Endophytic Fungus Xylaria Research Articles

The Cytochalasins and Polyketides from a Mangrove Endophytic Fungus Xylaria arbuscula QYF.

Twelve compounds, including four undescribed cytochalasins, xylariachalasins A-D (1-4), four undescribed polyketides (5-8), and four known cytochalasins (9-12), were isolated from the mangrove endophytic fungus Xylaria arbuscula QYF. Their structures and absolute configurations were established by extensive spectroscopic analyses (1D and 2D NMR, HRESIMS), electronic circular dichroism (ECD) calculations, 13C NMR calculation and DP4+ analysis, single-crystal X-ray diffraction, and the modified Mosher ester method. Compounds 1 and 2 are rare cytochalasin hydroperoxides. In bioactivity assays, Compound 2 exhibited moderate antimicrobial activities against Staphylococcus aureus and Candida albicans with MIC values of 12.5 μM for both Compound 10 exhibited significant cytotoxic activity against MDA-MB-435 with an IC50 value of 3.61 ± 1.60 μM.

Xylatolides A and B, new 10-membered macrolides from the endophytic fungus Xylaria sp.

Chemical investigation of the fungal endophyte Xylaria sp. isolated from leaves of Moringa oleifera, collected in Cameroon, resulted in the previously undescribed 10-membered macrolide, and two known naturalproducts. The structures of the xylatolides A and B were unambiguously identified by their mass spectra and by extensive 1D and 2D NMR spectroscopic analysis, featuring a 10-membered lactone core structure with oxygenated substituents and an unsubstituted 10-alkyl chain presenting seven carbon atoms. Compounds were screened for their cytotoxic potential against the human HepG2 hepatocellular carcinoma cells and HCT-116 cells (human colon carcinoma cell line). Moreover, the isolated compounds were also assayed against a small panel ofsensitive strains including the bacterial species Escherichia coli, Staphylococcus aureus, and Mycobacterium tuberculosis as well as against the fungal species Candida albicans. However, no significant activities were found.

New Pyranone Derivatives and Sesquiterpenoid Isolated from the Endophytic Fungus Xylaria sp. Z184.

The fungus Xylaria sp. Z184, harvested from the leaves of Fallopia convolvulus (L.) Á. Löve, has been isolated for the first time. Chemical investigation on the methanol extract of the culture broth of the titles strain led to the discovery of three new pyranone derivatives, called fallopiaxylaresters A-C (1-3), and a new bisabolane-type sesquiterpenoid, named fallopiaxylarol A (4), along with the first complete set of spectroscopic data for the previously reported pestalotiopyrone M (5). Known pyranone derivatives (6-11), sesquiterpenoids (12-14), isocoumarin derivatives (15-17), and an aromatic allenic ether (18) were also co-isolated in this study. All new structures were elucidated by the interpretation of HRESIMS, 1D, 2D NMR spectroscopy, and quantum chemical computation approach. The in vitro antimicrobial, anti-inflammatory, and α-glucosidase-inhibitory activities of the selected compounds and the crude extract were evaluated. The extract was shown to inhibit nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells, with an inhibition rate of 77.28 ± 0.82% at a concentration of 50 μg/mL. The compounds 5, 7, and 8 displayed weak antibacterial activity against Staphylococcus areus subsp. aureus at a concentration of 100 μM.

Secondary Metabolites from the Endophytic Fungus Xylaria sp. GDG-102 by Osmac Strategy and Their Antibacterial Activities

Secondary Metabolites from the Endophytic Fungus Xylaria sp. GDG-102 by Osmac Strategy and Their Antibacterial Activities

Xylarcurcosides A-C, three novel isopimarane-type diterpene glycosides from Xylaria curta YSJ-5

Three previously undescribed isopimarane-type diterpene glycosides named as xylarcurcosides A-C (1–3) along with two known ones 16-α-d-mannopyranosyloxyisopimar-7-en-19-oic acid (4) and hypoxylonoid A (5) were successfully isolated from an ethyl acetate extract of the endophytic fungus Xylaria curta YSJ-5 growing in leaves of Alpinia zerumbet. The spectroscopic methods, electronic circular dichroism (ECD) calculations, and X-ray diffraction experiments were conducted to identify their absolute chemical structures. All these compounds were tested for in vitro cytotoxic, anti-inflammatory, α-glucosidase inhibitory, and antibacterial activities. As a result, these novel compounds demonstrated no obvious cytotoxic and antibacterial activity.

A novel biologically active xylaphenoside from the endophytic fungus Xylaria CGMCC No.5410.

A novel 3,4-dihydroisocoumarin glycoside (1) was obtained from the culture of endophytic fungal Xylaria CGMCC No.5410 from the leaves of Selaginella moellendorffii Hieron, together with five known compounds (2-6). Their structures elucidations were conducted by HRESIMS, NMR and IR spectroscopic analysis. All the isolated compounds were evaluated for their antimicrobial, anti-tumor, and anti-HIV-1 activities. Compound 1 only displayed weak antimicrobial activity against micrococcus luteus. The other known compounds showed different antimicrobial, anti-tumor, or anti-HIV-1 activities.

Six Unprecedented Cytochalasin Derivatives from the Potato Endophytic Fungus Xylaria curta E10 and Their Cytotoxicity.

Six previously undescribed cytochalasins, Curtachalasins X1-X6 (1-6), together with six known compounds (7-12) were isolated from the endophytic fungus Xylaria curta E10 harbored in the plant Solanum tuberosum. The structures were elucidated by the interpretation of HRESIMS, UV, and NMR data. The absolute configurations of Curtachalasins X1-X6 were determined by comparison of their experimental and calculated electronic circular dichroism (ECD) spectra. In bioassays, Curtachalasin X1 (1) and X5 (5) showed cytotoxic activity against the MCF-7 cell line with IC50 values of 2.03 μM and 0.85 μM, respectively.

Secondary Metabolites from the Endophytic Fungus Xylaria grammica and Their Anti-Inflammatory Activities

Secondary Metabolites from the Endophytic Fungus Xylaria grammica and Their Anti-Inflammatory Activities

Two new cytochalasins from the endophytic fungus Xylaria sp. GDGJ-77B

Two new open-chain cytochalasins, xylarchalasins A and B (1 and 2), together with six known analogues (3-8), were isolated from the endophytic fungus Xylaria sp. GDGJ-77B from the Chinese medicinal plant Sophora tonkinensis. Their structures were elucidated on the basis of comprehensive spectroscopic analysis. Compound 2 displayed moderate antibacterial activities against Bacillus subtilis and Escherichia coli with MIC values of 25 and 12.5 μg/mL, respectively.

Elucidation of the nematicidal mode of action of grammicin on Caenorhabditis elegans

Grammicin (Gra) is derived from the endophytic fungus Xylaria grammica EL000614 and shows nematicidal activity against the devastating root-knot nematode Meloidogyne incognita in-vitro, in planta, and in-field experiments. However, the mechanism of the nematicidal action of Gra remains unclear. In this study, Gra exposure to the model genetic organism Caenorhabditis elegans affected its L1, L2/3, L4, and young adult stages. In addition, Gra treatment increased the intracellular reactive oxygen species (ROS) levels of C. elegans and M. incognita. Molecular docking interaction analysis indicated that Gra could bind and interact with GCS-1, GST-4, and DAF-16a in order of low binding energy, followed by SOD-3, SKN-1, and DAF-16b. This implies that the anthelmintic action of Gra is related to the oxidative stress response. To validate this mechanism, we examined the expression of the genes involved in the oxidative stress responses following treatment with Gra using transgenic C. elegans strains such as the TJ356 strain zIs356 [daf-16p::daf-16a/b::GFP + rol-6 (su1006)], LD1 ldIs7 [skn-1p::skn-1b/c::GFP + rol-6 (su1006)], LD1171 ldIs3 [gcs-1p::GFP + rol-6 (su1006)], CL2166 dvIs19 [(pAF15) gst-4p::GFP::NLS], and CF1553 strain muIs84 [(pAD76) sod-3p::GFP + rol-6 (su1006)]. Gra treatment caused nuclear translocation of DAF-16/FoxO and enhanced gst-4::GFP expression, but it had no change in sod-3::GFP expression. These results indicate that Gra induces oxidative stress response via phase II detoxification without reduced cellular redox machinery. Gra treatment also inhibited the nuclear localization of SKN-1::GFP in the intestine, which may lead to a condition in which oxidative stress tolerance is insufficient to protect C. elegans by the inactivation of SKN-1, thus inducing nematode lethality. Furthermore, Gra caused the mortality of two mutant strains of C. elegans, CB113 and DA1316, which are resistant to aldicarb and ivermectin, respectively. This indicates that the mode of action of Gra is different from the traditional nematicides currently in use, suggesting that it could help develop novel approaches to control plant-parasitic nematodes.

Paecilins F-P, new dimeric chromanones isolated from the endophytic fungus Xylaria curta E10, and structural revision of paecilin A.

A total of eleven new dimeric chromanones, paecilins F-P (2–12), were isolated from the endophytic fungus Xylaria curta E10, along with four known analogs (1, 13–15). Their structures and absolute configurations were determined by extensive experimental spectroscopic methods, single-crystal X-ray diffraction, and equivalent circulating density (ECD) calculations. In addition, the structure of paecilin A, which was reported to be a symmetric C8-C8′ dimeric pattern, was revised by analysis of the nuclear magnetic resonance (NMR) data, and single-crystal X-ray diffraction. Compound 1 showed antifungal activity against the human pathogenic fungus Candida albicans with a minimum inhibitory concentration of 16 μg/mL, and Compounds 8 and 10 showed antibacterial activity against the gram-negative bacterium Escherichia coli with the same minimum inhibitory concentration of 16 μg/mL.

Biotization of highbush blueberry with ericoid mycorrhizal and endophytic fungi improves plant growth and vitality.

Ecological methods are becoming increasingly popular. One of these methods is plant biotization. In our paper, we focus on selection of Vaccinium corymbosum hairy root-inhabiting fungi for plant growth promotion in a single microorganism inoculation setup and then composed a multiorganismal inoculum enriched with a representative of another group of fungi, leaf endophytes. The hairy roots of V. corymbosum hosted 13 fungal taxa. In single inoculation of the plant with fungal strains, the most beneficial for plant growth were Oidiodendron maius and Phialocephala fortinii. Additional inoculation of the plants with three root symbiotic fungi (O. maius, Hymenoscyphus sp. and P. fortinii) and with the endophytic fungus Xylaria sp. increased plant height in laboratory experiments. On a semi-industrial scale, inoculation improved plant biomass and vitality. Therefore, the amendment of root-associated fungal communities with a mixture of ericoid mycorrhizal and endophytic fungi may represent an alternative to conventional fertilization and pesticide application in large-scale blueberry production. KEY POINTS: • O. maius and P. fortinii significantly stimulated V. corymbosum growth in a single inoculation. • Multimicroorganismal inoculum increased plant biomass and vitality. • Blueberry biotization with ericoid and endophytic fungi is recommended.

Polyhydroxylated sesquiterpenes and ergostane glycosides produced by the endophytic fungus Xylaria sp. from Azadirachta indica

The investigation of the metabolites from the endophytic fungus Xylaria sp. YM 311647 in solid fermentation resulted in the isolation of six undescribed compounds, namely xylarioxides A–F, respectively. These included one eremophilane sesquiterpene, three guaiane sesquiterpene glycosides, and two ergostane glycosides. The structures of the compounds were determined by extensive analyses of spectroscopic data, including 1D and 2D NMR, as well as HRESIMS data. The stereochemistry of xylarioxide A was confirmed by X-ray crystallographic analysis. All of the isolated compounds were assayed for their antifungal activities against seven phytopathogenic fungi and two human pathogenic fungi. Among them, xylarioxides A, E and F showed potent activities against the tested phytopathogens. Particularly, xylarioxide E exhibited the highest activity against Gibberella saubinetii, Curvularia lunata, and Colletotrichum gloeosporioides with MIC values of 4, 4, and 8 μg/mL, respectively, which were comparable to the positive control of nystatin. Interestingly, guaiane sesquiterpene glycosides have been rarely reported from fungal sources. Additionally, xylarioxide E represented an unusual naturally occurring 3,4-seco-steroidal glycoside with a seven-membered lactone in ring A.

Rare cytochalasans isolated from the mangrove endophytic fungus Xylaria arbuscula

Four new cytochalasans, arbuschalasins A–D (1–4), along with thirteen known analogues (5–17), were isolated from the solid rice medium of endophytic fungus Xylaria arbuscula. Arbuschalasins A–B feature a rare 5/6/6/6 fused ring system while arbuschalasin D was characterized as the first example of natural cytochalasans that possesses a 5/5/11 fused scaffold. The structures of 1–4 were assigned by spectroscopic data, with their absolute structures being determined by electronic circular dichroism (ECD) calculations. All of the isolates were evaluated against the human colorectal adenocarcinoma cell lines (HCT15). Compounds 6 and 7 showed significant inhibitory effects (IC50 values were 13.5 and 13.4 μM, respectively), being more active than those of the positive control, fluorouracil (103.1 μM).

Bioactive specialised metabolites from the endophytic fungus Xylaria sp. of Cudrania tricuspidata

Fourteen undescribed compounds, including five 2,5-diarylcyclopentenones xylariaones A1−B2, seven α-pyrone derivatives xylaripyones A−G, one γ-pyrone derivative xylaripyone H, one diketopiperazine cyclo-(L-Leu-N-ethyl-L-Glu), and two known diketopiperazines, were isolated from cultures of the endophytic fungus Xylaria sp., which was separated from Cudrania tricuspidata Bureau ex Lavallée. Their structures were determined by analysing extensive spectroscopic data (HRESIMS and NMR) and electronic circular dichroism (ECD) calculations. Furthermore, these compounds were evaluated for potential antiproliferative activity against the human tumour cell lines PC3 and A549, and the results showed that xylaripyone D exhibited moderate inhibitory activity against the proliferation of PC3 cell lines with an IC50 value of 14.75 μM. Meanwhile, xylariaone A3 and xylaripyone F displayed weak inhibitory effects on NO production in RAW 264.7 murine macrophages with IC50 values of 49.76 and 69.68 μM, respectively.

Bioactive PKS-NRPS Alkaloids from the Plant-Derived Endophytic Fungus Xylaria arbuscula.

A novel hybrid PKS–NRPS alkaloid, xylarialoid A (1), containing a 13-membered macrocyclic moiety and [5,5,6] fused tricarbocyclic rings, together with ten known cytochalasins (2–11), was isolated from a plant-derived endophytic fungus, Xylaria arbuscula. The chemical structures of all compounds were elucidated using 1D and 2D NMR, HR ESIMS spectroscopic analyses, and electronic circular dichroism (ECD) calculation. Compounds 1–3 and 10 exhibited significant antitumor activities against A549 and Hep G2 cell lines, with IC50 values of 3.6–19.6 μM. In addition, compound 1 showed potent anti-inflammatory activity against LPS-induced nitric oxide (NO) production in macrophage RAW 264.7 cells (IC50, 6.6 μM).

Antibacterial Screening of Endophytic Fungus Xylaria sp. derived from Andrographis paniculata (Sambiloto)

AIM: The purpose of this research is to evaluate the antibacterial activity of endophytic fungi derived from the flowers of Andrographis paniculata (Sambiloto). METHODS: The endophytic fungi were obtained following the dilution method with potato dextrose agar as media. Four isolates of fungi have been obtained and then fermented with rice media for 3 weeks. The fermented fungi were extracted with ethyl acetate (EtOAc) and evaporated to yield the EtOAc extract. All EtOAc extracts were evaluated for their antibacterial activity using agar diffusion method. RESULTS: The results indicated that the EtOAc extract from fungus RG-2 was the potential source of antibacterial compounds. Molecular identification showing fungus RG-2 was Xylaria sp. CONCLUSION: Further investigation of the antibacterial compounds produced by fungus Xylaria sp. derived from the flowers of A. paniculata will be performed in the future. To the best of our knowledge, endophytic fungal Xylaria sp. is firstly isolated from A. paniculata.

New cytochalasans from an endophytic Xylaria species associated with Costa Rican Palicourea elata (Rubiaceae)

Four new leucine-derived cytochalasans, possessing a 5,6,5,8-ring (1) and a 5,6,11-ring core (2–4), were isolated from a cultivated endophytic fungus Xylaria sp. strain WH2D4 (Xylariaceae). This fungus was isolated from leaves of the neotropical tree species Palicourea elata (Sw.) Borhidi (Rubiaceae) collected in Costa Rica. The chemical structures were determined by employing IR, MS as well as 1D- and 2D-NMR experiments. The stereochemistry at C-15 of compound 4 was determined by quantum calculations. The isolated compounds did not affect germination and growth of Trichoderma reesei and the opportunistic human fungal pathogen T. longibrachiatum.

Induction of metabolic variability of the endophytic fungus Xylaria sp. by OSMAC approach and experimental design.

This work has as the main focus, to analyze the behavior of physic-chemical variations from the fungus Xylaria sp., through the OSMAC (One Strain, Many Compounds) approach as an efficient way of obtaining new compounds. To perform such inductions and to explore the variability of the metabolic network of this microorganism, a factorial design was designed to induce variability (or enhancement) of metabolites. In view of chemometric insights, the planned inductions were imposed on the microorganism and variations in the chemical profile were observed in the crude extracts. Through mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance-based profiles, combined with multivariate analysis through Principal Component Analysis (PCA), it was observed a marked variability of signals, confirming the efficacy in the metabolic alteration, defining the culture medium and agitation as the most important variables in the metabolic variability of the fungus. However, the extract mass is more significant for the agitation variable, and there is no relationship between the mass of crude extract and the amount of molecular signals of the complex matrices studied.

A New Chromone Derivative from Endophytic Fungus Xylaria sp. ECN212

A New Chromone Derivative from Endophytic Fungus Xylaria sp. ECN212