Search Results (18)

Villosiclava virens (anamorph: Ustilaginoidea virens), the causal fungal pathogen of rice false smut, has been found to produce various secondary metabolites. The albino strain LN02 is a natural albino phenotype mutant of V. virens due to its inability to produce ustilaginoidins. The fermentation of V. virens LN02 was performed in solid rice medium to obtain fungal cultures, which were chemically investigated. After removing the known metabolites, two new dimeric sorbicillinoids, namely ustisorbicillinols G (1) and H (2), were isolated from the ethyl acetate extract. Their structures were elucidated using spectroscopic data analyses and quantum chemical calculations. Compounds 1 and 2 displayed antibacterial activity towards Ralstonia solanacearum, Agrobacterium tumefaciens and Bacillus subtilis, with median inhibitory concentration (IC₅₀) values of 19.76–25.43 μg/mL for 1 and 25.35–45.48 μg/mL for 2. The discovery of new sorbicillinoids will increase the diversity of the secondary metabolites of V. virens and provide candidates for the creation of new antimicrobials as well. Full article

Five new natural products, including two sorbicillinoids (1–2), one indolinone alkaloid (10), one tetracyclic steroid (11), and one α-pyrone derivative (14), were identified from the endophytic Penicillium sp. NX-S-6, together with thirteen known natural products. The structures of new compounds were unambiguously elucidated by comprehensive spectroscopic analyses (NMR, MS), as well as electronic circular dichroism (ECD) calculation. Notably, quinosorbicillinol (1) was identified as a rare hybrid sorbicillinoid incorporating a quinolone moiety, representing a unique structural scaffold in this natural product class. Biological evaluation revealed that Compounds 1, 4 and 8 potently inhibited the production of nitric oxide and interleukin 6 in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Mechanistic studies furthermore demonstrated that Compounds 4 and 8 effectively suppressed interleukin-1β secretion in LPS-induced immortalized mouse bone marrow-derived macrophages (iBMDMs) by blocking NLRP3 inflammasome activation. This inhibition was attributed to their ability to disrupt the assembly of the NLRP3-caspase-1 complex, a key event in the pathogenesis of inflammatory disorders. These findings not only expand the structural diversity of endophyte-derived natural products but also highlight their potential as lead compounds for developing anti-inflammatory therapeutics targeting the NLRP3 pathway. Full article

A detailed chemical study of the culture of a coral-derived fungus Penicillium chrysogenum resulted in the isolation and identification of four new aromatic heterocycles chrysoquinazolinones A–B (1–2) and chrysobenzothiazoles A–B (3–4), along with a new sorbicillinoid 4-carboxylsorbicillin (5). Chrysoquinazolinones A–B (1–2) combine a quinazolinone fragment with a bicyclo[2.2.2]octane or a pyrrolidone moiety, respectively, demonstrating the unexpected structures of marine natural products. Chrysobenzothiazoles A–B (3–4) possess a benzothiazole system and are the second isolation of this class of skeleton compounds from marine organisms. The existence of the pair of enantiomers (±3) was deduced by chiral HPLC analysis. Their structures and absolute configurations were elucidated by detailed spectroscopic analysis, comparison with the literature data, single-crystal X-ray crystallographic analysis and TDDFT-ECD calculations. Compound 5 exhibited moderate cytotoxicity against K562 and NCI-H446 cell lines, with IC₅₀ values of 15.00 μM and 16.87 μM, respectively. Full article

Four new sorbicillinoids, named trichodermolide E (1), trichosorbicillin J (2), bisorbicillinolide B (3), and demethylsorbiquinol (5), together with eight known compounds (4, 6–12), were isolated from the cultures of the mangrove-derived fungus Trichoderma reesei BGRg-3. The structures of the new compounds were determined by analyzing their detailed spectroscopic data, while the absolute configurations were further determined through electronic circular dichroism calculations. Snatzke’s method was additionally used to determine the absolute configurations of the diol moiety in 1. In a bioassay, compounds 7 and 10 performed greater inhibitory activities on interleukin-6 and interleukin-1β than the positive control (dexamethasone) at the concentration of 25 μM. Meanwhile, compounds 5 and 6 showed potent effects with stronger inhibition than dexamethasone on IL-1β at the same concentration. Full article

Rice false smut (RFS) caused by Villosiclava virens (anamorph: Ustilaginoidea virens) has become one of the most destructive fungal diseases to decrease the yield and quality of rice grains. An albino strain LN02 was isolated from the white RFS balls collected in the Liaoning Province of China in 2019. The strain LN02 was considered as a natural albino mutant of V. virens by analyzing its phenotypes, internal transcribed spacer (ITS) conserved sequence, and biosynthesis gene clusters (BGCs) for secondary metabolites. The total assembled genome of strain LN02 was 38.81 Mb, which was comprised of seven nuclear chromosomes and one mitochondrial genome with an N50 value of 6,326,845 bp and 9339 protein-encoding genes. In addition, the genome of strain LN02 encoded 19 gene clusters for biosynthesis of secondary metabolites mainly including polyketides, terpenoids and non-ribosomal peptides (NRPs). Four sorbicillinoid metabolites were isolated from the cultures of strain LN02. It was found that the polyketide synthase (PKS)-encoding gene uspks1 for ustilaginoidin biosynthesis in strain LN02 was inactivated due to the deletion of four bases in the promoter sequence of uvpks1. The normal uvpks1 complementary mutant of strain LN02 could restore the ability to synthesize ustilaginoidins. It demonstrated that deficiency of ustilaginoidin biosynthesis is the cause of albinism for RFS albino strain LN02, and V. virens should be a non-melanin-producing fungus. This study further confirmed strain LN02 as a white phenotype mutant of V. virens. The albino strain LN02 will have a great potential in the development and application of secondary metabolites. The physiological and ecological functions of ustilaginoidins in RFS fungus are needed for further investigation. Full article

Three new dimeric sorbicillinoids (1–3) and one new 3,4,6-trisubstituted α-pyrone (5), along with seven analogues (4 and 6–11), were isolated from the mangrove endophytic fungus Trichoderma reesei SCNU-F0042 under the guidance of molecular networking approach. Their chemical structures were established by 1D and 2D NMR HR-ESI-MS and ECD analysis. In a bioassay, compound 2 exhibited moderate SARS-CoV-2 inhibitory activity with an EC₅₀ value of 29.0 μM. Full article

Sorbicillinoids are a class of hexaketide metabolites produced by Ustilaginoidea virens (teleomorph: Villosiclava virens), an important fungal pathogen that causes a devastating rice disease. In this study, we investigated the effects of environmental factors, including carbon and nitrogen sources, ambient pH and light exposure, on mycelial growth, sporulation, as well as the accumulation of sorbicillinoids, and the expression of related genes involved in sorbicillinoid biosynthesis. It was found that the environmental factors had great influences on mycelial growth and sporulation of U. virens. Fructose and glucose, complex nitrogen sources, acidic conditions and light exposure were favorable for sorbicillinoid production. The relative transcript levels of sorbicillinoid biosynthesis genes were up-regulated when U. virens was separately treated with those environmental factors that favored sorbicillinoid production, indicating that sorbicillinoid biosynthesis was mainly regulated at the transcriptional level by different environmental factors. Two pathway-specific transcription factor genes, UvSorR1 and UvSorR2, were found to participate in the regulation of sorbicillinoid biosynthesis. These results will provide useful information to better understand the regulation mechanisms of sorbicillinoid biosynthesis, and be conducive to develop effective means for controlling sorbicillinoid production in U. virens. Full article

Ustilaginoidea virens (teleomorph: Villosiclava virens) is an important fungal pathogen that causes a devastating rice disease. It can produce mycotoxins including sorbicillinoids. The biosynthesis and biological functions of sorbicillinoids have not been reported in U. virens. In this study, we identified a sorbicillinoid biosynthetic gene cluster in which two polyketide synthase genes UvSorA and UvSorB were responsible for sorbicillinoid biosynthesis in U. virens. In ∆UvSorA and ∆UvSorB mutants, the mycelial growth, sporulation and hyphal hydrophobicity were increased dramatically, while the resistances to osmotic pressure, metal cations, and fungicides were reduced. Both phytotoxic activity of rice germinated seeds and cell wall integrity were also reduced. Furthermore, mycelia and cell walls of ∆UvSorA and ∆UvSorB mutants showed alterations of microscopic and submicroscopic structures. In addition, feeding experiment showed that sorbicillinoids could restore mycelial growth, sporulation, and cell wall integrity in ∆UvSorA and ∆UvSorB mutants. The results demonstrated that both UvSorA and UvSorB were responsible for sorbicillinoid biosynthesis in U. virens, and contributed to development (mycelial growth, sporulation, and cell wall integrity), stress responses, and phytotoxicity through sorbicillinoid mediation. It provides an insight into further investigation of biological functions and biosynthesis of sorbicillinoids. Full article

Sorbicillinoids are a class of structurally diverse hexaketide metabolites with good biological activities. To explore new structural sorbicillinoids and their bioactivities, the marine-derived fungus Acremonium chrysogenum C10 was studied. Three new sorbicillinoid derivatives, acresorbicillinols A–C (1–3), along with five known ones, trichotetronine (4), trichodimerol (5), demethyltrichodimerol (6), trichopyrone (7) and oxosorbicillinol (8), were isolated. The structures of new sorbicillinoids were elucidated by analysis of nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS). The absolute configurations of compounds 1–3 were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Compound 3 exhibited a strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, with the IC₅₀ value ranging from 11.53 ± 1.53 to 60.29 ± 6.28 μM in 24 h. Additionally, compounds 2 and 3 showed moderate activities against Staphylococcus aureus and Cryptococcus neoformans, with IC₅₀ values of 86.93 ± 1.72 and 69.06 ± 10.50 μM, respectively. The boundary of sorbicillinoid biosynthetic gene cluster in A. chrysogenum was confirmed by transcriptional analysis, and the biosynthetic pathway of compounds 1–8 was also proposed. In summary, our results indicated that A. chrysogenum is an important reservoir of sorbicillinoid derivatives, and compound 3 has the potential for new natural agents in DPPH radical scavenging. Full article

Trichoderma reesei (Hypocrea jecorina) was developed as a microbial cell factory for the heterologous expression of fungal secondary metabolites. This was achieved by inactivation of sorbicillinoid biosynthesis and construction of vectors for the rapid cloning and expression of heterologous fungal biosynthetic genes. Two types of megasynth(et)ases were used to test the strain and vectors, namely a non-reducing polyketide synthase (nr-PKS, aspks1) from Acremonium strictum and a hybrid highly-reducing PKS non-ribosomal peptide synthetase (hr-PKS-NRPS, tenS + tenC) from Beauveria bassiana. The resulting engineered T. reesei strains were able to produce the expected natural products 3-methylorcinaldehyde and pretenellin A on waste materials including potato, orange, banana and kiwi peels and barley straw. Developing T. reesei as a heterologous host for secondary metabolite production represents a new method for waste valorization by the direct conversion of waste biomass into secondary metabolites. Full article

Four new dimeric sorbicillinoids (1–3 and 5) and a new monomeric sorbicillinoid (4) as well as six known analogs (6–11) were purified from the fungal strain Hypocrea jecorina H8, which was obtained from mangrove sediment, and showed potent inhibitory activity against the tea pathogenic fungus Pestalotiopsis theae (P. theae). The planar structures of 1–5 were assigned by analyses of their UV, IR, HR-ESI-MS, and NMR spectroscopic data. All the compounds were evaluated for growth inhibition of tea pathogenic fungus P. theae. Compounds 5, 6, 8, 9, and 10 exhibited more potent inhibitory activities compared with the positive control hexaconazole with an ED₅₀ of 24.25 ± 1.57 µg/mL. The ED₅₀ values of compounds 5, 6, 8, 9, and 10 were 9.13 ± 1.25, 2.04 ± 1.24, 18.22 ± 1.29, 1.83 ± 1.37, and 4.68 ± 1.44 µg/mL, respectively. Additionally, the effects of these compounds on zebrafish embryo development were also evaluated. Except for compounds 5 and 8, which imparted toxic effects on zebrafish even at 0.625 μM, the other isolated compounds did not exhibit significant toxicity to zebrafish eggs, embryos, or larvae. Taken together, sorbicillinoid derivatives (6, 9, and 10) from H. jecorina H8 displayed low toxicity and high anti-tea pathogenic fungus potential. Full article

An unusual sesquiterpene glycoside trichoacorside A (1) and two novel sorbicillinoid glycosides sorbicillisides A (2) and B (3), together with a known compound sorbicillin (4), were isolated and identified from the culture extract of an endophytic fungus Trichoderma longibrachiatum EN-586, obtained from the marine red alga Laurencia obtusa. Trichoacorside A (1) is the first representative of a glucosamine-coupled acorane-type sesquiterpenoid. Their structures were elucidated based on detailed interpretation of NMR and mass spectroscopic data. The absolute configurations were determined by X-ray crystallographic analysis, chemical derivatization, and DP4+ probability analysis. The antimicrobial activities of compounds 1–4 against several human, aquatic, and plant pathogens were evaluated. Full article

Sorbicillinoids are a family of hexaketide metabolites with a characteristic sorbyl side chain residue. Sixty-nine sorbicillinoids from fungi, newly identified from 2016 to 2021, are summarized in this review, including their structures and bioactivities. They are classified into monomeric, dimeric, trimeric, and hybrid sorbicillinoids according to their basic structural features, with the main groups comprising both monomeric and dimeric sorbicillinoids. Some of the identified sorbicillinoids have special structures such as ustilobisorbicillinol A, and sorbicillasins A and B. The majority of sorbicillinoids have been reported from fungi genera such as Acremonium, Penicillium, Trichoderma, and Ustilaginoidea, with some sorbicillinoids exhibiting cytotoxic, antimicrobial, anti-inflammatory, phytotoxic, and α-glucosidase inhibitory activities. In recent years, marine-derived, extremophilic, plant endophytic, and phytopathogenic fungi have emerged as important resources for diverse sorbicillinoids with unique skeletons. The recently revealed biological activities of sorbicillinoids discovered before 2016 are also described in this review. Full article

In the search for antifungal agents from marine resources, we recently found that the culture filtrate of Trichoderma longibrachiatum SFC100166 effectively suppressed the development of tomato gray mold, rice blast, and tomato late blight. The culture filtrate was then successively extracted with ethyl acetate and n-butanol to identify the fungicidal metabolites. Consequently, a new compound, spirosorbicillinol D (1), and a new natural compound, 2′,3′-dihydro-epoxysorbicillinol (2), together with 11 known compounds (3–13), were obtained from the solvent extracts. The chemical structures were determined by spectroscopic analyses and comparison with literature values. The results of the in vitro antifungal assay showed that of the tested fungal pathogens, Phytophthora infestans was the fungus most sensitive to the isolated compounds, with MIC values ranging from 6.3 to 400 µg/mL, except for trichotetronine (9) and trichodimerol (10). When tomato plants were treated with the representative compounds (4, 6, 7, and 11), bisvertinolone (6) strongly reduced the development of tomato late blight disease compared to the untreated control. Taken together, our results revealed that the culture filtrate of T. longibrachiatum SFC100166 and its metabolites could be useful sources for the development of new natural agents to control late blight caused by P. infestans. Full article

Overexpression of the global regulator LaeA in a marine-derived fungal strain of Penicillium dipodomyis YJ-11 induced obvious morphological changes and metabolic variations. Further chemical investigation of the mutant strain afforded a series of sorbicillinoids including two new ones named 10,11-dihydrobislongiquinolide (1) and 10,11,16,17-tetrahydrobislongiquinolide (2), as well as four known analogues, bislongiquinolide (3), 16,17-dihydrobislongiquinolide (4), sohirnone A (5), and 2′,3′-dihydrosorbicillin (6). The results support that the global regulator LaeA is a useful tool in activating silent gene clusters in Penicillium strains to obtain previously undiscovered compounds. Full article