[Secondary metabolites of endophytic fungus Talaromyces malicola hosted in Armadillidium vulgare].

The secondary metabolites of the endophytic fungus Talaromyces malicola hosted in the arthropod Armadillidium vulgare were separated by silica gel column chromatography, gel column chromatography, and semi-preparative high-performance liquid chromatography. Eleven compounds(1-11) were obtained from the ethyl acetate fraction of the fermentation broth of T. malicola, and their structures were identified by NMR, HR-ESI-MS, UV, IR, and ECD. The 11 compounds were talarosesquiterpene A(1),(3ß,5α,6α,15α,22E)-5,6-epoxyergosta-8(14),22-diene-3,7,15-triol(2), vermistatin(3), hydroxyvermistatin(4), bercheminol A(5), penicillide(6), lunatinin(7), penipurdin A(8), emodin(9), BE-25327(10), and(-)-regiolone(11). Compound 1 was a new diaporol-type sesquiterpene. Compounds 2, 4-5, and 7-11 were isolated from Talaromyces for the first time.

New Sesquiterpenoids from the Mangrove-Derived Fungus Talaromyces sp. as Modulators of Nuclear Receptors.

Four new sesquiterpenoids, talaroterpenes A-D (1-4), were isolated from the mangrove-derived fungus Talaromyces sp. SCSIO 41412. The structures of compounds 1-4 were elucidated through comprehensive NMR and MS spectroscopic analyses. The absolute configurations of 1-4 were assigned based on single-crystal X-ray diffraction and calculated electronic circular dichroism analysis. Talaroterpenes A-D (1-4) were evaluated with their regulatory activities on nuclear receptors in HepG2 cells. Under the concentrations of 200 µM, 1, 3 and 4 exhibited varying degrees of activation on ABCA1 and PPARα, while 4 showed the strongest activities. Furthermore, 4 induced significant alterations in the expression of downstream target genes CLOCK and BMAL1 of RORα, and the in silico molecular docking analysis supported the direct binding interactions of 4 with RORα protein. This study revealed that talaroterpene D (4) was a new potential non-toxic modulator of nuclear receptors.

Penicillides from Penicillium and Talaromyces: Chemical Structures, Occurrence and Bioactivities.

Penicillide is the founder product of a class of natural products of fungal origin. Although this compound and its analogues have been identified from taxonomically heterogeneous fungi, they are most frequently and typically reported from the species of Talaromyces and Penicillium. The producing strains have been isolated in various ecological contexts, with a notable proportion of endophytes. The occurrence of penicillides in these plant associates may be indicative of a possible role in defensive mutualism based on their bioactive properties, which are also reviewed in this paper. The interesting finding of penicillides in fruits and seeds of Phyllanthus emblica is introductory to a new ground of investigation in view of assessing whether they are produced by the plant directly or as a result of the biosynthetic capacities of some endophytic associates.

Antiviral Chlorinated Drimane Meroterpenoids from the Fungus Talaromyces pinophilus LD-7 and Their Biosynthetic Pathway.

Ten new drimane meroterpenoids talarines A-J (1-10), along with six known analogues (11-16), were isolated from desert soil-derived fungus Talaromyces pinophilus LD-7. Their 2D structures were elucidated by comprehensive interpretation of NMR and HRESIMS data. Electronic circular dichroism calculation was used to establish their absolute configurations. Compounds 2, 10, and 11 showed antiviral activities toward vesicular stomatitis virus with IC50 values of 18, 15, and 23 nM, respectively. The structure-bioactivity relationship indicated that chlorine substitution at C-5 contributed greatly to their antiviral activities. Finally, we identified a new halogenase outside the biosynthetic gene cluster, which was responsible for C-5 halogenation of the precursor isocoumarin 17 as a tailoring step in chlorinated meroterpenoids assembly.

Three-Step Enzymatic Remodeling of Chitin into Bioactive Chitooligomers.

Here we describe a complex enzymatic approach to the efficient transformation of abundant waste chitin, a byproduct of the food industry, into valuable chitooligomers with a degree of polymerization (DP) ranging from 6 to 11. This method involves a three-step process: initial hydrolysis of chitin using engineered variants of a novel fungal chitinase from Talaromyces flavus to generate low-DP chitooligomers, followed by an extension to the desired DP using the high-yielding Y445N variant of ß-N-acetylhexosaminidase from Aspergillus oryzae, achieving yields of up to 57%. Subsequently, enzymatic deacetylation of chitooligomers with DP 6 and 7 was accomplished using peptidoglycan deacetylase from Bacillus subtilis BsPdaC. The innovative enzymatic procedure demonstrates a sustainable and feasible route for converting waste chitin into unavailable bioactive chitooligomers potentially applicable as natural pesticides in ecological and sustainable agriculture.

Chitinase-functionalized UiO-66 framework nanoparticles active against multidrug-resistant Candida Auris.

Candida auris (C. auris) is a yeast that has caused several outbreaks in the last decade. Cell wall chitin plays a primary role in the antifungal resistance of C. auris. Herein, we investigated the potential of chitinase immobilized with UiO-66 to act as a potent antifungal agent against C. auris. Chitinase was produced from Talaromyces varians SSW3 in a yield of 8.97 U/g dry substrate (ds). The yield was statistically enhanced to 120.41 U/g ds by using Plackett-Burman and Box-Behnken design. We synthesized a UiO-66 framework that was characterized by SEM, TEM, XRD, FTIR, a particle size analyzer, and a zeta sizer. The produced framework had a size of 70.42 ± 8.43 nm with a uniform cubic shape and smooth surface. The produced chitinase was immobilized on UiO-66 with an immobilization yield of 65% achieved after a 6 h loading period. The immobilization of UiO-66 increased the enzyme activity and stability, as indicated by the obtained Kd and T1/2 values. Furthermore, the hydrolytic activity of chitinase was enhanced after immobilization on UiO-66, with an increase in the Vmax and a decrease in the Km of 2- and 38-fold, respectively. Interestingly, the antifungal activity of the produced chitinase was boosted against C. auris by loading the enzyme on UiO-66, with an MIC50 of 0.89 ± 0.056 U/mL, compared to 5.582 ± 0.57 U/mL for the free enzyme. This study offers a novel promising alternative approach to combat the new emerging pathogen C. auris.

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.

New Cytotoxic γ-Lactam Alkaloids from the Mangrove-Derived Fungus Talaromyces hainanensis sp. nov. Guided by Molecular Networking Strategy.

The fungus Talaromyces hainanensis, isolated from the mangrove soil, was characterized as a novel species by morphology observation and phylogenetic analyses. Four new γ-lactam alkaloids talaroilactams A-D (1-4) and two reported compounds harzianic acid (5) and isoharzianic acid (6) were identified from the fungus T. hainanensis WHUF0341, assisted by OSMAC along with molecular networking approaches. Their structures were determined through ECD calculations and spectroscopic analyses. Moreover, the biosynthetic route of 1-4 was also proposed. Compound 1 displayed potent cytotoxicity against HepG2 cell lines, with an IC50 value of 10.75 ± 1.11 µM. In addition, network pharmacology was employed to dissect the probable mechanisms contributing to the antihepatocellular carcinoma effects of compound 1, revealing that cytotoxicity was mainly associated with proteolysis, negative regulation of autophagy, inflammatory response, and the renin-angiotensin system. These results not only expanded the chemical space of natural products from the mangrove associated fungi but also afforded promising lead compounds for developing the antihepatocellular carcinoma agents.

Adpressins A-G: Oligophenalenone Dimers from Talaromyces adpressus.

Nine new oligophenalenone dimers, adpressins A-G (1-9), together with nine known compounds (10-18), were isolated from the fungus Talaromyces adpressus. Their chemical structures were determined on the basis of spectroscopic and mass spectral analyses. Their relative and absolute configurations were identified by 1H and 13C NMR calculations followed by DP4+ analyses, electronic circular dichroism (ECD) calculations, and ECD spectra comparison with related compounds. Compound 1 is the first example of a duclauxin derivative featuring an unusual 6/6/6/5/6/6/6 ring system, while compounds 6 and 7 contained a novel pyrrolidine ring. Compounds 5, 9, and 18 exhibited moderate inhibition against LPS-induced B lymphocyte proliferation with IC50 values ranging from 1.6 to 8.6 µM. Additionally, compounds 9 and 18 exhibited moderate inhibition against Con A-induced T lymphocyte proliferation with IC50 values of 9.3 and 2.6 µM, respectively.

Discovery of Oxidized p-Terphenyls as Phosphodiesterase 4 Inhibitors from Marine-Derived Fungi.

Four new p-terphenyl derivatives, talaroterphenyls A-D (1-4), together with three biosynthetically related known ones (5-7), were obtained from the mangrove sediment-derived Talaromyces sp. SCSIO 41412. Compounds 1-3 are rare p-terphenyls, which are completely substituted on the central benzene ring by oxygen atoms; this is the first report of their isolation from natural sources. Their structures were elucidated through NMR spectroscopy, HRESIMS, and X-ray diffraction. Genome sequence analysis revealed that 1-7 were biosynthesized from tyrosine and phenylalanine, involving four key biosynthetic genes (ttpB-ttpE). These p-terphenyls (1-7) and 36 marine-derived terphenyl analogues (8-43) were screened for phosphodiesterase 4 (PDE4) inhibitory activities, and 1-5, 14, 17, 23, and 26 showed notable activities with IC50 values of 0.40-16 µM. The binding pattern of p-terphenyl inhibitors 1-3 with PDE4 were explored by molecular docking analysis. Talaroterphenyl A (1), with a low cytotoxicity, showed obvious anti-inflammatory activity in LPS-stimulated RAW264.7 cells. Furthermore, in the TGF-ß1-induced medical research council cell strain-5 (MRC-5) pulmonary fibrosis model, 1 could down-regulate the expression levels of FN1, COL1, and α-SMA significantly at concentrations of 5-20 µM. This study suggests that the oxidized p-terphenyl 1, as a marine-derived PDE4 inhibitor, could be used as a promising antifibrotic agent.

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.

New Secondary Metabolites from Marine-Derived Fungus Talaromyces minnesotensis BTBU20220184.

Six new compounds, talamitones A and B (1 and 2), demethyltalamitone B (3), talamiisocoumaringlycosides A and B (4 and 5), and talaminaphtholglycoside (6), together with six known compounds (7-12), were isolated from the marine-derived fungus Talaromyces minnesotensis BTBU20220184. The new structures were characterized by using HRESIMS and NMR. This is the first report of isocoumaringlycoside derivatives from a fungus of the Talaromyces genus. Compounds 5, 6, and 9 showed synergistic antibacterial activity against Staphylococcus aureus.

Cytotoxic Pentaketide-Sesquiterpenes from the Marine-Derived Fungus Talaromyces variabilis M22734.

Talaromyces, a filamentous fungus widely distributed across terrestrial and marine environments, can produce a diverse array of natural products, including alkaloids, polyketones, and polyketide-terpenoids. Among these, chrodrimanins represented a typical class of natural products. In this study, we isolated three previously undescribed pentaketide-sesquiterpenes, 8,9-epi-chrodrimanins (1-3), along with eight known compounds (4-11). The structures of compounds 1-3 were elucidated using nuclear magnetic resonance (NMR) and mass spectrometry (MS), while their absolute configurations were determined through X-ray crystallography and electronic circular dichroism (ECD) computations. The biosynthetic pathways of compounds 1-3 initiate with 6-hydroxymellein and involve multiple stages of isoprenylation, cyclization, oxidation, and acetylation. We selected four strains of gastrointestinal cancer cells for activity evaluation. We found that compound 3 selectively inhibited MKN-45, whereas compounds 1 and 2 exhibited no significant inhibitory activity against the four cell lines. These findings suggested that 8,9-epi-chrodrimanins could serve as scaffold compounds for further structural modifications, potentially leading to the development of targeted therapies for gastric cancer.

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.

Isolation, structural determination, and antiviral activities of a novel alanine-conjugated polyketide from Talaromyces sp.

Antiviral agents are highly sought after. In this study, a novel alkylated decalin-type polyketide, alaspelunin, was isolated from the culture broth of the fungus Talaromyces speluncarum FMR 16671, and its structure was determined using spectroscopic analyses (1D/2D NMR and MS). The compound was condensed with alanine, and its absolute configuration was determined using Marfey's method. Furthermore, the antiviral activity of alaspelunin against various viruses was evaluated, and it was found to be effective against both severe acute respiratory syndrome coronavirus 2 and pseudorabies (Aujeszky's disease) virus, a pathogen affecting pigs. Our results suggest that this compound is a potential broad-spectrum antiviral agent.

Encapsulation of polyketide colorants in chitosan and maltodextrin microparticles.

This study aimed to encapsulate Talaromyces amestolkiae colorants in maltodextrin and chitosan microparticles using the spraydrying technique and to evaluate the biopolymers' capacities to protect the fungal colorant against temperature (65 °C) and extreme pH (2.0 and 13.0). The compact microparticles exhibited smooth or indented surfaces with internal diameters ranging between 2.58-4.69 µm and ζ ~ -26 mV. The encapsulation efficiencies were 86 % and 56 % for chitosan and maltodextrin microparticles, respectively. The shifted endothermic peaks of the free colorants indicated their physical stabilization into microparticles. The encapsulated colorants retained most of their absorbance (compared to the 0 h) even after 25 days at 65 °C. Contrary, the free colorant presented almost no absorbance after 1 day under the same conditions. Colorants in chitosan and maltodextrin matrices also partially maintained their colorimetric and fluorometric properties at acidic pH. However, only maltodextrin improved the resistance of the red colorant to alkaline environments. For the first time, the potential of polysaccharide-based microparticles to preserve polyketide colorants was demonstrated using 3D fluorescence. Therefore, this study demonstrated an alternative in developing functional products with natural color additives.

Secondary metabolites with fungicide potentials from the deep-sea seamount-derived fungus Talaromyces scorteus AS-242.

Marine natural products play an important role in biopesticides. Seven new secondary metabolites with different structural classes, including two cycloheptapeptides, scortide A (1) and scortide B (2), two 19-nor-diterpenoids, talascortene H (3) and talascortene I (4), two diterpenoid acids, talascortene J (5) and talascortene K (6), and one triterpenoid, talascortene L (7) were isolated and identified from the sea-anemone-derived endozoic fungus Talaromyces scorteus AS-242. Their structures were comprehensively assigned by spectroscopic data analysis, single-crystal X-ray diffraction, tandem mass spectrometry, and electronic circular dichroism (ECD) calculations. The result of the antimicrobial assay demonstrated that compounds 1 - 6 have inhibitory activity against several human, aquatic, and plant pathogens with minimum inhibitory concentration (MIC) values ranging from 1 to 64 µg/mL. Specially, compounds 2 and 4 showed significant activities against the pathogenic fungus Curvularia spicifera with the MIC value of 1 µg/mL, providing an experimental basis of 2 and 4 with the potential as lead compounds to be developed into biopesticides.

Antibacterial Polyketides from the Deep-Sea Cold-Seep-Derived Fungus Talaromyces sp. CS-258.

Thirty-two fungal polyketide derivatives, including eleven new compounds, namely (3R,5'R)-5-hydroxytalaroflavone (1), talaroisochromenols A-C (3, 5, and 11), (8R,9R,10aR)-5-hydroxyaltenuene (13), (8R,9R,10aS)-5-hydroxyaltenuene (14), (8R,9S,10aR)-5-hydroxyaltenuene (15), nemanecins D and E (25 and 26), 2,5-dimethyl-8-iodochromone (27), and talarofurolactone A (29), together with one new naturally occurring but previously synthesized metabolite, 6-hydroxy-4-methoxycoumarin (28), were isolated and identified from the deep-sea cold-seep-derived fungus Talaromyces sp. CS-258. Among them, racemic ((±)-11) or epimeric (13-15, 25, and 26) mixtures were successfully separated by chiral or gradient elution HPLC. Meanwhile, compound 27 represents a rarely reported naturally occurring iodinated compound. Their planar structures as well as absolute configurations were determined by extensive analysis via NMR, MS, single-crystal X-ray diffraction, Mosher's method, and ECD or NMR calculation (with DP4+ probability analysis). Possible biosynthetic routes of some isolated compounds, which are related to chromone or isochromone biosynthetic pathways, were put forward. The biological analysis results revealed that compounds 7, 9, 10, 18-22, 24, 30, and 31 showed broad-spectrum antibacterial activities against several human and aquatic pathogens with MIC ranges of 0.5-64 µg/mL.

Prenylated indole diketopiperazine alkaloids as phosphatase inhibitors from the marine-derived fungus Talaromyces purpureogenus.

Six previously undescribed prenylated indole diketopiperazine alkaloids, talaromyines A-F (1-6), were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data including NMR, HR-ESI-MS, and electronic circular dichroism calculations, together with chemical analysis of hydrolysates. Compounds 1-5 represent the first example of spirocyclic indole diketopiperazines biosynthesized from the condensation of L-tryptophan and L-alanine. Compounds 2 and 4-5 showed selective inhibitory activities against phosphatases TCPTP and MEG2 with IC50 value of 17.9-29.7 µM, respectively. Compounds 4-5 exhibited mild cytotoxic activities against two human cancer cell lines H1975 and HepG-2.

Development of dye-sensitized solar cells using pigment extracts produced by Talaromyces atroroseus GH2.

The identification of more efficient, clean, secure, and competitive energy supply is necessary to align with the needs of sustainable devices. For this reason, a study for developing innovative dye-sensitized solar cells (DSSCs) based on microbial pigments is reported starting from Talaromyces atroroseus GH2. The fungus was cultivated by fermentation and the extracellular pigment extract was characterized by HPLC-DAD-ESI-MS analyses. The most abundant compound among the 22 azaphilone-type pigments identified was represented by PP-O. The device's behavior was investigated in relation to electrolyte and pH for verifying the stability on time and the photovoltaic performance. Devices obtained were characterized by UV-vis measurements to verify the absorbance intensity and transmittance percentage. Moreover, photovoltaic parameters through photo-electrochemical measurements (I-V curves) and impedance characteristics by Electrochemical Impedance Spectroscopy (EIS) were determined. The best microbial device showed a short-circuit current density (Jsc) of 0.69 mA/cm2, an open-circuit photo-voltage (Voc) of 0.27 V and a Fill Factor (FF) of 0.60. Furthermore, the power conversion efficiency (PCE) of the device was 0.11%. Thus, the present study demonstrated the potential of microbial origin pigments for developing DSSCs.