Rosellichalasins A-H, cytotoxic cytochalasans from the endophytic fungus Rosellinia sp. Glinf021.

Eight new cytochalasans rosellichalasins A-H (1-8), as well as two new shunt metabolites rosellinins A (9) and B (10) before intramolecular Diels-Alder cycloaddition reaction in cytochalasan biosynthesis, along with nine known cytochalsans (11-19) were isolated from the endophytic fungus Rosellinia sp. Glinf021, which was derived from the medicinal plant Glycyrrhiza inflata. Their structures were characterized by extensive analysis of 1D and 2D NMR as well as HRESIMS spectra and quantum chemical ECD calculations. The cytotoxic activities of these compounds were evaluated against four human cancer cell lines including HCT116, MDA-MB-231, BGC823, and PANC-1 with IC50 values ranging from 0.5 to 58.2 µM.

Antibacterial Properties of Bacterial Endophytes Isolated from the Medicinal Plant Origanum heracleoticum L.

BACKGROUND: Bacterial endophytic communities associated with medicinal plants synthesize a plethora of bioactive compounds with biological activities. Their easy isolation and growth procedures make bacterial endophytes an untapped source of novel drugs, which might help to face the problem of antimicrobial resistance. This study investigates the antagonistic potential of endophytic bacteria isolated from different compartments of the medicinal plant O. heracleoticum against human opportunistic pathogens. METHODS: A panel of endophytes was employed in cross-streaking tests against multidrug-resistant human pathogens, followed by high-resolution chemical profiling using headspace-gas chromatography/mass spectrometry. RESULTS: Endophytic bacteria exhibited the ability to antagonize the growth of opportunistic pathogens belonging to the Burkholderia cepacia complex (Bcc). The different inhibition patterns observed were related to their taxonomic attribution at the genus level; most active strains belong to the Gram-positive genera Bacillus, Arthrobacter, and Pseudarthrobacter. Bcc strains of clinical origin were more sensitive than environmental strains. Cross-streaking tests against other 36 human multidrug-resistant pathogens revealed the highest antimicrobial activity towards the Coagulase-negative staphylococci and Klebsiella pneumoniae strains. Interestingly, strains of human origin were the most inhibited, in both groups. Concerning the production of volatile organic compounds (VOCs), the strain Arthrobacter sp. OHL24 was the best producer of such compounds, while two Priestia strains were good ketones producers and so could be considered for further biotechnological applications. CONCLUSIONS: Overall, this study highlights the diverse antagonistic activities of O. heracleoticum-associated endophytes against both Bcc and multidrug-resistant (MDR) human pathogens. These findings hold important implications for investigating bacterial endophytes of medicinal plants as new sources of antimicrobial compounds.

The anticancer and antibacterial potential of bioactive secondary metabolites derived From bacterial endophytes in association with Artemisia absinthium.

The continuous search for secondary metabolites in microorganisms isolated from untapped reservoirs is an effective prospective approach to drug discovery. In this study, an in-depth analysis was conducted to investigate the diversity of culturable bacterial endophytes present in the medicinal plant A. absinthium, as well as the antibacterial and anticancer potential of their bioactive secondary metabolites. The endophytic bacteria recovered from A. absinthium, were characterized via the implementation of suitable biochemical and molecular analyses. Agar well diffusion and broth microdilution were used to screen antibacterial activity. SEM was performed to assess the impact of the extracted metabolite on MRSA strain cell morphology. Apoptosis and cytotoxicity assays were used to evaluate anticancer activity against MCF7 and A549. The FTIR, GC-MS were used to detect bioactive compounds in the active solvent fraction. Of the various endophytic bacteria studied, P. aeruginosa SD01 showed discernible activity against both bacterial pathogens and malignancies. The crude ethyl acetate extract of P. aeruginosa SD01 showed MICs of 32 and 128 µg/mL for S. aureus and MRSA, respectively. SEM examination demonstrated MRSA bacterial cell lysis, hole development, and intracellular leaking. This study revealed that the crude bioactive secondary metabolite SD01 has potent anticancer activity. In this study, 2-aminoacetophenone, 1,2-apyrazine-1,4-dione, phenazine and 2-phenyl-4-cyanopyridine were the major bioactive secondary metabolites. In conclusion, our findings indicate that the bacteria recovered from A. absinthium plants and in particular, P. aeruginosa SD01 is a remarkable source of untapped therapeutic, i.e., antimicrobial and anticancer compounds.

Production, bioprocessing and antiproliferative activity of camptothecin from Aspergillus terreus, endophyte of Cinnamomum camphora: restoring their biosynthesis by indigenous microbiome of C. camphora.

Fungal producing potency of camptothecin (CPT) raise the hope for their usage to be a platform for industrial production of CPT, nevertheless, attenuation of their productivity of CPT with the subculturing and preservation is the challenge. So, screening for novel endophytic fungal isolates with a reliable CPT-biosynthetic stability was the objective. Among the isolated endophytic fungi from the tested medicinal plants, Aspergillus terreus OQ642314.1, endophyte of Cinnamomum camphora, exhibits the highest yield of CPT (89.4 µg/l). From the NMR, FT-IR and LC-MS/MS analyses, the extracted CPT from A. terreus gave the same structure and molecular mass fragmentation pattern of authentic CPT (349 m/z). The putative CPT had a significant activity against MCF7 (0.27 µM) and HEPG-2 (0.8 µM), with a strong affinity to inhibits the human Topoisomerase 1 activity (IC50 0.362 µg/ml) as revealed from the Gel-based DNA relaxation assay. The purified CPT displayed a strong antimicrobial activity for various bacterial (E. coli and B. cereus) and fungal (A. flavus and A. parasiticus) isolates, ensuring the unique tertiary, and stereo-structure of A. terreus for penetrating the microbial cell walls and targeting the topoisomerase I. The higher dual activity of the purified CPT as antimicrobial and antitumor, emphasize their therapeutic efficiency, especially with growth of the opportunistic microorganisms due to the suppression of human immune system with the CPT uses in vivo. The putative CPT had an obvious activity against the tumor cell (MCF7) metastasis, and migration as revealed from the wound healing assay. The overall yield of A. terreus CPT was maximized with the Blackett-Burman design by twofolds increment (164.8 µg/l). The CPT yield by A. terreus was successively diminished with the multiple fungal subculturing, otherwise, the CPT productivity of A. terreus was restored, and increased over the zero culture upon coculturing with C. camphora microbiome (1.5% w/v), ensuring the restoring of CPT biosynthetic potency of A. terreus by the plant microbiome-derived chemical signals "microbial communication". This is the first report exploring the feasibility of A. terreus "endophyte of C. camphora" to be a preliminary platform for commercial production of CPT with a reliable sustainability upon uses of indigenous C. camphora microbiome.

Endophytic bacteria isolated from Urtica dioica L.- preliminary screening for enzyme and polyphenols production.

Endophytes, especially those isolated from herbal plants, may act as a reservoir of a variety of secondary metabolites exhibiting biological activity. Some endophytes express the ability to produce the same bioactive compounds as their plant hosts, making them a more sustainable industrial supply of these substances. Urtica dioica L. (common stinging nettle) is a synanthropic plant that is widely used in herbal medicine due to the diversity of bioactive chemicals it contains, e.g., polyphenols, which demonstrate anti-inflammatory, antioxidant, and anti-cancerous capabilities. This study aimed at isolating endophytic bacteria from stinging nettles for their bioactive compounds. The endophytic isolates were identified by both biochemical and molecular methods (16S rRNA) and investigated for enzymes, biosurfactants, and polyphenols production. Each of the isolated bacterial strains was capable of producing biosurfactants and polyphenols. However, three of the isolated endophytes, identified as two strains of Bacillus cereus and one strain of Bacillus mycoides, possessed the greatest capacity to produce biosurfactants and polyphenols. The derivatized extracts from culture liquid showed the 1.633 mol l-1 (9.691 mg l-1) concentration of polyphenol compounds. Therefore, the present study signifies that endophytic B. cereus and B. mycoides isolated from Urtica dioica L. could be a potential source of biosurfactants and polyphenols. However, further study is required to understand the mechanism of the process and achieve efficient polyphenol production by endophytic bacteria.

Caryophyllene Sesquiterpenes from a Chaetomium globosum Endophyte of the Canadian Medicinal Plant Empetrum nigrum.

Punctaporonins T (1) and U (2), new caryophyllene sesquiterpenes, were isolated with three known punctaporonins, A (3), B (4), and C (5), from the endophytic fungus Chaetomium globosum (TC2-041). The structures and relative configurations of punctaporonins T and U were elucidated based on a combination of HRESIMS, 1D/2D NMR spectroscopic analysis, and X-ray diffraction analysis, while their absolute configuration is presumed to be consistent with the co-isolated 3-5 on biogenetic arguments. Compound 1 showed weak inhibitory activity against both Mycobacterium tuberculosis and Staphylococcus aureus.

Bio-guided isolation of potential anti-inflammatory constituents of some endophytes isolated from the leaves of ground cherry (Physalis pruinosa L.) via ex-vivo and in-silico studies.

BACKGROUND: Due to the extensive potential of previously studied endophytes in addition to plants belonging to genus Physalis as a source of anti-inflammatory constituents, the present study aimed at isolation for the first time some endophytic fungi from the medicinal plant Physalis pruinosa. METHODS: The endophytic fungi were isolated from the fresh leaves of P. pruinosa then purified and identified by both morphological and molecular methods. Comparative evaluation of the cytotoxic and ex vivo anti-inflammatory activity in addition to gene expression of the three pro-inflammatory indicators (TNF-α, IL-1ß and INF-γ) was performed in WBCs treated with lipopolysaccharide (LPS) for the identified endophytes, isolated compounds and the standard anti-inflammatory drug (piroxicam). For prediction of the binding mode of the top-scoring constituents-targets complexes, the Schrödinger Maestro 11.8 package (LLC, New York, NY) was employed in the docking study. RESULTS: A total of 50 endophytic fungal isolates were separated from P. pruinosa leaves. Selection of six representative isolates was performed for further bioactivity screening based on their morphological characters, which were then identified as Stemphylium simmonsii MN401378, Stemphylium sp. MT084051, Alternaria infectoria MT573465, Alternaria alternata MZ066724, Alternaria alternata MN615420 and Fusarium equiseti MK968015. It could be observed that A. alternata MN615420 extract was the most potent anti-inflammatory candidate with a significant downregulation of TNF-α. Moreover, six secondary metabolites, alternariol monomethyl ether (1), 3'-hydroxyalternariol monomethyl ether (2), alternariol (3), α-acetylorcinol (4), tenuazonic acid (5) and allo-tenuazonic acid (6) were isolated from the most potent candidate (A. alternata MN615420). Among the tested isolated compounds, 3'-hydroxyalternariol monomethyl ether showed the highest anti-inflammatory potential with the most considerable reductions in the level of INF-γ and IL-1ß. Meanwhile, alternariol monomethyl ether was the most potent TNF-α inhibitor. The energy values for the protein (IL-1ß, TNF-α and INF-γ)-ligand interaction for the best conformation of the isolated compounds were estimated using molecular docking analysis. CONCLUSIONS: The results obtained suggested alternariol derivatives may serve as naturally occurring potent anti-inflammatory candidates. This study opens new avenues for the design and development of innovative anti-inflammatory drugs that specifically target INF-γ, IL-1ß and INF-γ.

Chemical and Biological Review of Endophytic Fungi Associated with Morus sp. (Moraceae) and In Silico Study of Their Antidiabetic Potential.

The chronic nature of diabetes mellitus motivates the quest for novel agents to improve its management. The scarcity and prior uncontrolled utilization of medicinal plants have encouraged researchers to seek new sources of promising compounds. Recently, endophytes have presented as eco-friendly leading sources for bioactive metabolites. This article reviewed the endophytic fungi associated with Morus species and their isolated compounds, in addition to the biological activities tested on their extracts and chemical constituents. The relevant literature was collected from the years 2008-2022 from PubMed and Web of Science databases. Notably, no antidiabetic activity was reported for any of the Morus-associated endophytic fungal extracts or their twenty-one previously isolated compounds. This encouraged us to perform an in silico study on the previously isolated compounds to explore their possible antidiabetic potential. Furthermore, pharmacokinetic and dynamic stability studies were performed on these compounds. Upon molecular docking, Colletotrichalactone A (14) showed a promising antidiabetic activity due to the inhibition of the α-amylase local target and the human sodium-glucose cotransporter 2 (hSGT2) systemic target with safe pharmacokinetic features. These results provide an in silico interpretation of the possible anti-diabetic potential of Morus endophytic metabolites, yet further study is required.

The antifeedant and antifungal cryptic metabolites isolated from tobacco endophytes induced by host medium and coculture.

Four new cryptic metabolites including one fumagillol derivative (2), one cyclohexenone derivative (4), one 10-membered lactone (5), and one natural 4-epi-brefeldin C (8), along with seven known compounds were found from isogenesis endophytes Aspergillus fumigatus, Penicillium janthinellum, Nigrospora sp., and Stagonosporopsis sp. induced by host Nicotiana tabacum medium and co-culture. The structures were determined mainly by spectroscopic methods, including extensive 1D, 2D NMR, MS techniques, ECD calculation, and Mosher's method. Compound 2 possessed a novel 1, 3-dioxetane residue and cyclohexane-containing terpenoid skeleton. Compounds 2, 4-7 and 10 showed significant antifungal activities against the plant pathogen Nigrospora sp. with MICs of 1 µg/mL. 2, 4, 5-7, and 10 indicated antifungal activities against Penicillium janthinellum, Aspergillus fumigatus, Phomopsis sp., and Alternaria sp. with MICs ≤8 µg/mL. Compounds 2, 6-8, and 10 (50 µg/cm2) and microbial fermentation extracts (100 µg/cm2) showed antifeedant activities against silkworms with feeding deterrence indices of 21-100%.

[Secondary metabolites of endophyte fungi Xylaria sp. from Coptis chinensis].

Two new polyketides, lasobutone A(1) and lasobutone B(2), along with three known compounds, guignardianone C(3), guignardic acid(4), and 4-hydroxy-17R-methylincisterol(5), were isolated from the endophytic fungi Xylaria sp. by silica gel, MCI, and preparative HPLC, which was separated from the Chinese medicinal material Coptis chinensis and cultivated through solid fermentation with rice. Their structures were elucidated on the basis of spectroscopic methods, such as MS, NMR, IR, UV, and ECD. Compounds 2 and 4 showed inhibitory activities against the nitric oxide(NO) production in the LPS-induced macrophage RAW264.7 with IC_(50) values of 58.7 and 42.5 µmol·L~(-1) respectively, while compound 5 exhibited cytotoxic activities against HT-29 with IC_(50) value of 14.3 µmol·L~(-1).

Endophytic fungi of Brunfelsia uniflora: isolation, cryopreservation, and determination of enzymatic and antioxidant activity.

Brunfelsia uniflora (Pohl.) D. Don (Solanaceae), commonly known as manacá-de-cheiro, is widely distributed in Brazil and used by local indigenous peoples as an antirheumatic, antisyphilitic, depurative, emetic, vermifuge, and purgative agent. Several studies have examined the biological activities and phytochemical profile of Brunfelsia; however, few have focused on the diversity of endophytic microorganisms that colonize members of the genus. This study aimed to isolate and cryopreserve endophytic fungi from B. uniflora and determine their cellulase, laccase, and antioxidant activities. Endophytic fungi were isolated from B. uniflora stems, cultured on wheat grains, immersed in a 150 g L-1 aqueous sucrose solution, and cryopreserved at - 80 °C for 1 and 6 months. Cellulase activity was determined by a qualitative test using carboxymethylcellulose medium and laccase activity by a quantitative test based on the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate). Prior to antioxidant activity assays, fungi were grown in malt extract broth for production of mycelial biomass. A methanolic extract was prepared for evaluation of DPPH· scavenging activity, FRAP activity, and total phenolic content. A total of 46 endophytic fungal isolates were obtained from B. uniflora stems and classified into 24 groups according to morphological similarities. B. uniflora was shown to harbor different genera of ascomycete fungi as endophytic organisms. Mycelial viability was observed after 1 and 6 months of cryopreservation at - 80 °C. Fungi exhibited cellulase and laccase activities. Isolate CE23 had the highest laccase activity after 7 days of cultivation. Twelve isolates were found to have low total phenolic contents and DPPH· and FRAP activities.

Evaluation of Phoma sp. Biomass as an Endophytic Fungus for Synthesis of Extracellular Gold Nanoparticles with Antibacterial and Antifungal Properties.

The aim of our study was to examine the different concentrations of AuNPs as a new antimicrobial substance to control the pathogenic activity. The extracellular synthesis of AuNPs performed by using Phoma sp. as an endophytic fungus. Endophytic fungus was isolated from vascular tissue of peach trees (Prunus persica) from Baft, located in Kerman province, Iran. The UltraViolet-Visible Spectroscopy (UV-Vis spectroscopy) and Fourier transform infrared spectroscopy provided the absorbance peak at 526 nm, while the X-ray diffraction and transmission electron microscopy images released the formation of spherical AuNPs with sizes in the range of 10-100 nm. The findings of inhibition zone test of Au nanoparticles (AuNPs) showed a desirable antifungal and antibacterial activity against phytopathogens including Rhizoctonia solani AG1-IA (AG1-IA has been identified as the dominant anastomosis group) and Xanthomonas oryzae pv. oryzae. The highest inhibition level against sclerotia formation was 93% for AuNPs at a concentration of 80 µg/mL. Application of endophytic fungus biomass for synthesis of AuNPs is relatively inexpensive, single step and environmentally friendly. In vitro study of the antifungal activity of AuNPs at concentrations of 10, 20, 40 and 80 µg/mL was conducted against rice fungal pathogen R. solani to reduce sclerotia formation. The experimental data revealed that the Inhibition rate (RH) for sclerotia formation was (15, 33, 74 and 93%), respectively, for their corresponding AuNPs concentrations (10, 20, 40 and 80 µg/mL). Our findings obviously indicated that the RH strongly depend on AuNPs rates, and enhance upon an increase in AuNPs rates. The application of endophytic fungi biomass for green synthesis is our future goal.

Secondary metabolites with diversified structures from an endophytic fungus Colletotrichum gloeosporioides associated with a toxic medicinal plant Tylophora ovata.

Six new secondary metabolites, including two new nor-triterpenes (1 and 2), one new sesquiterpene (4), two new α-pyrone derivatives (6 and 7), and one new natural product (5) along with two known compounds (3 and 8) were isolated from an endophytic fungus Colletotrichum gloeosporioides obtained from a toxic medicinal plant Tylophora ovata. Their structures were elucidated by spectroscopic data analyses, while their absolute configurations were determined by CD and X-ray diffraction analyses. The in vitro anti-inflammatory activities of these compounds were evaluated.

Evaluation of the antimicrobial and cytotoxic potential of endophytic fungi extracts from mangrove plants Rhizophora stylosa and R. mucronata.

Mangrove endophytic fungi are tolerant to numerous stresses and are inevitably capable of exhibiting excellent biological activity by producing impressive numbers of metabolites with special biological functions, based on previous work on the biological potential of mangrove-derived endophytic fungi. To obtain marked antimicrobial and cytotoxic fermentation products of culturable endophytic fungi from mangrove forests, our research evaluated the antimicrobial and cytotoxic activities of crude extracts of endophytic fungi from Rhizophora stylosa and Rhizophora mucronata. Forty-six fungal isolates were cultured on four different media, namely, dextrose agar (PDA), Czapek's agar (CZA), rice medium (RM) and grain medium (GM) and harvested by ethyl acetate solvent at 40 days. The extracts were tested for antimicrobial activity by the microdilution method against the gram-negative bacteria Pseudomonas adaceae (PA), gram-positive bacteria Enterococcus faecalis (EF), methicillin-resistant Staphylococcus aureus (MRSA) and pathogenic fungus Monilia albicans (MA). The cytotoxic activity of the extracts was evaluated by MTT assay using A549 human lung cancer cells, HeLa human cervical carcinoma cells, and HepG2 human hepatocellular cells. The results showed that rice medium could promote the secretion of antimicrobial and antitumour secondary metabolites of endophytic fungi in comparison with other cultivation media. Seventeen strains (68%) from R. stylosa exhibited inhibitory effects on indicators, especially N. protearum HHL46, which could inhibit the growth of four microbes with MIC values reaching 0.0625 mg/mL. Fifteen strains (71.4%) from R. mucronata displayed activities against human pathogenic microbes; in particular, Pestalotiopsis sp. HQD6 and N. protearum HQD5 could resist the growth of four microbes with MIC values ranging from 0.015 to 1 mg/mL. In the cytotoxicity assay, the extracts of 10 strains (40%), 9 strains (40%) and 13 strains (52%) of R. stylosa and 13 strains (61.9%), 10 strains (47.6%) and 10 strains (47.6%) of R. mucronata displayed cytotoxicity against A549, HeLa and HepG2 cancer cells with cell viability values ≤ 50%. Neopestalotiopsis protearum HHL46, Phomopsis longicolla HHL50, Botryosphaeria fusispora HQD83, Fusarium verticillioides HQD48 and Pestalotiopsis sp. HQD6 displayed significant antitumour activity with IC50 values below 20 µg/mL. These results highlighted the antimicrobial and antitumour potential of endophytic fungi from R. stylosa and R. mucronata and the possibility of exploiting their antimicrobial and cytotoxic agents.

New Isoquinoline Alkaloids from Paraphaeosphaeria sporulosa F03, a Fungal Endophyte Isolated from Paepalanthus planifolius.

As part of our continuing efforts to discover new bioactive compounds from endophytic fungal sources, we have investigated the extract of the Paraphaeosphaeria sporulosa F03 strain. The study led to the isolation of four new 3-methyl-isoquinoline alkaloids (1:  - 4: ) and four known polyketides (5:  - 8: ). The structures of compounds 1:  - 4: were elucidated by 1D and 2D NMR experiments and HRMS analysis. The absolute configuration of 4: was determined by comparison of its experimental electronic circular dichroism spectrum with calculated data. Compounds 1:  - 4: exhibited antifungal activity with minimal inhibitory concentration values ranging from 6.25 - 50 µg/mL against six Candida species but they did not present any cytotoxic activity against the human tumor cell lines A549 (lung), MCF-7 (breast), and HepG2 (hepatocellular). In addition, compound 4: exhibited antiplasmodial activity in the low micromolar range (IC50 = 4 µM).

Putative Anticancer Compounds from Plant-Derived Endophytic Fungi: A Review.

Endophytic fungi are microorganisms that exist almost ubiquitously inside the various tissues of living plants where they act as an important reservoir of diverse bioactive compounds. Recently, endophytic fungi have drawn tremendous attention from researchers; their isolation, culture, purification, and characterization have revealed the presence of around 200 important and diverse compounds including anticancer agents, antibiotics, antifungals, antivirals, immunosuppressants, and antimycotics. Many of these anticancer compounds, such as paclitaxel, camptothecin, vinblastine, vincristine, podophyllotoxin, and their derivatives, are currently being used clinically for the treatment of various cancers (e.g., ovarian, breast, prostate, lung cancers, and leukemias). By increasing the yield of specific compounds with genetic engineering and other biotechnologies, endophytic fungi could be a promising, prolific source of anticancer drugs. In the future, compounds derived from endophytic fungi could increase treatment availability and cost effectiveness. This comprehensive review includes the putative anticancer compounds from plant-derived endophytic fungi discovered from 1990 to 2020 with their source endophytic fungi and host plants as well as their antitumor activity against various cell lines.

Antibacterial and antioxidant activities of endophytic fungi and nettle (Urtica dioica L.) leaves as their host.

Nettle (Urtica dioica L), as a plant rich in biologically active compounds, is one of the most important plants used in herbal medicine. Studies have shown that this plant has antioxidant, antiplatelet, hypoglycemic and hypocholesterolemia effects. In this study, we characterized three Alternaria endophytic fungi isolated from their host U. dioica. We hypothesized that these endophytic fungi can produce new bioactive metabolites, which may possess the bioactive property with potential application in the medical and pharmaceutical industries. The antibacterial activity was evaluated against reference and isolated strains, including Methicillin-Resistant Staphylococcus aureus. A wide range of antimicrobial activities similar to those measured in nettle leaves was detected especially for Alternaria sorghi. Furthermore, the highest antioxidant activity detected with DPPH free radical scavenging was measured for A. sorghi and nettle leaves ethyl acetate extracts. In addition, whereas catalase activity was similar in the three isolated fungi and nettle leaves, total thiol content and superoxide dismutase activity were significantly higher in leaves. A. sorghi showed the best activities compared to other isolated fungi. The characterization and further production of bioactive compounds produced by this endophyte should be investigated to fight bacteria and especially those that develop drug multi-resistance.

Cochlioquinone derivatives produced by coculture of endophytes, Clonostachys rosea and Nectria pseudotrichia.

Three new meroterpenoid derivatives, furanocochlioquinol (1) and furanocochlioquinone (2), as well as nectrianolin D (3), together with two known biogenetically related compounds 4 and 5 were isolated from a mixed culture of two mangrove-derived fungi, Clonostachys rosea B5-2 and Nectria pseudotrichia B69-1. The structures of 1-3 were deduced based on the interpretation of HRMS and NMR data. Compounds 1-5 exhibited cytotoxicity against human promyelocytic leukemia (HL60) cells with IC50 values ranging from 0.47 to 10.16 µM.

The selective anti-fungal metabolites from Irpex lacteus and applications in the chemical interaction of Gastrodia elata, Armillaria sp., and endophytes.

The investigation of the metabolites from endophyte Irpex lacteus cultured in host "tian ma" (Gastrodia elata) revealed five new tremulane sesquiterpenes (1-5), and a new tetrahydrofuran derivative (6). Compound 1 was the first tremulane glucoside, and 6 possessed a rare tetrahydropyran-tetrahydrofuran scaffold. Main metabolite (2,3-dihydroxydodacane-4,7-dione, 14) from I. lacteus showed significant selectivity for antifungal activity against phytopathogen and endophytes associated with G. elata rather than against Armillaria sp. providing nutrition for the host G. elata. 14 accounted for 27.4% of isolated compounds from G. elata medium, and 69.3% by co-culturing with Armillaria sp. So the I. lacteus tended to promote the growth of Armillaria sp. in co-culture by producing 2,3-dihydroxydodacane-4,7-dione (14) to selective inhibit the phytopathogen and endophyte existed in host G. elata for the benefit of G. elata-Armillaria symbiosis. And the results were in accord with the real environment of G. elata depending on the nutrition of Armillaria. Some metabolites had anti-fungal activities against phytopathogens of G. elata with MICs ≤8 µg/mL.

Secondary metabolites of endophytic fungi isolated from Huperzia serrata.

The natural product Huperzine A isolated from Huperzia serrata is a targeted inhibitor of acetylcholinesterase that has been approved for clinical use in the treatment of Alzheimer's disease. Given the large demand for natural sources of Huperzine A  (Hup. A), efforts have been made to explore whether it is also produced by endophytic fungi from H. serrata and, if so, identify its biosynthetic pathway. These studies have indicated that endophytic fungi from H. serrata represent a huge and largely untapped resource for natural products (including Hup. A) with chemical structures that have been optimized by evolution for biological and ecological relevance. To date, more than three hundred endophytic fungi have been isolated from H. serrata, of which 9 strains can produce Hup. A, whilst more than 20 strains produce other important metabolites, such as polyketones, xanthones, alkaloids, steroids, triterpenoids, furanone derivatives, tremulane sesquitepenes and diterpenoids. In total, 200 secondary metabolites have been characterized in endophytic fungi from H. serrata to date. Functionally, some have cholinesterase-inhibitory or antibacterial activity. This review also considers the different classes of secondary metabolites produced by endophytic fungi, along with their possible applications. We systematically describe the taxonomy, biology, and chemistry of these secondary metabolites. It also summarizes the biosynthetic synthesis of metabolites, including that of Hup. A. The review will aid researchers in obtaining a clearer understanding of this plant-endophyte relationship to better exploit the excellent resources it offers that may be utilized by pharmaceutical industries.