Endophytic Fungus Talaromyces Research Articles

Mining of Meroterpenoids with Anti-inflammatory Activity from the Mangrove Endophytic Fungus Talaromyces sp. JNQQJ-4 by Genome Analysis and Molecular Network Strategy.

Talaromeroterpenoids A-G (1-7), seven new 3,5-dimethylorsellinic-acid-derived meroterpenoids, and two known analogues (8 and 9) were isolated from the mangrove endophytic fungus Talaromyces sp. JNQQJ-4 by genome analysis and a molecular networking strategy. Their structures and absolute configurations were established by nuclear magnetic resonance data, high-resolution electrospray ionization mass spectrometry, and X-ray diffraction. Compound 1 possesses an unprecedented rearrangement 7/6/6/5/5/5 hexacyclic skeleton based on a 2,8,18,21-tetraoxa-hexacyclo-[12.5.2.13,12.01,16.04,10.016,22]docosane core. In bioassays, compound 2 exhibited promising anti-inflammatory activity by suppressing the expression of pro-inflammatory factors and inactivating the NF-κB signaling pathway.

Congested heptacyclic meroterpenoids with anti-SARS-CoV-2 and anti-inflammatory activities from mangrove endophytic fungus Talaromyces amestolkiae SCNU–F0041

Under the guidance of LC‒MS/MS-based molecular networking, three previously undescribed berkeleyacetal type meroterpenoids, amestolknoids A-C (1–3), together with ten known analogues (4–13) were isolated and identified from the mangrove endophytic fungus Talaromyces amestolkiae SCNU–F0041. Amestolknoids A (1) and B (2) are unprecedentedly congested 6/7/6/5/5/5/5 heptacyclic scaffolds characterized by two chiral spiroketal centers. Amestolknoids A (1) and C (3) represent the first examples of chlorinated berkeleyacetal type meroterpenoids. Their structures were established by extensive spectroscopic analyses and single crystal X-ray diffraction. Bioassays revealed that amestolknoid C (3) exhibited excellent antiviral activity against SARS-CoV-2 with an EC50 value of 2.50 μM and strong inhibitory effects on nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells with an IC50 value of 4.10 μM. Compounds 2, 4, 6, 9 and 11 showed moderate to good anti-inflammatory activities with IC50 values of 41.78, 3.91, 43.52, 20.79, and 33.26 μM, respectively.

Talarindigotin A: a cytotoxic indigotin derivative, from the mangrove endophytic fungus Talaromyces amestolkiae SCNU-F0041

A new indigotin alkaloid, named talarindigotin A (1), along with the analogue 5H, 6H-quinindolin-11-one (2) were isolated from the mangrove endophytic fungus Talaromyces amestolkiae SCNU-F0041. Their structures were assigned on the basis of NMR, HRMS, and single-crystal X-ray diffraction analysis. In the cytotoxic bioassay, compound 1 showed great cytotoxicity against HepG2, Hela, HCT116, and Huh7 human cancer cell lines with IC50 values ranging from 2.08 to 4.58 μM.

Talarmalnoids A–F: Fusicoccane diterpenoids from an arthropod-derived endophytic fungus Talaromyces malicola

The metabolites from the endophytic fungus Talaromyces malicola hosted in the gastrointestinal tract of the arthropods Armadillidium vulgare were investigated, and six undescribed fusicoccane diterpenoids, talarmalnoids A–F (1–6), along with three known analogs were isolated. Talarmalnoid C (3) was an unprecedented fusicoccane diterpenoid with two sugar units, i.e., 6-O-methyl-α-d-glucose and α-d-glucose. Talarmalnoids D and E (4 and 5) were fusicoccane-type diterpenoids with unusual seven-membered rings attached at the C-3′ and C-4′ positions. Their structures and absolute configurations were identified by NMR, HRESIMS analyses, X-ray single crystal diffraction, GC–MS, ECD analyses, 13C NMR calculations, and DP4+ probability analyses. Bioassay results showed that talarmalnoid B (2) exhibited significant inhibitory activities against the LPS-inducted production of NO in RAW 264.7 cells, with IC50 value of 0.83 μM.

Sweet flavor compounds produced by the endophytic fungus Talaromyces funiculosus

Sweet flavor compounds produced by the endophytic fungus Talaromyces funiculosus

Enhanced production of health-promoting phenolic compounds using a novel endophytic fungus Talaromyces neorugulosus R-209 isolated from pigeon pea in a natural habitat by l-phenylalanine feeding.

In this study, nine endophytic fungi capable of producing multiple phenolic compounds were screened and identified from 152 fungi isolated from pigeon pea in a natural habitat (Honghe, Yunnan Province, China). Talaromyces neorugulosus R-209 exhibited the highest potential for phenolic compound production. L-phenylalanine feeding was used to enhance phenolic compound production in T. neorugulosus R-209 cultures. Under the optimal feeding conditions (l-phenylalanine dose of 0.16g/L and feeding phase of 6 days), the yields of genistein, apigenin, biochanin A, and cajaninstilbene acid increased by 15.59-fold, 7.20-fold, 25.93-fold, and 10.30-fold over control, respectively. T. neorugulosus R-209 fed with l-phenylalanine was found to be stable in the production of phenolic compounds during ten successive subcultures. Moreover, bioactivities of extracts of T. neorugulosus R-209 cultures were significantly increased by l-phenylalanine feeding. Overall, l-phenylalanine feeding strategy made T. neorugulosus R-209 more attractive as a promising alternative source for the production of health-beneficial phenolic compounds in the nutraceutical/medicinal industries.

Biocontrol potential and growth-promoting effect of endophytic fungus Talaromyces muroii SD1-4 against potato leaf spot disease caused by Alternaria alternata

BackgroundAlternaria alternata is the primary pathogen of potato leaf spot disease, resulting in significant potato yield losses globally. Endophytic microorganism-based biological control, especially using microorganisms from host plants, has emerged as a promising and eco-friendly approach for managing plant diseases. Therefore, this study aimed to isolate, identify and characterize the endophytic fungi from healthy potato leaves which had great antifungal activity to the potato leaf spot pathogen of A. alternata in vitro and in vivo.ResultsAn endophytic fungal strain SD1-4 was isolated from healthy potato leaves and was identified as Talaromyces muroii through morphological and sequencing analysis. The strain SD1-4 exhibited potent antifungal activity against the potato leaf spot pathogen A. alternata Lill, with a hyphal inhibition rate of 69.19%. Microscopic and scanning electron microscope observations revealed that the strain SD1-4 grew parallel to, coiled around, shrunk and deformed the mycelia of A. alternata Lill. Additionally, the enzyme activities of chitinase and β-1, 3-glucanase significantly increased in the hyphae of A. alternata Lill when co-cultured with the strain SD1-4, indicating severe impairment of the cell wall function of A. alternata Lill. Furthermore, the mycelial growth and conidial germination of A. alternata Lill were significantly suppressed by the aseptic filtrate of the strain SD1-4, with inhibition rates of 79.00% and 80.67%, respectively. Decrease of leaf spot disease index from 78.36 to 37.03 was also observed in potato plants treated with the strain SD1-4, along with the significantly increased plant growth characters including plant height, root length, fresh weight, dry weight, chlorophyll content and photosynthetic rate of potato seedlings.ConclusionThe endophyte fungus of T. muroii SD1-4 isolated from healthy potato leaves in the present study showed high biocontrol potential against potato leaf spot disease caused by A. alternata via direct parasitism or antifungal metabolites, and had positive roles in promoting potato plant growth.

Efficient Stereoselective Biotransformation of Prochiral Carbonyls by Endophytic Fungi from Handroanthus impetiginosus

Endophytic microorganisms are promising sources for new biocatalysts as they must deal with their host plants’ chemicals by developing adaptative strategies, such as enzymatic pathways. As part of our efforts in selecting endophytic strains as biocatalysts, this study describes the screening of endophytic fungi isolated from Handroanthus impetiginosus leaves for selective bioreduction of Acetophenone. The bioreductions were monitored by chiral gas chromatography and conducted to the selection of the endophyte Talaromyces sp. H4 as capable of reducing acetophenone to (S)-1-phenylethanol in excellent conversion and enantiomeric excess rates. The influence of seven parameters on the stereoselective bioreduction of acetophenone by Talaromyces sp. H4 was studied: reaction time, inoculum charge, shaking, pH, temperature, substrate concentration, and co-solvent. The optimal conditions were then used to reduce substituted acetophenones and Acetophenone scale-up, which furnished (S)-1-Phenylethanol in 73% yield and 96% ee. The results highlight the endophytic fungus Talaromyces sp. H4 as an excellent biocatalyst for stereoselective reduction of prochiral carbonyls.

Activation of a Silent Gene Cluster from the Endophytic Fungus Talaromyces sp. Unearths Cryptic Azaphilone Metabolites.

Fungal azaphilones have attracted widespread attention due to their significant potential as sources of food pigments and pharmaceuticals. Genome mining and gene cluster activation represent powerful tools and strategies for discovering novel natural products and bioactive molecules. Here, a putative azaphilone biosynthetic gene cluster lut from the endophytic fungus Talaromyces sp. was identified through genome mining. By overexpressing the pathway-specific transcription factor LutB, five new sclerotiorin-type azaphilones (1, 6, 8, and 10-11) together with seven known analogues (2-5, 7, 9, 12) were successfully produced. Compounds 8 and 9 exhibited antibacterial activity against Bacillus subtilis with MIC values of 64 and 16 μg/mL, respectively. Compound 11 showed cytotoxic activity against HCT116 and GES-1 with IC50 values of 10.9 and 4.9 μM, respectively, while 1, 4, 5, and 7-10 showed no obvious cytotoxic activity. Gene inactivation experiments confirmed the role of the lut cluster in the production of compounds 1-12. Subsequent feeding experiments unveiled the novel functional diversity of the dual megasynthase system. Furthermore, a LutC-LutD binary oxidoreductase system was discovered, and in combination with DFT calculations, the basic biosynthetic pathway of the sclerotiorin-type azaphilones was characterized. This study provided a good example for the discovery of new azaphilones and further uncovered the biosynthesis of these compounds.

Talaesthanes A–C, three new meroterpenoids from the endophytic fungus Talaromyces primulinus H21

Three new meroterpenoids (1–3) and ten known ones (4–13) were obtained from the endophytic fungus Talaromyces primulinus H21 isolated from the plant of Euphorbia sikkimensis. Their structures including their absolute configurations were elucidated by extensive analysis of spectroscopic data such as HR-ESI-MS, 1D/2D NMR, and X-ray diffraction of single crystal together with comparison of experimental ECD with calculated ECD. All compounds were examined for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 cells, and compounds 3, 9, 12, and 13 exhibited certain inhibition on NO production, with IC50 values of 27.19, 41.55, 25.23, and 24.71 μM, respectively.

Talaroacids A-D and Talaromarane A, Diterpenoids with Anti-Inflammatory Activities from Mangrove Endophytic Fungus Talaromyces sp. JNQQJ-4.

Five new diterpenes including four diterpenes with 1,2,3,4,4a,5,6,8a-octalin skeleton talaroacids A-D (1-4) and an isopimarane diterpenoid talaromarane A (5) were isolated from the mangrove endophytic fungus Talaromyces sp. JNQQJ-4. Their structures and absolute configurations were determined by analysis of high-resolution electrospray ionization mass spectroscopy (HRESIMS), 1D/2D Nuclear Magnetic Resonance (NMR) spectra, single-crystal X-ray diffraction, quantum chemical calculation, and electronic circular dichroism (ECD). Talaromarane A (5) contains a rare 2-oxabicyclo [3.2.1] octan moiety in isopimarane diterpenoids. In bioassays, compounds 1, 2, 4, and 5 displayed significant anti-inflammatory activities with the IC50 value from 4.59 to 21.60 μM.

New polyketides and cytotoxic alkaloids from the mangrove endophytic fungus Talaromyces sp. SAF14

Investigation of secondary metabolites from the mangrove endophytic fungus Talaromyces sp. SAF14 led to the isolation of two new polyketides, methyl (R)-3-(6,8-dihydroxy-7-methoxy-1-oxoisochroman-3-yl)propanoate (1), (R)-3-(5,8- dihydroxy-1-oxoisochroman-3-yl)propanoic acid (2), together with four known alkaloids (3–6). The planar structures of new compounds were elucidated by comprehensive analysis of HR-ESI-MS and NMR data. The absolute configurations were determined by comparison of the calculated ECD spectrum with the measured one. All the isolated compounds were tested for cytotoxic activities against three human cancer cell lines. The known beauvericin (3) exhibited strong cytotoxic activity against A549, MCF-7, and KB cell lines with IC50 values of 5.36 ± 2.49, 1.96 ± 1.09 and 4.46 ± 0.68 μM, respectively.

A derivative of trihydroxynaphthalenone and a pyrone metabolite from the endophytic fungus Talaromyces purpurpgenus

A newly discovered trihydroxynaphthalenone derivative, epoxynaphthalenone (1) involving the condensation of ortho-hydroxyl groups into an epoxy structure, and a novel pyrone metabolite characterized as pyroneaceacid (2), were extracted from Talaromyces purpurpgenus, an endophytic fungus residing in Rhododendron molle. The structures of these compounds were elucidated through a comprehensive analysis of their NMR and HRESIMS data. The determination of absolute configurations was accomplished using electronic circular dichroism (ECD) calculations and CD spectra. Notably, these recently identified metabolites exhibited a moderate inhibitory activity against xanthine oxidase (XOD).

4-Hydroxy-2-pyridone derivatives with antitumor activity produced by mangrove endophytic fungus Talaromyces sp. CY-3

OSMAC strategy is a useful tool for discovering series of metabolites from microorganism. Five new sambutoxin derivatives (1–2, 4, 8–9), together with seven known compounds (3, 5–7, 10–12), were isolated from Talaromyces sp. CY-3 under OSMAC strategy and guidance of molecular networking. Their planar structures and absolute configurations were determined by NMR, HRESIMS, ECD spectra and common biosynthetic pathway. In bioassay, compounds 1–12 showed cytotoxicity to tumor cell lines with IC50 values in the range of 1.76–49.13 μM. The antitumor molecular mechanism of 10 was also explored. In vitro compound 10 significantly inhibited the growth and proliferation of two lung cancer cell lines (A549 and H1703). Furthermore, colony formation, EdU analysis, flow cytometry and Western blot analysis showed that 10 could induce cell cycle arrest in G0/G1 phase by promoting the expression of p53 and p21. The molecular mechanism of its antitumor effects in vitro is that 10 arrests the cell cycle by activating the p21/CyclinD1/Rb signaling pathway and the p53 pathway. Our results identified a lead small molecule compound with efficient antitumor growth and proliferation activity.

Isolation and Identification of Acer truncatum Endophytic Fungus Talaromyces verruculosus and Evaluation of Its Effects on Insoluble Phosphorus Absorption Capacity and Growth of Cucumber Seedlings.

The symbiosis between endophytic fungi and plants can promote the absorption of potassium, nitrogen, phosphorus, and other nutrients by plants. Phosphorus is one of the indispensable nutrient elements for plant growth and development. However, the content of available phosphorus in soil is very low, which limits the growth of plants. Phosphorus-soluble microorganisms can improve the utilization rate of insoluble phosphorus. In this study, Talaromyces verruculosus (T. verruculosus), a potential phosphorus-soluble fungus, was isolated from Acer truncatum, a plant with strong stress resistance, and its phosphorus-soluble ability in relation to cucumber seedlings under different treatment conditions was determined. In addition, the morphological, physiological, and biochemical indexes of the cucumber seedlings were assessed. The results show that T. verruculosus could solubilize tricalcium phosphate (TCP) and lecithin, and the solubilization effect of lecithin was higher than that of TCP. After the application of T. verruclosus, the leaf photosynthetic index increased significantly. The photosynthetic system damage caused by low phosphorus stress was alleviated, and the root morphological indexes of cucumber seedlings were increased. The plant height, stem diameter, and leaf area of cucumber seedlings treated with T. verruculosus were also significantly higher than those without treatment. Therefore, it was shown that T. verruculosus is a beneficial endophytic fungus that can promote plant growth and improve plant stress resistance. This study will provide a useful reference for further research on endophytic fungi to promote growth and improve plant stress resistance.

Genome mining and AntiSMASH analysis of an Endophytic Talaromyces sp. reveal biosynthetic pathway gene clusters for novel bioactive compounds

Medicinal plants and their endophytes are one of the efficient producers of diverse secondary metabolites with therapeutic importance. In the present study, an endophytic fungus Talaromyces spp. isolated from Syzygium samarangense was subjected to whole-genome sequencing and Antibiotics and Secondary Metabolite Analysis Shell (AntiSMASH) annotation to identify biosynthetic gene clusters (BGCs) of secondary metabolites and their biosynthetic pathways. The Funannotate results revealed that the Talaromyces isolate has a total of 30.5Mb genome consisting of 372 contigs, 372 scaffolds and 47.64% GC content. In addition, 114 tRNA, 12722 functional mRNA, 12721 CDS transcripts, and 12721 protein-coding sequences were predicted and annotated using various BLAST databases. AntiSMASH revealed the presence of 76 BGCs, including 28 T1 Polyketide synthase (T1 PKS), 10 Nonribosomal peptide synthetases (NRPSs), 9 terpene, 1 Indole, 12 NRPs like, 4 T1 PKS and NRPs like, 2 T1 PKS Indole, 1 NRPs like terpene, 3 NRPs T1 PKS, 1 Indole NRPs, 2 betalactone, 1 phosphonate, 1 fungal-RiPP T1 PKS and 1 Other type. The analysis also predicted the occurrence of enzymes involved in the biosynthesis of some of the important secondary metabolites such as Pyranonigrin, Squalestatin -S, Azanigerone -A, Asperterpenoid -A, Napthopyrone, Clavaric acid, and Fusarin.

Draft genome sequence of endophytic fungus Talaromyces purpureogenus strain YAFEF302, isolated from Juglans sigillata.

Here, we report a draft genome sequence of endophytic fungus Talaromyces purpureogenus strain YAFEF302, isolated from Juglans sigillata. The genome resource will support future research into potential secondary metabolite diversity of this fungus.

New Dipyrroloquinones from a Plant-Derived Endophytic Fungus Talaromyces sp.

Two new dipyrroloquinones, namely talaroterreusinones A (1) and B (2), together with four known secondary metabolites, terreusinone A (3), penicillixanthone A (4), isorhodoptilometrin (5), and chrysomutanin (6), were isolated from the solid culture of the endophytic fungus Talaromyces sp. by integrating mass spectrometry-based metabolic profiling and a bioassay-guided method. Their planar structures and stereochemistry were elucidated by comprehensive spectroscopic analysis including NMR and MS. The absolute configuration at C-1″ of terreusinone A (1) was established by applying the modified Mosher’s method. Compounds 1–6 were evaluated for anti-inflammatory activity and cytotoxicity. As a result, 1–3 inhibited the LPS-stimulated NO production in macrophage RAW264.7 cells, with IC50 values of 20.3, 30.7, and 20.6 µM, respectively. Penicillixanthone A (4) exhibited potent cytotoxic activity against Hep G2 and A549 cell lines, with IC50 values of 117 nM and 212 nM, respectively, and displayed significant antitumour effects in A549 cells by inhibiting the PI3K-Akt-mTOR signalling pathway.

New Meroterpenoid Derivatives from the Pomegranate-Derived Endophytic Fungus Talaromyces purpureogenus.

In this study, we report the isolation of two new meroterpenoids, miniolutelide D (1) and miniolutelide E (13-epi-miniolutelide C) (2), along with two meroterpenoidal analogues (3 and 4) and two phenolic compounds (5 and 6) from the endophytic fungus Talaromyces purpureogenus derived from Punica granatum fruits. Their structures were elucidated using extensive MS, 1D, and 2D NMR spectroscopic analyses as well as by comparing with data in the literature. The absolute configurations of 1 and 2 were determined using TDDFT-ECD calculations. Antimicrobial activity was evaluated. Compound 5 displayed significant activity against methicillin-resistant Staphylococcus aureus strain ATCC 700699 and moderate activity against S. aureus strain ATCC 29213.

Procaine treatment altered metabolite profiles of endophytic fungus Talaromyces wortmannii collected from Morus cathayana Hemsl

Chemical epigenetic modifiers could optimize the compound biosynthesis of endophytes by activating the silent genes. Treatment of procaine, an epigenetic modifier, on endophytic fungus Talaromyces wortmannii isolated from Morus Cathayana Hemsl., was evaluated with NMR spectroscopy analysis combined with multivariate data analysis and antibacterial assay. In total, 29 compounds were successfully annotated in the T. wortmannii extracts and most of them are primary metabolites. Semi-quantitative 1H NMR analysis revealed that the concentrations of some annotated compounds increased in the treated endophyte, including wortmin, mannitol, and choline. Meanwhile, the contents of glucose and skyrin decreased in the treated T. wortmannii. Multivariate data analysis successfully distinguished the metabolite profile of the treated T. wortmannii from that of the control endophyte. This analysis revealed that procaine treatment on T. wortmannii possibly induced the biosynthesis of mannitol, choline, lactic acid, and phosphocholine and repressed the contents of fatty acids, including palmitic, stearic, linoleic, and oleic acids. The antibacterial assay revealed chloroform extracts of the treated endophyte, and its control possessed potent antibacterial activity against the tested pathogenic bacteria. Meanwhile, the antibacterial activity of water-methanol extract of the treated T. wortmannii increased against Enterococcus faecalis and Salmonella enterica. In this report, the procaine treatment altered the metabolite profiles of the endophytic fungus T. wortmannii. Here we also demonstrated that 1H NMR-based metabolomics was the effective method to study the effect of the epigenetic modifier on endophytic fungi.