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.

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.

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.

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.

Extending the Structural Diversity of Labdane Diterpenoids from Marine-Derived Fungus Talaromyces sp. HDN151403 Using Heterologous Expression.

Heterologous biosynthesis has become an effective means to activate fungal silent biosynthetic gene clusters (BGCs) and efficiently utilize fungal genetic resources. Herein, thirteen labdane diterpene derivatives, including five undescribed ones named talarobicins A-E (3-7), were discovered via heterologous expression of a silent BGC (labd) in Aspergillus nidulans. Their structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as electronic circular dichroism (ECD) calculations. These labdanes belong to four skeleton types, and talarobicin B (4) is the first 3,18-dinor-2,3:4,18-diseco-labdane diterpene with the cleavage of the C2-C3 bond in ring A and the decarboxylation at C-3 and C-18. Talarobicin B (4) represents the key intermediate in the biosynthesis of penioxalicin and compound 13. The combinatorial heterologous expression and feeding experiments revealed that the cytochrome P450 enzymes LabdC, LabdE, and LabdF were responsible for catalyzing various chemical reactions, such as oxidation, decarboxylation, and methylation. All of the compounds are noncytotoxic, and compounds 2 and 8 displayed inhibitory effects against methicillin-resistant coagulase-negative staphylococci (MRCNS) and Bacillus cereus.

Polyketides with potential bioactivities from the mangrove-derived fungus Talaromyces sp. WHUF0362.

Metabolites of microorganisms have long been considered as potential sources for drug discovery. In this study, five new depsidone derivatives, talaronins A-E (1-5) and three new xanthone derivatives, talaronins F-H (6-8), together with 16 known compounds (9-24), were isolated from the ethyl acetate extract of the mangrove-derived fungus Talaromyces species WHUF0362. The structures were elucidated by analysis of spectroscopic data and chemical methods including alkaline hydrolysis and Mosher's method. Compounds 1 and 2 each attached a dimethyl acetal group at the aromatic ring. A putative biogenetic relationship of the isolated metabolites was presented and suggested that the depsidones and the xanthones probably had the same biosynthetic precursors such as chrysophanol or rheochrysidin. The antimicrobial activity assay indicated that compounds 5, 9, 10, and 14 showed potent activity against Helicobacter pylori with minimum inhibitory concentration (MIC) values in the range of 2.42-36.04 µmol/L. While secalonic acid D (19) demonstrated significant antimicrobial activity against four strains of H. pylori with MIC values in the range of 0.20 to 1.57 µmol/L. Furthermore, secalonic acid D (19) exhibited cytotoxicity against cancer cell lines Bel-7402 and HCT-116 with IC50 values of 0.15 and 0.19 µmol/L, respectively. The structure-activity relationship of depsidone derivatives revealed that the presence of the lactone ring and the hydroxyl at C-10 was crucial to the antimicrobial activity against H. pylori. The depsidone derivatives are promising leads to inhibit H. pylori and provide an avenue for further development of novel antibiotics. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00170-5.

Beneficial effects of endophytic fungi inoculation on tanshinones and phenolic compounds of Salvia abrotanoides.

Objectives: Salvia abrotanoides is considered as a new source of tanshinone-producing plants in Iran. Symbiosis of endophytic fungi with their host plants is an effective tool to promote the growth and secondary metabolism of medicinal herbs. Therefore, using endophytic fungi as a biotic elicitor is a proper solution to increase the yield of plant products. Materials and Methods: In this study, some endophytic fungi were first isolated from the root of S. abrotanoides, then two of them (Penicillium canescens and Talaromyces sp.) were co-cultivated with the sterile seedling of S. abrotanoides in pot culture. After proving the colonization of these fungi in the root tissues by microscopic studies, their effects on the production of critical medicinal compounds such as tanshinones and phenolic acids were investigated in the vegetation stage (120 days). Results: Our results showed that the content of cryptotanshinone (Cry) and tanshinone IIA (T-IIA) in plants inoculated with P. canescens increased by 77.00% and 19.64%, respectively, compared with non-inoculated plants (control). The contents of mentioned compounds in plants inoculated with Talaromyces sp. increased by 50.00% and 23.00%, respectively. In this case, in plants inoculated with P. canescens, it was found that the level of caffeic acid, rosmarinic acid, and its PAL enzyme activity increased by 64.00%, 69.00%, and 50.00%, respectively, compared with the control. Conclusion: Endophytic fungi have specific modes of action and the ability to provide multiple benefits. Each of the two strains is a highly considerable microbial resource for the growth and accumulation of active compounds of S. abrotanoides.

Valorization of pineapple peel waste for fungal pigment production using Talaromyces albobiverticillius: Insights into antibacterial, antioxidant and textile dyeing properties.

The present study explores natural pigments as sustainable alternatives to synthetic textile dyes. Due to their therapeutic applications and easy production, fungal pigments have gained attention. However, data on pigment production using solid-state fermentation and optimization is limited. Milk whey was used to grow Talaromyces sp., followed by an evaluation of pigment production in solid and liquid media. Pineapple peels were used as a cost-effective substrate for pigment production, and a one-factor-at-a-time approach was used to enhance pigment production. Pineapple peel-based media produced 0.523 ± 0.231 mg/g of pigment after eight days of incubation. The crude pigment had promising antibacterial and significant antioxidant properties. The extraction fungal pigment's possible use as an eco-friendly textile dye was assessed through fabric dyeing experiments with different mordants. This work contributes to the valorization of agricultural waste and provides insight into using fungal pigments as sustainable alternatives to synthetic textile dyes.

Stoichiometric balance ratio of cellobiose and gentiobiose induces cellulase production in Talaromyces cellulolyticus.

BACKGROUND: The exact mechanism by which fungal strains sense insoluble cellulose is unknown, but research points to the importance of transglycosylation products generated by fungi during cellulose breakdown. Here, we used multi-omics approach to identify the transglycosylation metabolites and determine their function in cellulase induction in a model strain, Talaromyces cellulolyticus MTCC25456. RESULTS: Talaromyces sp. is a novel hypercellulolytic fungal strain. Based on genome scrutiny and biochemical analysis, we predicted the presence of cellulases on the surface of its spores. We performed metabolome analysis to show that these membrane-bound cellulases act on polysaccharides to form a mixture of disaccharides and their transglycosylated derivatives. Inevitably, a high correlation existed between metabolite data and the KEGG enrichment analysis of differentially expressed genes in the carbohydrate metabolic pathway. Analysis of the contribution of the transglycosylation product mixtures to cellulase induction revealed a 57% increase in total cellulase. Further research into the metabolites, using in vitro induction tests and response surface methodology, revealed that Talaromyces sp. produces cell wall-breaking enzymes in response to cellobiose and gentiobiose as a stimulant. Precisely, a 2.5:1 stoichiometric ratio of cellobiose to gentiobiose led to a 2.4-fold increase in cellulase synthesis. The application of the optimized inducers in cre knockout strain significantly increased the enzyme output. CONCLUSION: This is the first study on the objective evaluation and enhancement of cellulase production using optimized inducers. Inducer identification and genetic engineering boosted the cellulase production in the cellulolytic fungus Talaromyces sp.

Furanone, morpholinone and tetrahydrofuran derivatives from the marine-derived fungus Talaromyces sp. PSU-MF07.

Three new compounds including one furanone, one morpholinone and one tetrahydrofuran together with three known compounds were isolated from the broth extract of the marine-derived fungus Talaromyces sp. PSU-MF07. The structures of the isolated compounds were determined on the basis of spectroscopic methods. The relative configuration was assigned using NOEDIFF data whereas the absolute configurations were established by Mosher's method, specific rotations and electronic circular dichroism (ECD) data. Some isolated compounds were tested for antimicrobial activity. Only known penioxalicin exhibited weak antibacterial activity against methicillin-resistant Staphylococcus aureus SK1 with an MIC value of 200 µg/mL.

Spirocyclic polyketides from the marine fungus Talaromyces sp. CX11.

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.

Growth Stimulation, Phosphate Resolution, and Resistance to Fungal Pathogens of Some Endogenous Fungal Strains in the Rhizospheres of Medicinal Plants in Vietnam.

Endophytic fungi are recognized for their many potential applications in agriculture, such as supporting cropland expansion and increasing the yield and resistance of plants by creating antibiotics that inhibit the growth of pathogenic microorganisms. In addition, they can produce enzymes that break down hard-to-solubilize substances within soil, dissolve phosphates, fix nitrogen, reduce metals, and produce hormones that promote plant growth (auxin, cytokinin, and gibberellins) to keep crops healthy. In this report, three strains of endophytic fungi, namely, N1, N2, and N3, were isolated from the roots of Stevia rebaudiana (Bert.) Hemsl., Polyscias fruticosa, and Angelica dahurica in some localities in Vietnam. Through a screening process, it was found that they can produce high levels of indole acetic acid (IAA), resolve phosphates, and resist disease, and they were selected to as an alternative to chemical fertilizers to make probiotics in order to increase medicinal plant yields. The results show that the three strains of fungi have the ability to degrade phosphate to 341.90, 1498.46, and 390.79 ppm; the content of IAA produced in the culture medium reached 49.00, 52.35, and 33.34 ppm. Based on some morphological characteristics and an internal transcribed spacer gene sequence analysis of the fungal strains, N1, N2, and N3 were named Penicillium simplicissimum CN7, Talaromyces flavus BC1, and Trichoderma konilangbra DL3, respectively, which have the ability to inhibit the growth of pathogenic fungal strains, such as fungus C. gloeosporioides (CD1), fungus F. oxysporum, fungus L. theobromae N13, and N. dimidiatum. They grow significantly over a period of 5 to 6 days.

Diversity of Sclerotium rolfsii antagonist fungi isolated from soils of the rhizosphere of tomato crops and identification of some antifungal compounds.

Sclerotium rolfsii Sacc. the causative agent of white rot is one of the destructive pathogens of nightshade crops. In Côte d'Ivoire, this fungal pathogen constitutes a major constraint for the cultivation of tomato (Solanum lycopersicum) with 41.01% crop losses in humid forest areas. Controlling this fungus with synthetic chemicals can be effective, but harmful to human health and the environment. The use of biological control agents could be an alternative approach to control S. rolfsii. In this perspective, the objective of this work was to select fungi from the rhizosphere of tomato crops capable of inhibiting the growth of S. rolfsii. To do this, 153 fungi were isolated from the rhizosphere and from direct confrontation tests 10 fungi whose antagonistic power of S. rolfsii varied between 27 and 60% were selected. Molecular identification (ITS) of these antagonist fungi revealed that the isolates belonged to the genera Talaromyces sp. (n = 4), Trichoderma sp. (n = 3), Penicillium sp. (n = 2) and Clonostachys sp. (n = 1). Among these fungi, Talaromyces purpureogenus and Talaromyces assiutensis were able to diffuse compounds in agar capable of inhibiting the growth of S. rolfsii. The chemical study of these 2 fungi made it possible to identify mitorubrin and mitorubrinol produced by T. purpureogenus and spiculisporic acid produced by T. assiutensis. Mitorubrin and mitorubrinol had inhibitory activities of 100 and 70% at 10 mg/mL, respectively, whereas spiculisporic acid showed moderate inhibition of 38 at 20 mg/mL of the growth of S. rolfsii; however, its abundant production by the fungus could be an advantage in the control of this phytopathogen. Isolated from the same biotope as S. rolfsii, T. purpureogenus and T. assiutensis represent favorable candidates for the biological control against S. rolfsii.

New Antibacterial Secondary Metabolites from a Marine-Derived Talaromyces sp. Strain BTBU20213036.

New polyketide-derived oligophenalenone dimers, bacillisporins K and L (1 and 2) and xanthoradone dimer rugulosin D (3), together with four known compounds, bacillisporin B (4), macrosporusone D (5), rugulosin A and penicillide (6 and 7), were isolated from the marine-derived fungus Talaromyces sp. BTBU20213036. Their structures were determined by detailed analysis of HRESIMS, 1D and 2D NMR data, and the absolute configurations were determined on the basis of calculated and experimental electronic circular dichroism (ECD). The antibacterial and antifungal activities of these compounds were tested against Gram-positive-Staphylococcus aureus, Gram-negative-Escherichia coli, and fungal strain-Candida albicans. These compounds showed potential inhibitory effects against S. aureus with minimum inhibitory concentrations ranging from 0.195 to 100 µg/mL.

Talaromydien a and talaroisocoumarin A, new metabolites from the marine-sourced fungus Talaromyces sp. ZZ1616.

New talaromydien A (1) and talaroisocoumarin A (2), together with nine known compounds (3 - 11), were isolated from a culture of the marine-derived Talaromyces sp. ZZ1616 in potato dextrose broth medium. Structures of the new compounds were elucidated based on their HRESIMS data, NMR spectroscopic analyses, the modified Mosher's method, ECD, 13C NMR and optical rotation calculations. Talaroisocoumarin A showed antimicrobial activities with MIC values of 36.0 µg/mL against methicillin-resistant Staphylococcus aureus, 32.0 µg/mL against Escherichia coli, and 26.0 µg/mL against Candida albicans.

Talaromyces stipitatus, a novel agent causing superficial mycosis in a diabetic patient from North India.

Among millions of reported fungal species, only a few hundred species are capable of causing diseases in humans and animals that range from superficial to life-threatening infections. Both immunocompetent as well as immunocompromised patients with underlying diseases, such as AIDS, diabetes, etc., are at higher risk of acquiring fungal infections. Superficial mycoses invade the stratum corneum and the outermost layers of the skin. The aim of the present study was to study clinical symptoms, isolate and identify the causal agent in the investigated patient along with sharing insights achieved through reviewing the literature. Direct microscopy, cultural, microscopic, and molecular characterization was done to identify the recovered causal agent. Herein, we report a case of superficial mycosis that affected the left foot of a 65-year-old diabetic male who was a farmer by occupation from district Jammu, Jammu and Kashmir, India. The pathogenic fungal species was identified as Talaromyces stipitatus. To the best of our knowledge, there are no reports on T. stipitatus as a causal agent of skin infection so far. Thus, the causal agent described in the research communication constitutes a new addition to the list of pathogenic non-dermatophytes associated superficially with human skin. In-vitro antifungal activity revealed fluconazole as the most effective antifungal agent against the causal agent.

Secondary Metabolites with α-Glucosidase Inhibitory Activity from Mangrove Endophytic Fungus Talaromyces sp. CY-3.

Eight new compounds, including two sambutoxin derivatives (1-2), two highly oxygenated cyclopentenones (7-8), four highly oxygenated cyclohexenones (9-12), together with four known sambutoxin derivatives (3-6), were isolated from semimangrove endophytic fungus Talaromyces sp. CY-3, under the guidance of molecular networking. The structures of new isolates were elucidated by analysis of detailed spectroscopic data, ECD spectra, chemical hydrolysis, 13C NMR calculation, and DP4+ analysis. In bioassays, compounds 1-5 displayed better α-glucosidase inhibitory activity than the positive control 1-deoxynojirimycin (IC50 = 80.8 ± 0.3 µM), and the IC50 value was in the range of 12.6 ± 0.9 to 57.3 ± 1.3 µM.

Identification of a new Talaromyces strain DYM25 isolated from the Yap Trench as a biocontrol agent against Fusarium wilt of cucumber.

Fusarium equiseti is a pathogenic fungus of plant root rot, and there are few studies on the biocontrol strains of plant wilt caused by F. equiseti. Hence, we conducted a screening and antimicrobial characterization study of marine-origin biocontrol fungi from water samples of the Yap Trench. A new Talaromyces strain DYM25 was screened from water samples of the Yap Trench in the western Pacific Ocean, and its potential as a biocontrol agent against Fusarium wilt of cucumber was studied. 18S rRNA and ITS gene sequencing verified that strain DYM25 belongs to the genus Talaromyces. The growth of F. equiseti was inhibited by strain DYM25 through the antibiosis effect. A preliminary test was first conducted to examine the bioactive stability of filtered DYM25 broth against F. equiseti under various conditions, including high temperature, UV light, alkaline environment, and the presence of metal ions, which indicated its potential as a bio-control agent. The results of the pot experiment showed that F. equiseti caused cucumber wilt, which could be mitigated using the fermentation broth of strain DYM25 (52.9 %). On the other hand, the alkaloid chromogenic reaction showed that the alkaloid salts present in the crude n-butanol extracts were most likely the major components that might have an antimicrobial effect. Therefore, Talaromyces sp. DYM25 represents a new species that can be used as a novel biocontrol agent against cucumber wilt.

Combined microbial degradation of crude oil under alkaline conditions by Acinetobacter baumannii and Talaromyces sp.

The purpose of this work was to study the biodegradation of crude oil under alkaline condition by defined co-culture of Acinetobacter baumannii and Talaromyces sp. The n-alkanes in crude oil could be completely degraded by bacteria and fungi with the ratio of 1:1 at pH 9 in 14 d water simulation experiment. Meanwhile, the total degradation rate of crude oil could reach 80%. Fungi had stronger ability to degrade n-alkanes, while bacteria could better degrade other components such as aromatics and branched alkanes. The two strains were both capable of producing a small amount of biosurfactant. High cell viability was the main factor for strains to exert high degradation ability in alkaline environment. It was preliminarily verified that bacteria and fungi rely on the differences of enzyme systems to achieve synergy in the degradation process. These results indicated that the defined co-culture had great potential for bioremediation in alkaline soils.

Two new bioactive polyphenols from the soft coral-derived fungus Talaromyces sp. SCSIO 041201.

Two new polyphenols, talaversatilis A (1) and B (2), together with fifteen known compounds (3-17) were isolated from the extract of the culture broth of a soft coral-derived fungus Talaromyces sp. SCSIO 041201. The structures of these compounds were elucidated by the extensive analyses of spectroscopic data and by comparison with the reported literature. Antifouling and antibacterial activities of all purified compounds were tested and evaluated. Compounds 5 and 6 showed antifouling activity towards Bugula neritina larva, with LC50 values of 3.86 µg/mL and 3.05 µg/mL, respectively. Compounds 7, 8, 10 and 13 exhibited significant antibacterial activities against E. coli, MRSA, S. aureus and E. faecalis, with MIC values ranging from 0.45 to 15.6 µg/mL.