiproliferative activity of compounds 1–10 was evaluated against human breast cancer cell lines (MCF-7 and T46D) and ovarian cancer cell lines (A2780).

Optimization of PhysicoChemical Parameters for Production of Cytotoxic Secondary Metabolites and Apoptosis Induction Activities in the Culture Extract of a Marine Algal-Derived Endophytic Fungus Aspergillus sp.

The endophytic fungal community in the marine ecosystem has been demonstrated to be relevant source of novel and pharmacologically active secondary metabolites. The current study focused on the evaluation of cytotoxic and apoptosis induction potential in the culture extracts of endophytic fungi associated with Sargassum muticum, a marine brown alga. The cytotoxicity of the four marine endophytes, Aspergillus sp., Nigrospora sphaerica, Talaromyces purpureogenus, and Talaromyces stipitatus, was evaluated by the MTT assay on HeLa cells. Further, several physicochemical parameters, including growth curve, culture media, and organic solvents, were optimized for enhanced cytotoxic activity of the selected extract. The Aspergillus sp. ethyl acetate extract (ASE) showed maximum cytotoxicity on multiple cancer cell lines. Chemical investigation of the metabolites by gas chromatography–mass spectroscopy (GC-MS) showed the presence of several compounds, including quinoline, indole, 2,4-bis(1,1-dimethylethyl) phenol, and hexadecenoic acid, known to be cytotoxic in ASE. The ASE was then tested for cytotoxicity in vitro on a panel of six human cancer cell lines, namely, HeLa (cervical adenocarcinoma), MCF-7 (breast adenocarcinoma), Hep G2 (hepatocellular carcinoma), A-549 (lung carcinoma), A-431 (skin/epidermis carcinoma), and LN-229 (glioblastoma). HeLa cells were most vulnerable to ASE treatment with an IC50 value of 24 ± 2 μg/ml. The mechanism of cytotoxicity exhibited by the ASE was further investigated on Hela cells. The results showed that the ASE was capable of inducing apoptosis in HeLa cells through production of reactive oxygen species, depolarization of mitochondrial membrane, and activation of the caspase-3 pathway, which shows a possible activation of the intrinsic apoptosis pathway. It also arrested the HeLa cells at the G2/M phase of the cell cycle, eventually leading to apoptosis. Through this study, we add to the knowledge about the marine algae associated with fungal endophytes and report its potential for purifying specific compounds responsible for cytotoxicity.

New immunosuppressive secondary metabolites from the endophytic fungus Aspergillus sp.

Six new metabolites, including two diphenolic derivatives (1 and 2), one pseurotin (3), one butenolide derivative (4), one benzopyran (5) and one isochromane lactone (6), together with ten known compounds (7–16) were isolated from an endophytic fungus Aspergillus sp. Their planar structures and absolute configurations were established based on techniques of MS, NMR, IR, UV, [Rh2(OCOCF3)4] complex-induced ECD, quantum chemical electronic circular dichroism (ECD) calculations, and single crystal X-ray diffraction. Structurally, compound 2 represents the first example of diphenolic derivative possessing an unusual 1-oxaspiro[2.4]heptane core bearing a 5/3 bicyclic skeleton; compound 3 represents the first example of pseurotin type natural products that only one hydroxy group is substituted at side chain. In bioassay, compounds 3, 7 and 8 exhibited potential inhibitory effect on the proliferation of anti-CD3/anti-CD28 monoclonal antibodies (mAbs) induced murine T cells, with IC50 values of (7.81 ± 0.71), (8.25 ± 0.78) and (8.84 ± 0.81) μM, respectively.

Bioactive Indole Diketopiperazine Alkaloids from the Marine Endophytic Fungus Aspergillus sp. YJ191021

Six new prenylated indole diketopiperazine alkaloids, asperthrins A–F (1–6), along with eight known analogues (7–14), were isolated from the marine-derived endophytic fungus Aspergillus sp. YJ191021. Their planar structures and absolute configurations were elucidated by HR-ESI-MS, 1D/2D NMR data, and time-dependent density functional theory (TDDFT)/ECD calculation. The isolated compounds were assayed for their inhibition against three agricultural pathogenic fungi, four fish pathogenic bacteria, and two agricultural pathogenic bacteria. Compound 1 exhibited moderate antifungal and antibacterial activities against Vibrio anguillarum, Xanthomonas oryzae pv. Oryzicola, and Rhizoctonia solani with minimal inhibitory concentration (MIC) values of 8, 12.5, and 25 μg/mL, respectively. Furthermore, 1 displayed notable anti-inflammatory activity with IC50 value of 1.46 ± 0.21 μM in Propionibacterium acnes induced human monocyte cell line (THP-1).