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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 IC 50 values of 27.19, 41.55, 25.23, and 24.71 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests associated with this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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 IC 50 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.

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 1 H and 13 C 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 IC 50 values ranging from 1.6 to 8.6 μ M. Additionally, compounds 9 and 18 exhibited moderate inhibition against Con A-induced T lymphocyte proliferation with IC 50 values of 9.3 and 2.6 μ M, respectively.

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.

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 IC 50 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.

Three new indole alkaloids, named talatensindoids A-C (1-3), together with two known biogenetically related indole alkaloids tryptamine (4) and L-tryptophan (5) were isolated from the Talaromyces assiutensis JTY2 based on the guidance of OSMAC approach. The structures of these indole alkaloids were determined by comprehensive spectroscopic analyses. The absolute configuration of 3 was confirmed by X-ray crystallographic analysis. Compound 1 represent the rare example of a chlorine-substituted indole alkaloid from natural products. The inhibitory activity of compounds 1-5 against two phytopathogenic fungi and three phytopathogenic bacteria was evaluated. Compound 1 exhibited broad spectrum antibacterial activities., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

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., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

The soil-derived fungus Talaromyces thailandensis PSU-SPSF059 produced one new vermistatin derivative, talarostatin, and seven known compounds including two vermistatins, two chrodrimanins, two diphenyl ethers and one penicillide derivative. Extensive spectroscopic analysis was performed to identify their structures. The absolute configuration of talarostatin was determined by comparing the experimental and calculated electronic circular dichroism data. The antimicrobial and cytotoxic activities of the isolated secondary metabolites were also evaluated.

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 IC 50 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-β1-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.

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 K d and T 1/2 values. Furthermore, the hydrolytic activity of chitinase was enhanced after immobilization on UiO-66, with an increase in the V max and a decrease in the K m 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 MIC 50 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., (© 2024. The Author(s).)

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 IC 50 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.

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 β- 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 Bs PdaC. 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.

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 IC 50 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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 IC 50 value from 4.59 to 21.60 μM.

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.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Alkaloids with a phenylhydrazone architecture are rarely found in nature. Four unusual phenylhydrazone alkaloids named talarohydrazones A-D ( 1 - 4 ) were isolated from the deep-sea cold seep derived fungus Talaromyces amestolkiae HDN21-0307 using the one strain-many compounds (OSMAC) approach and MS/MS-based molecular networking (MN) combined with network annotation propagation (NAP) and the unsupervised substructure annotation method MS2LDA. Their structures were elucidated by spectroscopic data analysis, single-crystal X-ray diffraction, and quantum chemical calculations. Talarohydrazone A ( 1 ) possessed an unusual skeleton combining 2,4-pyridinedione and phenylhydrazone. Talarohydrazone B ( 2 ) represents the first natural phenylhydrazone-bearing azadophilone. Bioactivity evaluation revealed that compound 1 exhibited cytotoxic activity against NCI-H446 cells with an IC 50 value of 4.1 μM. In addition, compound 1 displayed weak antibacterial activity toward Staphylococcus aureus with an MIC value of 32 μg/mL.

Oxabornyl polyenes represent a unique group of polyketides characterized by a central polyene core flanked by a conserved oxabornyl moiety and a structurally diverse oxygen heterocyclic ring. They are widely distributed in fungi and possess a variety of biological activities. Due to the significant spatial separation between the two stereogenic ring systems, it is difficult to establish their overall relative configurations. Here, we isolated three oxabornyl polyenes, prugosenes A1-A3 ( 1 - 3 ), from Talaromyces sp. JNU18266-01. Although these compounds were first reported from Penicillium rugulosum , their overall relative and absolute configurations remained unassigned. By employing ozonolysis in combination with ECD calculations, we were able to establish their absolute configurations, and additionally obtained seven new chemical derivatives ( 4 - 10 ). Notably, through NMR data analysis and quantum chemical calculations, we achieved the structural revision of prugosene A2. Furthermore, prugosenes A1-A3 exhibited potent antiviral activity against the respiratory syncytial virus, with compound 1 displaying an IC 50 value of 6.3 μM. Our study thus provides a valuable reference for absolute configuration assignment of oxabornyl polyene compounds.

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 .

Ten new compounds, including three pairs of diarylcyclopentenone enantiomers (±) talaromycesins A-C (1-3) and four biphenyl derivatives talaromycesins D-G (4-7), along with four known compounds (8-11), were isolated from the fungus Talaromyces adpressus. Their structures were determined by analyses of extensive NMR spectroscopic and HRESIMS data, and their absolute configurations were elucidated by the dimolybdenum tetraacetate [Mo 2 (AcO) 4 ]-induced ECD spectra, X-ray crystallographic studies, and ECD calculations. These new compounds were evaluated for their immunosuppressive activities for the first time, and compound 7 probably exerted liver-protective and anti-inflammatory effects on Con A-induced AIH by decreasing the levels of inflammatory cytokines, modulating immune homeostasis, and decreasing hepatocyte apoptosis, which may become a potential drug for the treatment of autoimmune diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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).

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/cm 2 , 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., (© 2024. The Author(s).)

Thirty-two fungal polyketide derivatives, including eleven new compounds, namely (3 R ,5' R )-5-hydroxytalaroflavone ( 1 ), talaroisochromenols A-C ( 3 , 5 , and 11 ), (8 R ,9 R ,10a R )-5-hydroxyaltenuene ( 13 ), (8 R ,9 R ,10a S )-5-hydroxyaltenuene ( 14 ), (8 R ,9 S ,10a R )-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.

Three new cyclic heptapeptides, talaromides A-C ( 1 - 3 ), were isolated from cultures produced by the fungus Talaromyces siglerae (Ascomycota), isolated from an unidentified sponge. The structures, featuring an unusual proline-anthranilic moiety, were elucidated by analysis of spectroscopic data and chemical transformations, including the advanced Marfey's method and GITC derivatization. Talaromides A and B inhibited migration activity against PANC-1 human pancreatic cancer cells without significant cytotoxicity.

We report on the use of n itric o xide- me diated t ranscriptional a ctivation (NOMETA) as an innovative means to detect and access new classes of microbial natural products encoded within silent biosynthetic gene clusters. A small library of termite nest- and mangrove-derived fungi and actinomyces was subjected to cultivation profiling using a miniaturized 24-well format approach (MATRIX) in the presence and absence of nitric oxide, with the resulting metabolomes subjected to comparative chemical analysis using UPLC-DAD and GNPS molecular networking. This strategy prompted study of Talaromyces sp. CMB-TN6F and Coccidiodes sp. CMB-TN39F, leading to discovery of the triterpene glycoside pullenvalenes A-D ( 1 - 4 ), featuring an unprecedented triterpene carbon skeleton and rare 6- O -methyl- N -acetyl-d-glucosaminyl glycoside residues. Structure elucidation of 1 - 4 was achieved by a combination of detailed spectroscopic analysis, chemical degradation, derivatization and synthesis, and biosynthetic considerations.

Three novel meroterpenoids, taladrimanins B-D ( 1 - 3 ), were isolated from the marine-derived fungus Talaromyces sp. M27416, alongside three biogenetically related compounds ( 4 - 6 ). We delineated taladrimanin B's ( 1 ) structure using HRESIMS and NMR, confirmed its configuration via quantum chemical NMR analysis and DP4+ methodology, and verified it through X-ray crystallography. ECD calculations determined the absolute configuration of compound 1 , while comparative NMR and ECD analyses elucidated the absolute configurations of 2 and 3 . These compounds are drimane-type meroterpenoids with a C10 polyketide unit (8 R -configuration). We proposed a biosynthetic pathway and noted that compound 1 showed cytotoxic activity against MKN-45 and 5637 cell lines and selective antibacterial effects against Staphylococcus aureus CICC 10384.

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 IC 50 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., Competing Interests: Declaration of competing interest All authors declare that they have no financial and personal relationships with other people or organizations that can inappropriately influence this work. There is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Talcarpones A (1) and B (2) are rare bisnaphthazarin derivatives produced by Talaromyces johnpittii (ex-type strain MST-FP2594), a newly discovered Australian fungus, which is formally described and named herein. The talcarpones were isolated along with the previously reported monomeric naphthoquinone, aureoquinone (3), suggesting a biosynthetic link between these metabolites. Talcarpone A is a lower homologue of hybocarpone (4), which was first isolated from a mycobiont of the lichen Lecanora hybocarpa. The structures of 1 and 2 were elucidated by detailed spectroscopic analysis, molecular modelling and comparison with literature data. Talcarpones 1 and 2 exhibited moderate antifungal activity (MIC 0.78-3.1 µg ml -1 ) and weak activity against Gram-positive bacteria (MIC 13-25 µg ml -1 ). The talcarpones also demonstrated noteworthy chemical reactivities, with 2 converting rapidly to 1, which in turn converted slowly to the highly coloured 3. These post-biosynthetic reactions point to a potential ecological role for the talcarpones in providing ongoing (slow-release) physicochemical protection for T. johnpittii against solar irradiation., (© 2023. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Five pairs of undescribed enantiomeric α-pyrone derivatives (±)-adprepyrones A-E (±1-±5), together with an unreported congener adprepyrone F (6), and 6-[(E)-3-Hydroxyprop-1-enyl]-4-methoxy-5-methyl-2-pyrone (7), recently reported as synthetic compound, were isolated from the fungus Talaromyces adpressus. Their structures with absolute configurations were elucidated by HRESIMS, 1D and 2D NMR, electronic circular dichroism calculations, and single-crystal X-ray diffraction analyses. (±)-Adprepyrone A (±1) possesses an unreported carbon skeleton formed by the fusion of an α-pyrone derivative with nicotinamide. Compounds (+)-2, (±)-4, (±)-5, and 7 showed moderate inhibitory activity against concanavalin A (ConA)-induced T lymphocyte proliferation with IC 50 values ranging from 8.9 to 19.8 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023. Published by Elsevier Ltd.)

Two new compounds, compounds 1 and 2 , were obtained from the culture of a marine-derived fungus Talaromyces sp. MCCC 3A01752, together with 13 known compounds ( 3 - 15 ). Their structures were elucidated based on detailed analysis of NMR, HRESIMS, ECD spectra and OR value. Compound 1 exhibited antibacterial potential against Staphylococcus aureus with a MIC value of 100 μM and cytotoxic activity against gastric cancer cell line MKN1 with a IC 50 value of 78.0 μM.

Two new nonadride derivatives, namely, talarodrides G and H (1 and 2), and one new depsidone derivative, botryorhodine K (3), together with a known nonadride analogue (4), were characterized from the Magellan Seamount-derived fungus Talaromyces scorteus AS-242. Their structures were established by detailed interpretation of NMR spectroscopic and mass spectrometry data analysis. X-ray crystallographic analysis of compounds 1 and 3 confirmed their structures and absolute configurations, representing the first characterized crystal structure of a nonadride-type polyketide. The isolated compounds exhibited potent antimicrobial activities against the pathogenic bacterium MRSA and V. parahaemolyticus and pathogenic fungi C. gloeosporioides, F. oxysporum, and F. proliferatum, with MIC values ranging from 1 to 64 μg ml -1 ., (© 2023. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

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 IC 50 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 IC 50 values of 117 nM and 212 nM, respectively, and displayed significant antitumour effects in A549 cells by inhibiting the PI3K-Akt-mTOR signalling pathway.

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.

In recent years, there has been a lot of buzz about the possibilities of marine microflora as a source of new therapeutic drugs. The strong anti-tumor potency of compounds found in marine resources reflects the ocean's enormous potential as a source of anticancer therapeutics. In this present investigation, an ambuic acid derivative anticancer compound was isolated from Talaromyces flavus, and its cytotoxicity and apoptosis induction potential were analyzed. T. flavus was identified through morphological and molecular analysis. The various organic solvent extracts of T. flavus grown on different growth mediums were evaluated for cytotoxicity on different cancer cell lines. The potent cytotoxicity was shown in the ethyl acetate extract of a fungal culture grown in the M1-D medium for 21 days. Furthermore, the anticancer compound was identified using preparative thin layer chromatography, followed by its purification in significant proportions using column chromatography. The spectroscopic and chromatographic analysis revealed that the structure of the purified molecules was an ambuic acid derivative. The ambuic acid derivative compound showed potent cytotoxicity on MDA-MB-231 (breast cancer cells) with an IC 50 value of 26 μM and induced apoptosis in the MDA-MB-231 cells in a time-dependent and reactive oxygen species-independent manner., (© 2023 John Wiley & Sons Ltd.)

Chemical analysis of cultures of a Queensland mud dauber wasp nest-derived fungus, Talaromyces sp. CMB-MW102, yielded the known dimeric oxaphenalenone duclauxin ( 1 ) along with a family of new 1-deoxy-d-glucosamine adducts, glyclauxins A-E ( 2 - 6 ). Despite 1D NMR spectra of 2 - 6 being compromised by broadening of selected resonances, structures inclusive of absolute configuration were assigned on the basis of detailed spectroscopic analysis and biogenetic considerations, as well as biomimetic semisynthesis and chemical interconversion. For example, exposure of duclauxin ( 1 ) to synthetic 1-deoxy-d-glucosamine yielded glyclauxin B ( 3 ), while on handling and storage, glyclauxins C ( 4 ) and D ( 5 ) (bearing a 7-OMe moiety) proved chemically labile and underwent quantitative transformation to glyclauxins B ( 3 ) and A ( 2 ), respectively. These latter observations on chemical reactivity and stability informed a proposed biogenetic relationship linking all known members of the extended duclauxin family. Notwithstanding their potential status as artifacts, the detection of glyclauxins B ( 3 ) and A ( 2 ) in a fresh CMB-MW102 culture extract confirmed their natural product status.

An undescribed hybrid phenalenone dimer, talaropinophilone ( 3 ), an unreported azaphilone, 7- epi -pinazaphilone B ( 4 ), an unreported phthalide dimer, talaropinophilide ( 6 ), and an undescribed 9 R ,15 S -dihydroxy-ergosta-4,6,8 (14)-tetraen-3-one ( 7 ) were isolated together with the previously reported bacillisporins A ( 1 ) and B ( 2 ), an azaphilone derivative, Sch 1385568 ( 5 ), 1-deoxyrubralactone ( 8 ), acetylquestinol ( 9 ), piniterpenoid D ( 10 ) and 3,5-dihydroxy-4-methylphthalaldehydic acid ( 11 ) from the ethyl acetate extract of the culture of a marine sponge-derived fungus, Talaromyces pinophilus KUFA 1767. The structures of the undescribed compounds were elucidated by 1D and 2D NMR as well as high-resolution mass spectral analyses. The absolute configuration of C-9' of 1 and 2 was revised to be 9' S using the coupling constant value between C-8' and C-9' and was confirmed by ROESY correlations in the case of 2 . The absolute configurations of the stereogenic carbons in 7 and 8 were established by X-ray crystallographic analysis. Compounds 1 , 2 , 4 - 8 , 10 and 11 were tested for antibacterial activity against four reference strains, viz. two Gram-positive ( Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212) and two Gram-negative ( Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853), as well as three multidrug-resistant strains, viz. an extended-spectrum β-lactamase (ESBL)-producing E. coli , a methicillin-resistant S. aureus (MRSA) and a vancomycin-resistant E. faecalis (VRE). However, only 1 and 2 exhibited significant antibacterial activity against both S. aureus ATCC 29213 and MRSA. Moreover, 1 and 2 also significantly inhibited biofilm formation in S. aureus ATCC 29213 at both MIC and 2xMIC concentrations.

Amestolkins A ( 1 ) and B ( 2 ), two previously undescribed phthalides sharing the same planar structure of (1, 5-dihydroxyhexyl)-7-hydroxyisobenzofuran-1(3 H )-one were isolated from Talaromyces amestolkiae . Their absolute configurations were elucidated by comprehensive analyses of spectroscopic evidences in high-resolution electrospray mass spectra (HRESIMS) and nuclear magnetic resonance (NMR) combined with electronic circular dichroism (ECD) and NMR calculations. 1 and 2 showed anti-neuroinflammatory activity by inhibiting the gene expressions of proinflammatory factors including C-C motif chemokine ligand 2 (CCL-2), tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), as well as attenuating the excretion of inducible nitric oxide synthase (iNOS) in BV-2 microglial cells at the concentration of 30 μM.

Vanitaracin A, an anti-hepatitis B virus polyketide, has been previously isolated from Talaromyces sp. In the present study, we searched for novel compounds in the culture broth obtained from a vanitaracin A-producing fungus under various conditions. Three novel compounds (vanitaracin C, vanitaraphilone A, and 2-hydroxy-4-(hydroxymethyl)-6-methylbenzaldehyde) were isolated, and their structures were determined using spectroscopic methods (1D/2D NMR and MS). In addition, the antiviral spectrum of vanitaracin A was examined by measuring its antiviral activities against rabies virus, Borna disease virus 1, and bovine leukemia virus. This compound exhibited antiviral activity against bovine leukemia virus, which is the causative agent of enzootic bovine leukosis. The anti-bovine leukemia virus effects of other compounds isolated from the vanitaracin A-producing fungus, namely, vanitaracins B and C, vanitaraphilone A, and 2-hydroxy-4-(hydroxymethyl)-6-methylbenzaldehyde, were also evaluated. Vanitaracin B, vanitaraphilone A and 2-hydroxy-4-(hydroxymethyl)-6-methylbenzaldehyde were also found to exhibit activity against bovine leukemia virus. These findings reveal the broad-spectrum antiviral activity of the vanitaracin scaffold and suggest several candidates for the development of anti-bovine leukemia virus drugs., (© 2022. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Three new spirocyclic polyketides, talaromyacins A - C, were identified from the endophytic fungus Talaromyces sp. CX11. Their structures including absolute configurations were determined by extensive spectroscopic analysis, Snatzke's method and quantum chemical calculations. Talaromyacin A is identical to the known sequoiamonascin A, for which a structural revision is required., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We report the discovery of talaropeptins A ( 1 ) and B ( 2 ), tripeptides with an unusual 5/6/5 heterocyclic scaffold and an N - trans -cinnamoyl moiety, which were identified from the marine-derived fungus Talaromyces purpureogenus CX11. A bioinformatic analysis of the genome of T. purpureogenus CX11 and gene inactivation revealed that the biosynthesis of talaropeptins involves a nonribosomal peptide synthase gene cluster. Their chemical structures were elucidated using a combination of 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configurations of 1 and 2 were established by electronic circular dichroism calculations and Marfey's method. The plausible biosynthesis of 1 and 2 is also proposed on the basis of gene deletion, substrate feeding, and heterologous expression. Compounds 1 and 2 showed moderate antifungal activity against phytopathogenic fungus Fusarium oxysporum with MIC values of 12.5 and 25 μg/mL, respectively.

Three new compounds including a meroterpenoid ( 1 ) and two isocoumarins ( 8 and 9 ), together with thirteen known compounds ( 2-7 , 10-16 ) were isolated from the metabolites of Talaromyces amestolkiae MST1-15. Their structures were identified by a combination of spectroscopic analysis. The absolute configuration of compound 1 was elucidated on the basis of experimental and electronic circular dichroism calculation, and compounds 8 and 9 were determined by Mo 2 (OAc) 4 -induced circular dichroism experiments. Compounds 7-16 showed weak antibacterial activities against Stenotrophomonas maltophilia with MIC values ranging from 128 to 512 μg/mL (MICs of ceftriaxone sodium and levofloxacin were 128 and 0.25 μg/mL, respectively).

Talasterone A (1), an unprecedented 6/6/5 tricyclic 13(14 → 8)abeo-8,14-seco-ergostane steroid, together with two known congeners dankasterone B (2) and (14β,22E)-9,14-dihydroxyergosta-4,7,22-triene-3,6-dione (3), were characterized from Talaromyces adpressus. The structure of 1 with absolute configuration was elucidated based on NMR spectroscopic data and ECD calculation. Compound 2 belongs to a class of unconventional 13(14 → 8)abeo-ergostanes, which have been renewed via the 1,2-migration of C-13-C-14 bond to C-8. In addition, compound 1 represents the first example of ergostane with a tricyclic 13(14 → 8)abeo-8,14-seco-ergostane skeleton. The proposed biosynthetic pathway was established with the support of the coisolation of the known congeners from the producing organism. It is especially noteworthy that compound 1 exhibited potent anti-inflammatory activity with an IC 50 value of 8.73 ± 0.66 μM, inhibiting the NF-κB pathway and thus reducing the production of proinflammatory cytokines., (Copyright © 2022. Published by Elsevier Inc.)

(+)-Talarolactone C (1), Talarolactone A (2), Talarolactone B (3, sulfoxide derivative), and Talarolactone D (4, sulfone derivative) were isolated from Talaromyces sp. which was cultured in rice medium with sodium butyrate. The structures of talarolactone analogs above were characterized by a combination of spectroscopic, X-ray crystallographic, and computational methods. These talarolactones and Talarolactone A sodium (5) with the same carbon skeleton showed different fluorescence characteristics., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Five new aromatic polyketides, including a unique benzofuran derivative, talarominine A ( 1 ), and four chromone analogs talamins A-D ( 2 - 5 ), along with one known related metabolite, 5-hydroxy-7-methoxy-2,3-dimethylchromone ( 6 ), were isolated and identified from the Talaromyces minioluteus CS-138, an endozoic fungus obtained from the deep-sea cold seep mussel Gigantidas platifrons . Their chemical structures were elucidated by detailed analysis of their NMR spectra, HRESIMS and X-ray crystallographic data, and by comparison with literature data as well. The antibacterial and DPPH scavenging activities of compounds 1 - 6 were evaluated. Compounds 1 - 3 showed inhibitory activity against some of the tested bacteria whereas compounds 2 and 5 showed potent DPPH radical scavenging activities, which were better than that of the positive control butylated hydroxytoluene (BHT). This work is likely the first report on marine natural products of mussel-derived fungus living in cold seep environments.

One new lactone derivative helicascolide F ( 1 ), one new pyrrolidine derivative talaromydine ( 2 ), along with six known compounds ( 3 - 8 ) were isolated from the fungus Talaromyces assiutensis JTY2. The structure of the new compounds 1 and 2 was determined by 1D and 2D NMR as well as by HRESIMS. The inhibitory activity of all compounds against six phytopathogenic fungi and three cancer cell lines was evaluated.

Talaromynoids A-E ( 1 - 5 ), five new fusicoccane diterpenoids, were obtained from the endophytic fungus Talaromyces sp. DC-26, which was isolated from a wild leech. Talaromynoid A ( 1 ) represents the first fusicoccane diterpenoid bearing an unexpected 5-7-5 tricyclic ring system, which is possibly derived from normal 5-8-5 ones by ring contraction. Talaromynoid E ( 5 ) is characterized by an unusual oxygen bridge between C-1 and C-8 that establishes the eight-membered ring B to be a 9-oxo-bicyclo[3.3.1]nonane. Structures of 1 - 5 with absolute configurations were determined by extensive NMR spectral analyses, electronic circular dichroism (ECD) calculations, X-ray diffraction analyses, and acid hydrolysis.

Six new isocoumarin derivative talaromarins A-F ( 1 - 6 ), along with 17 known analogues ( 7 - 23 ), were isolated from the mangrove-derived fungus Talaromyces flavus (Eurotiales: Trichocomaceae) TGGP35. Their structures were identified by detailed IR, UV, 1D/2D NMR and HR-ESI-MS spectra. The absolute configurations of new compounds were determined by the modified Mosher's method and a comparison of their CD spectra with dihydroisocoumarins described in the literature. The antioxidant, antibacterial, anti-phytopathogenic and inhibitory activity against α-glucosidase of all the isolated compounds were tested. Compounds 6 - 1 1 , 17 - 19 and 21 - 22 showed similar or better antioxidant activity than the IC 50 values ranging from 0.009 to 0.27 mM, compared with the positive control trolox (IC 50 = 0.29 mM). Compounds 10 , 18 , 21 and 23 exhibited strong inhibitory activities against α-glucosidase with IC 50 values ranging from 0.10 to 0.62 mM, while the positive control acarbose had an IC 50 value of 0.5 mM. All compounds showed no antibacterial or anti-phytopathogenic activity at the concentrations of 50 μg/mL and 1 mg/mL, respectively. These results indicated that isocoumarins will be useful to developing antioxidants and as diabetes control agents.

A new meroterpenoid, taladrimanin A (1), was isolated from a marine-derived fungus Talaromyces sp. HM6-1-1, together with eleven biogenetically related compounds (2-12). A plausible biosynthetic pathway for the meroterpenoids (1-4) was proposed. The planar structure of 1 was assigned by HRESIMS and NMR. Its relative configuration was established by quantum chemical NMR calculation of two possible isomers and analyzed by DP4 + method. Finally, X-ray diffraction unambiguously confirmed the relative configuration and revealed the absolute configuration of compound 1. 2-12 were assigned by comparing their NMR data with those reported in the literature. 1 was the first drimane-type meroterpenoid with a C10 polyketide unit bearing an 8R-configuration. In the bioactive assay, 1 exhibited antitumor activity against gastric cancer cells MGC803 and MKN28; it also inhibited the colony formation and induced apoptosis in MGC803 cells both in a concentration-dependent manner. Additionally, 1 displayed selective antibacterial activity against Staphylococcus aureus 6538P, and low activities towards strains of Vibrio parahaemolyticus and Escherichia coli in this study. KEY POINTS: • Twelve compounds were obtained from Talaromyces sp., including four meroterpenoids, one of which was new. • The new compound taladrimanin A (1) inhibits the growth of gastric cancer cells MGC803 and MKN28 as well as the pathogenic bacteria Staphylococcus aureus 6538P. • The biosynthetic pathway of the meroterpenoids was proposed., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Two new decalin derivatives named fusarielins O (1) and P (2), together with seven known compounds (3-9) were isolated from the crude extract of the marine-derived fungus Talaromyces sp. The planar structures of the new compounds were elucidated by comprehensive spectroscopic analyses of NMR and HR-ESI-MS. The absolute configuration of 1 was assigned by Snatzke's method and comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1-9 were evaluated for their cytotoxic activities against three tumor cell lines and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)