Endophytic Fungus Xylaria Research Articles

An actin depolymerizing agent 19,20-epoxycytochalasin Q of Xylaria sp. BCC 1067 enhanced antifungal action of azole drugs through ROS-mediated cell death in yeast

Multidrug resistance is a highly conserved phenomenon among all living organisms and a major veritable public health problem worldwide. Repetitive uses of antibiotics lead to antimicrobial drug resistance. Here, 19,20-epoxycytochalasin Q (ECQ) was isolated from endophytic fungus Xylaria sp. BCC 1067 and, its chemical structure was determined via chromatographic and spectral methods. ECQ displayed an antifungal activity with low MIC50 of 410 and 55 mg/l in the model yeast Saccharomyces cerevisiae wild-type and ScΔpdr5 strains, respectively. ECQ was a new inducer and potential substrate of key multi-drug efflux pumps S. cerevisiae ScPdr5 and Candida albicans CaCdr1. ECQ targeted actin filament, disrupting actin dynamics of yeast cells. ECQ also sensitized the ScΔsrv2 mutant, lacking suppressor of RasVal19. Overexpression of ScPDR5 or CaCDR1 genes prevented aggregation of actin and alleviated antifungal effect of ECQ. Additionally, ECQ induced high accumulation of reactive oxygen species, caused plasma membrane leakage and decreased yeast cell survival. Importantly, a discovery of ECQ implied a cellular connection between multi-drug resistance and actin stability, an important determinant of transporter mediated-drug resistance mechanism. Combination of ECQ and antifungal azoles displayed promising drug synergy against S. cerevisiae strains expressing multi-drug transporters, thereby providing potential solution for antifungal therapy and chemotherapeutic application.

A New Isocoumarin from the Fungus Xylaria mali

A new isocoumarin, xylariamalirin (1), was isolated from the n-BuOH-soluble fraction of the fermentation broth of an endophytic fungus Xylaria mali, derived from the Taiwanese Lepidagathis stenophyllTaiwana C. B. Clarke ex Hayata (Acanthaceae) growing in the Hengchun Peninsula of southern . The structures were elucidated by spectroscopic analyses, including 1D and 2D NMR experiments, and by HR-ESI-MS mass spectrometry.

Xylarichalasin A, a Halogenated Hexacyclic Cytochalasan from the Fungus Xylaria cf. curta.

A cytochalasan, xylarichalasin A, was obtained from the endophytic fungus Xylaria cf. curta harbored in Solanum tuberosum. Its structure was elucidated by comprehensive spectroscopic methods including HRESIMS, 1D/2D NMR, and residual dipolar coupling analysis as well as quantum chemistry calculations including DFT GIAO 13C NMR and ECD calculation. It has an unprecedented 6/7/5/6/6/6 fused polycyclic structure. In bioassay, xylarichalasin A showed cytotoxicity against human cancer cell lines with IC50 value ranging from 6.3-17.3 μM.

Cytochalasins D1 and C1, unique cytochalasans from endophytic fungus Xylaria cf. curta

Cytochalasins D1 (1) and C1 (2) were isolated from the liquid fermentation of fungus Xylaria cf. curta. Their structures and absolute configurations were determined by comprehensive experimental spectroscopic methods as well as ECD and GIAO 13C NMR calculation. They possess a unique eleven-membered macrocycle with an oxygen bridge. Cytochalasins D1 and C1 showed moderate cytotoxicity against human leukemia cell lines HL-60 with IC50 value of 12.7 and 22.3 μM, respectively.

Cytotoxic 19,20-epoxycytochalasans from endophytic fungus Xylaria cf. curta

Nine new 19,20-epoxycytochalasans (1–9) were isolated from the rice fermentation extracts of endophytic fungus Xylaria cf. curta, along with four known compounds 19,20-epoxycytochalasin C (10), 18-desoxy-19,20-epoxycytochalasin C (11), 19,20-epoxycytochalasin D (12) and 5,6-dihydro-7-oxo-19,20-epoxycytochalasin C (13). Their structures and absolute configurations were determined by 1D and 2D NMR, HRESIMS, X-ray diffraction and ECD calculation. The cytotoxicity of obtained compounds (1−13) was evaluated against human cancer cell lines HL-60, A549, SMMC-7721, MCF-7, and SW480. Remarkably, compound 10 showed significant specific cytotoxicity against HL-60 cell lines with IC50 value of 1.11 μM.

Isolation and enhancement of resveratrol production in Xylaria psidii by exploring the phenomenon of epigenetics: using DNA methyltransferases and histone deacetylase as epigenetic modifiers.

Resveratrol is an important stilbene which is having a high demand due to its therapeutic, cosmeceutical and nutraceutical activities. The current study mainly focuses on strategies to enhance the fungal potential to produce resveratrol via the activation of the cryptic biosynthetic pathway with their particular interest in the antioxidant application. The endophytic fungus Xylaria psidii was isolated from the surface sterilized leaf of Vitis vinifera. With the help of HPLC analysis it is found that resveratrol concentration was maximum and enhanced in case of treatment with 5μm SAHA (52.32μg/mL) and by 10μm AZA (48.94μg/mL) followed by 10μm SAHA (41.10μg/mL) and 5μm AZA (37.72μg/mL). After treatment with different concentration of epigenetic modifiers such as HDAC inhibitors (SAHA) and dMNTs (AZA) inhibitors, a significant increase in antioxidant potential was obtained. In the case of DPPH increase in scavenging potential was found as compared to wild strain. Treatment with 5μm SAHA and by 10μm AZA was showing strong antioxidant potential among all the epigenetic variants as compared to wild strain. In the case of TEAC also the same trend as in the case of DPPH was obtained.

Additional Chemical Constituents of an Endophytic Fungus Xylaria papulis

Additional Chemical Constituents of an Endophytic Fungus Xylaria papulis

Mannosylxylarinolide, a new 3,4-seco-ergostane-type steroidal saponin featuring a β-d-mannose from the endophytic fungus Xylaria sp.

Mannosylxylarinolide (1), a new 3,4-seco-ergostane-type steroidal saponin featuring a β-d-mannose moiety, was isolated from the culture of the endophytic fungus Xylaria sp. that had been isolated from an ornamental plant of Hoya sp. The gross structure was determined by spectroscopic data, and the absolute configuration of the new 3,4-seco-ergostane-type steroidal saponin (1) was determined by X-ray diffraction analysis.

Cytochalasans from the Endophytic Fungus Xylaria cf. curta with Resistance Reversal Activity against Fluconazole-Resistant Candida albicans.

Curtachalasins C-E (1-3), which have an unprecedent bridged 6/6/6/6 ring system, were identified from the endophytic fungus Xylaria cf. curta. Residual dipolar coupling analyses associating with density functional theory calculations were utilized to determine the relative configuration of noncrystallizable compound 2. The absolute configurations of 1-3 were determined by X-ray diffraction and electronic circular dichroism calculations. Remarkably, curtachalasin C (1) showed significant resistance reversal activity against fluconazole-resistant Candida albicans.

Curtachalasins A and B, Two Cytochalasans with a Tetracyclic Skeleton from the Endophytic Fungus Xylaria curta E10.

Two unique cytochalasans, curtachalasins A (1) and B (2), were purified from the endophytic fungus Xylaria curta E10 harbored in the plant Solanum tuberosum. Their structures were determined by extensive spectroscopic methods, X-ray crystallographic analysis, and electronic circular dichroism calculations. These two compounds feature an unprecedented pyrolidine/perhydroanthracene (5/6/6/6 tetracyclic skeleton) fused ring system.

Biotransformation of β-Mangostin by an Endophytic Fungus of Garcinia mangostana to Furnish Xanthenes with an Unprecedented Heterocyclic Skeleton

Biotransformation of β-mangostin (1) by the endophytic fungus Xylaria feejeensis GM06 afforded hexacyclic ring-fused xanthenes with an unprecedented hexacyclic heterocylic skeleton. β-Mangostin (1) was transformed to two diastereomeric pairs of enantiomers, mangostafeejin A [(-)-2a/(+)-2b)] and mangostafeejin B [(-)-3a/(+)-3b)]. The chemical structures of the transformation products were elucidated by analysis of NMR and MS data, and the structure of mangostafeejin A [(-)-2a/(+)-2b)] was confirmed by single-crystal X-ray diffraction analysis. The absolute configurations of 3a and 3b were established on the basis of calculated and measured ECD data using the ECD spectra of 2a and 2b as models. The fungal biotransformation described herein provides an effective method to convert an abundant achiral plant natural product scaffold into new chiral heterocyclic scaffolds representing expanded chemical diversity for biological activity screening.

A new cytochalasin derivative from the mangrove-derived endophytic fungus Xylaria sp. HNWSW-2

A new cytochalasin derivative xylarisin B (1), together with four known compounds astropyrone (2), guaidiol (3), xylaropyrone B (4), and xylaropyrone C (5), were isolated from the fermentation broth of Xylaria sp. HNWSW-2. Their structures were elucidated by spectroscopic data. Among them, compounds 2 and 3 at a concentration of 50 μg/ml showed weak inhibitory activity against AChE with inhibition rates of 10.4 and 12.9%, respectively. In addition, compound 2 also exhibited inhibitory activity against α-glycosidase with inhibition rate of 77.0% at a concentration of 0.25 mg/ml.

Xylarianins A-D from the endophytic fungus Xylaria sp. SYPF 8246 as natural inhibitors of human carboxylesterase 2

Eighteen secondary metabolites were isolated from the fermentation broth of the endophytic fungus Xylaria sp. SYPF 8246, including four new compounds, xylarianins A-D (1–4), three new natural products, 6-methoxycarbonyl-2′-methyl-3,5,4′,6′-tetramethoxy-diphenyl ether (5), 2-chlor-6-methoxycarbonyl-2′-rnethyl-3,5,4′,6′-tetramethoxy-diphenyl ether (6), and 2-chlor-4′-hydroxy-6-methoxy carbonyl-2′-methyl-3,5,6′-trimethoxy-diphenyl ether (7), and eleven known compounds (8–18). Their structural elucidations were conducted by using 1D and 2D NMR, HRESIMS, and Rh2(OCOCF3)4-induced electronic circular dichroism (ECD) spectra analyses. The integrated 1H and 13C NMR data of three new natural products 5–7 were reported for the first time. All the isolated compounds were assayed for their inhibitory activities against human carboxylesterase 2 (hCE 2). Compounds 1, 5–9, and 18 displayed significant inhibitory activities against hCE 2 with IC50 values of 10.43 ± 0.51, 6.69 ± 0.85, 12.36 ± 1.27, 18.25 ± 1.78, 29.78 ± 0.48, 18.86 ± 1.87, and 20.72 ± 1.51 µM, respectively. The interactions between compounds 1 and 5 with hCE 2 were anaylzed by molecular docking.

Eremophilane sesquiterpenes from the endophytic fungus Xylaria sp. GDG-102

A new eremophilane sesquiterpene, xylareremophil (1), together with five known eremophilanes, 1α,10α-epoxy-3α-hydroxyeremophil-7(11)-en-12,8β-olide (2), 1,10α,13-trihydroxyeremophil-7(11)-en-12,8-olide (3), 1α,10α-epoxy-13-hydroxyeremophil-7(11)-en-12,8β-olide (4), mairetolides B (5) and G (6) were isolated from the endophytic fungus Xylaria sp. GDG-102 cultured from Sophora tonkinensis. Their structures were elucidated on the basis of spectroscopic data analysis. The absolute configurations of 1 was determined by comparing computed electronic circular dichroism (ECD) and optical rotation (OR) with experimental results. Compounds 1, 5 and 6 showed antibacterial activities against Proteus vulgaris, Micrococcus luteus, Micrococcus lysodeikticus and Bacillus subtilis with MIC values of 25–100 μg/mL.

Optimization of culture condition, phytoconstituents and cytotoxicity of Xylaria hypoxylon (L.) Grev.

Experiments were carried out to determine the optimum culture condition, phytochemical constituents as well as cytotoxic activity of the endophytic fungus Xylaria hypoxylon (L.) Grev. grown on rotten bamboo poles at Jahangirnagar University campus. The fungus was first identified up to the species level, then suitable growth medium under laboratory condition was ascertained. Among the different types of culture media, Potato dextrose agar (PDA) medium was found to be the most suitable for optimum growth of this fungus at pH 6 and 30ºC. Phytochemical study of fruit body extract showed substantial presence of terpenoids, steroids, phenolic compounds, and weak presence of glycosides, falvonoids, and saponins. Brine shrimp lethality assay of the extract showed moderate cytotoxicity with LC50 value 327.00 μg/ml after 6 hours.Jahangirnagar University J. Biol. Sci. 6(2): 1-9, 2017 (December)

A New Compound from the Endophytic Fungus Xylaria sp. from Sophora tonkinensis

A new compound, 6-heptanoyl-4-methoxy-2H-pyran-2-one (1), was isolated from the endophytic fungus Xylaria sp. GDG-102 from the leaf of Sophora tonkinensis. The structure of the new compound was elucidated on the basis of 1D and 2D NMR spectra. Compound 1 showed antimicrobial activity against E. coli and S. aureus with MIC values 50 μg/mL.

Secondary Metabolites from the Endophytic Fungus Xylaria sp. hg1009

A detailed chemical investigation of the secondary metabolites produced by the endophytic fungus Xylaria sp. isolated from the stems of Isodon sculponeatus afforded six new compounds, xylariahgins A–F (1–6), two new natural products (7 and 8), along with two known compounds (9 and 10) (Fig. 1). The structures of all compounds were unambiguously established by analyzing their spectroscopic data or referring to pertinent literature. Compounds 1–8 were tested for their cytotoxic activity against five human tumor cell lines.

Xylarodons A and B, new hexaketides from the endophytic fungus Xylaria sp. SC1440

Two new hexaketides, xylarodons B (1) and C (2), were isolated from solid cultures of the endophytic fungus Xylaria sp. SC1440. The structures of these compounds were elucidated on the basis of detailed 1D, 2D NMR, and HRESIMS analysis. Their absolute configurations were established by experimental and TDDFT calculated ECD spectra. The isolated compounds were evaluated for cytotoxic and tyrosinase inhibitory activity.

Xylaropyrones B and C, new γ-pyrones from the endophytic fungus Xylaria sp. SC1440

Two new γ-pyrones, xylaropyrones B (1) and C (2), together with three known compounds, xylaropyrone (3), annularin A (4) and annularin C (5), were isolated from solid cultures of the endophytic fungus Xylaria sp. SC1440. The structures of these compounds were determined mainly by analysis of their NMR spectroscopic data. The relative configurations of 1 and 2 were assigned on the basis of J-based configurational analysis, and the absolute configurations were established by experimental and TDDFT calculated ECD spectra. The isolated compounds were evaluated for cytotoxic and tyrosinase inhibitory activity.

Amphotericin B as an inducer of griseofulvin-containing guttate in the endophytic fungus Xylaria cubensis FLe9

Microorganisms interact with each other via metabolic exchange. Several studies have revealed that microbial metabolites may act as mediators of microbial interactions. During our previous work with endophytes isolated from the Brazilian medicinal plant Lychnophora ericoides, we demonstrated that the well-known antifungal compound amphotericin B, produced by the endophytic actinobacterium Streptomyces albospinus RLe7, may trigger chemical responses in endophytic fungi. In this study, we cultured endophytic fungi in amphotericin B-enriched media to verify whether other chemical responses could be induced. Interestingly, one fungal strain showed a differential response under the tested conditions. When the fungus Xylaria cubensis FLe9 was cultured in amphotericin B-enriched media, a mycelial guttate was observed. Investigation of the fungal extracts from X. cubensis FLe9 and purification of fungal metabolites were performed using high-performance liquid chromatography coupled to a diode array detector. Isolated compounds were characterized on the basis of nuclear magnetic resonance and mass spectrometry data. Therefore, we report on the overproduction of the fungal metabolites griseofulvin (1) and dechlorogriseofulvin (2) when the endophytic fungus Xylaria cubensis FLe9 was exposed to amphotericin B. Both fungal compounds 1 and 2 were also detected in the mycelial guttate produced when X. cubensis FLe9 was exposed to amphotericin B. Since the amphotericin B-producing actinobacterium S. albospinus RLe7 and the griseofulvin-producing fungus X. cubensis FLe9 are endophytes from the same host, biosynthetic induction of fungal compounds may suggest a potential signaling role for amphotericin B in natural environments. However, this hypothesis needs to be further investigated in field experiments.