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Soil-borne pathogens and weeds could synergistically affect vegetable growth and result in serious losses. The investigation of antagonistic metabolites from a marine-derived entomopathogenic fungus, Beauveria felina, obtained polyhydroxy steroid (1), tricyclic diterpenoid (2), isaridin (3), and destruxin cyclodepsipeptides (4-6). The structures and absolute configurations of new 1-3 were elucidated by extensive spectroscopic and X-ray crystallographic analyses, as well as electronic circular dichroism (ECD) calculations. Compounds 1 and 2 showed antifungal activities against carbendazim-resistant strains of Botrytis cinerea, with the minimum inhibitory concentration (MIC) values ranging from 16 to 32 μg/mL, which were significantly better than those of carbendazim (MIC = 256 μg/mL). Compound 5 exhibited significant antagonistic activity against the radicle growth of Amaranthus retroflexus seedlings, which was almost identical to that of the positive control (2,4-dichlorophenoxyacetic acid). The structure-activity differences of 4-6 suggested that the Cl atom in HMPA1 and β-Me in Pro2 should be the key factors to their herbicidal activities. Besides, compounds 3-6 showed moderate nematicidal activities against Meloidogyne incognita. These antagonistic effects of 1-6 were first reported and further revealed the synergistically antagonistic potential of B. felina to be developed into the biopesticide.

The AcOEt extract of Artemisia argyi-derived fungus Trichoderma koningiopsis QA-3 showed potent inhibitory activity against pathogenic bacteria. Fractionation of the extract resulted in the isolation of three new polyketides (1-3) and two new terpenoids (4 and 5), together with three known metabolites (6-8). Their chemical structures were analyzed by NMR spectra, ECD, HR-ESI-MS or HR-EI-MS, optical rotation, and X-ray crystallographic data, as well as by comparison with literature reports. In the antibacterial assays, 3-hydroxyharziandione (4) showed potent activity against human pathogen Escherichia coli with an MIC value of 0.5 μg/mL, while 6-(3-hydroxypent-1-en-1-yl)-2H-pyran-2-one exhibited strong activity against marine-derived aquatic pathogen Micrococcus luteus with an MIC value of 1.0 μg/mL.

Soil-borne pathogens, including phytopathogenic fungi and root-knot nematodes, could synergistically invade vegetable roots and result in serious economic losses. The genus of Trichoderma has been proven to be a promising reservoir of biocontrol agents in agriculture. In this study, the search for antagonistic metabolites from a marine-derived fungus, Trichoderma longibrachiatum, obtained two structural series of sesquiterpenes 1−6 and cyclodepsipeptides 7−9. Notably, the novel 1 was a rare norsesquiterpene characterized by an unprecedented tricyclic-6/5/5-[4.3.1.01,6]-decane skeleton. Their structures were elucidated by extensive spectroscopic analyses, while the absolute configuration of novel 1 was determined by the comparison of experimental and calculated ECD spectra. The novel 1 and known 2 and 3 showed significant antifungal activities against Colletotrichum lagrnarium with MIC values of 8, 16, and 16 μg/mL respectively, even better than those of the commonly used synthetic fungicide carbendazim with 32 μg/mL. They also exhibited antifungal potential against carbendazim-resistant Botrytis cinerea. Cyclodepsipeptides 7−9 showed moderate nematicidal activities against the southern root-knot nematode (Meloidogyne incognita). This study constitutes the first report on the antagonistic effects of metabolites from T. Longibrachiatum against soil-borne pathogens, also highlighting the integrated antagonistic potential of marine-derived T. Longibrachiatum as a biocontrol agent.

In the search for antifungal lead compounds from natural resources, Notopterygium incisum, a medicine plant only distributed in China, showed antifungal potential against apple fruit pathogens. Based on the bioassay-guided isolation, chromatography fraction 6 of the ethyl acetate partition exhibited significant in vitro and in vivo antifungal activities against apple fruit pathogens. Furthermore, nine antifungal secondary metabolites, including five linear furocoumarins (1–5), two phenylethyl esters (6–7), one falcarindiol (8), and one sesquiterpenoid (9), were isolated and elucidated from fraction 6. Compound 5 is a new metabolite, and 9 isolated from the genus Notopterygium for the first time. The purified compounds (1–9) were firstly reported to exhibit antifungal activities against apple fruit pathogens of Colletotrichum gloeosporioides and Botryosphaeria dothidea with the MIC values ranging from 8 to 250 mg L−1, especially 8 of 16 and 8 mg L−1, respectively. Moreover, 8 could inhibit the spore germination and new sporulation of B. dothidea, as well as enhance the membrane permeabilization of B. dothidea spores. This was the first investigation for the antifungal components against apple fruit pathogens from Notopterygium incisum, which has great potential to be developed into bio-fungicides.

Botrytis cinerea is one of the most destructive fungal pathogens which can cause gray mold diseases of numerous plant species, while the frequent applications of fungicides also result in the fungicide-resistances of B. cinerea. In this study, a new Streptomyces strain FX13 was obtained to show biocontrol potentials against fungicide-resistant B. cinerea B3–4. Its in vitro and in vivo antifungal mechanisms were further investigated. The results showed that the culture extract of strain FX13 could significantly inhibit the mycelia growth of B. cinerea B3–4 with the EC50 value of 5.40 mg L−1, which was greatly lower than those of pyrisoxazole, boscalid and azoxystrobin. Further bioassay-guided isolation of the extract had yielded the antifungal component SA1, which was elucidated as a 26-membered polyene macrolide of oligomycin A. SA1 could inhibit the mycelia growth, spore germination, germ tube elongation and sporogenesis of B. cinerea B3–4 in vitro, and also showed significant curative and protective effects against gray mold on grapes in vivo. Moreover, SA1 could result in the loss of membrane integrity and the leakage of cytoplasmic contents, which might be related to the accumulation of reactive oxygen species (ROS) and membrane lipid peroxidation. Besides, intracellular adenosine triphosphatase (ATPase) activity and adenosine triphosphate (ATP) content of B. cinerea B3–4 decreased after SA1-treatment. Overall, the oligomycin A-producing strain FX13 could inhibit fungicide-resistant B. cinerea B3–4 in vitro and in vivo, also highlighting its biocontrol potential against gray mold.

Candida albicans and Cryptococcus neoformans, human-pathogenic fungi found worldwide, are receiving increasing attention due to high morbidity and mortality in immunocompromised patients. In the present work, 110 fungus pairs were constructed by coculturing 16 wood-decaying basidiomycetes, among which coculture of Trametes robiniophila Murr and Pleurotus ostreatus was found to strongly inhibit pathogenic fungi through bioactivity-guided assays. A combination of metabolomics and molecular network analysis revealed that 44 features were either newly synthesized or produced at high levels in this coculture system and that 6 of the features that belonged to a family of novel and unusual linear sesterterpenes contributed to high activity with MICs of 1 to 32 μg/ml against pathogenic fungi. Furthermore, dynamic 13C-labeling analysis revealed an association between induced features and the corresponding fungi. Unusual sesterterpenes were 13C labeled only in P. ostreatus in a time course after stimulation by the coculture, suggesting that these sesterterpenes were synthesized by P. ostreatus instead of T. robiniophila Murr. Sesterterpene compounds 1 to 3 were renamed postrediene A to C. Real-time reverse transcription-quantitative PCR (RT-qPCR) analysis revealed that transcriptional levels of three genes encoding terpene synthase, farnesyl-diphosphate farnesyltransferase, and oxidase were found to be 8.2-fold, 88.7-fold, and 21.6-fold higher, respectively, in the coculture than in the monoculture, indicating that biosynthetic gene cluster 10 was most likely responsible for the synthesis of these sesterterpenes. A putative biosynthetic pathway of postrediene A to postrediene C was then proposed based on structures of sesterterpenes and molecular network analysis. IMPORTANCE A number of gene clusters involved in biosynthesis of secondary metabolites are presumably silent or expressed at low levels under conditions of standard laboratory cultivation, resulting in a large gap between the pool of discovered metabolites and genome capability. This work mimicked naturally occurring competition by construction of an artificial coculture of basidiomycete fungi for the identification of secondary metabolites with novel scaffolds and excellent bioactivity. Unusual linear sesterterpenes of postrediene A to C synthesized by P. ostreatus not only were promising lead drugs against human-pathogenic fungi but also highlighted a distinct pathway for sesterterpene biosynthesis in basidiomycetes. The current work provides an important basis for uncovering novel gene functions involved in sesterterpene synthesis and for gaining insights into the mechanism of silent gene activation in fungal defense.

A new triterpenoid saponin, named oleiferasaponin A2, was isolated and identified from Camellia oleifera defatted seeds. Oleiferasaponin A2 exhibited anti-hyperlipidemic activity on HepG2 cell lines. Further study of the hypolipidemic mechanism showed that oleiferasaponin A2 inhibited fatty acid synthesis by significantly down-regulating the expression of SREBP-1c, FAS and FAS protein, while dramatically promoting fatty acid &beta, oxidation by up-regulating the expression of ACOX-1, CPT-1 and ACOX-1 protein. Our results demonstrate that the oleiferasaponin A2 possesses potential medicinal value for hyperlipidemia treatment.

One new and three known triterpenoid saponins were isolated and identified from Camellia oleifera seeds through IR, NMR, HR-ESI-MS and GC-MS spectroscopic methods, namely oleiferasaponin A3, oleiferasaponin A1, camelliasaponin B1, and camelliasaponin B2. The structure of oleiferasaponin A3 was elucidated as 16α-hydroxy-21β-O-angeloyl-22α-O-cinnamoyl-23α-aldehyde-28-dihydroxymethylene-olean-12-ene-3β-O-[β-d-galactopyranosyl-(1→2)]-[β-d-xylopyranosyl-(1→2)-β-d-galactopyranosyl-(1→3)]-β-d-gluco-pyranosiduronic acid. Camelliasaponin B1 and camelliasaponin B2 exhibited potent cytotoxic activity on three human tumour cell lines (human lung tumour cells (A549), human liver tumour cells (HepG2), cervical tumour cells (Hela)). The hypoglycemic activity of oleiferasaponin A1 was testified by protecting pancreatic β-cell lines from high-glucose damage.

Four new indolediketopiperazine derivatives (1–4), along with nine known congeners (5–13), were isolated and identified from the culture extract of Eurotium cristatum EN-220, an endophytic fungus obtained from the marine alga Sargassum thunbergii. The structures of thesecompounds were elucidated on the basis of extensive spectroscopic analysis and the absolute configurations of compounds 1–4 were established by NOESY experiments and by chiral HPLC analyses of their acid hydrolysates. The absolute configuration of C-8 (a quaternary carbon substituted with a hydroxyl group) in 5 of preechinulin class was firstly determined by electronic circular dichroism (ECD) calculations. All these compounds were evaluatedfor brine shrimp (Artemia salina) lethality and nematicidal activity as well as antioxidativeand antimicrobial potency.

Cultivation of the fungal strain Eurotium cristatum EN-220, an endophyte obtained from the marine alga Sargassum thunbergii, resulted in the isolation of one new anthraquinone glycoside, 3-O-(alpha-D-ribofuranosyl)questinol (1) and one new orsellinic acid ester, cristatumside A (2), together with three known aromatic glycosides, 3-O-(alpha-D-ribofuranosyl)questin (3), isotorachrysone 6-O-alpha-D-ribofuranoside (4), and asperflavin ribofuranoside (5), as well as three anthraquinone derivatives, asperflavin (6), eurorubrin (7), and (+)-variecolorquinone A (8). The structures of these compounds were determined by extensive analysis of their spectroscopic data, as well as by their comparison with those in the literature. Each of the isolated compounds was evaluated for its antimicrobial activity and brine shrimp lethality.

Bioassay-guided fractionation of a culture extract of Beauveria felina EN-135, an entomopathogenic fungus isolated from a marine bryozoan, led to the isolation of a new cyclodepsipeptide, iso-isariin D (1); two new O-containing heterocyclic compounds that we have named felinones A and B (2 and 3); and four known cyclodepsipeptides (4–7). The structures were elucidated via spectroscopic analysis, and the absolute configurations of 1 and 2 were determined using single-crystal X-ray diffraction and CD, respectively. All isolated compounds were evaluated for antimicrobial activity and brine-shrimp (Artemia salina) lethality.

On the basis of the &lsquo, one strain, many compounds&rsquo, (OSMAC) strategy, chemical investigation of the marine-derived fungus Trichothecium roseum resulted in the isolation of trichomide cyclodepsipeptides (compounds 1&ndash, 4) from PDB medium, and destruxin cyclodepsipeptides (compounds 5&ndash, 7) and cyclonerodiol sesquiterpenes (compounds 8&ndash, 10) from rice medium. The structures and absolute configurations of novel (compounds 1, 8, and 9) and known compounds were elucidated by extensive spectroscopic analyses, X-ray crystallographic analysis, and ECD calculations. All isolated compounds were evaluated for cytotoxic, nematicidal, and antifungal activities, as well as brine shrimp lethality. The novel compound 1 exhibited significant cytotoxic activities against the human cancer cell lines MCF-7, SW480, and HL-60, with IC50 values of 0.079, 0.107, and 0.149 &mu, M, respectively. In addition, it also showed significant brine shrimp lethality, with an LD50 value of 0.48 &mu, M, and moderate nematicidal activity against Heterodera avenae, with an LC50 value of 94.9 &mu, g/mL. This study constitutes the first report on the cytotoxic and nematicidal potential of trichomide cyclodepsipeptides.

Penicillium chrysogenum QEN-24S, an endophytic fungus isolated from an unidentified marine red algal species of the genus Laurencia, displayed inhibitory activity against the growth of pathogen Alternaria brassicae in dual culture test. Chemical investigation of this fungal strain resulted in the isolation of four new (1-3 and 5) and one known (4) secondary metabolites. Their structures were identified as two polyketide derivatives penicitides A and B (1 and 2), two glycerol derivatives 2-(2,4-dihydroxy-6-methylbenzoyl)-glycerol (3) and 1-(2,4-dihydroxy-6-methylbenzoyl)- glycerol (4), and one monoterpene derivative penicimonoterpene (5). Penicitides A and B (1 and 2) feature a unique 10-hydroxy- or 7,10-dihydroxy-5,7-dimethylundecyl moiety substituting at C-5 of the α-tetrahydropyrone ring, which is not reported previously among natural products. Compound 5 displayed potent activity against the pathogen A. brassicae, while compound 1 exhibited moderate cytotoxic activity against the human hepatocellular liver carcinoma cell line.

Three new indolediketopiperazine alkaloids of the isoechinulin type, rubrumazines A-C (1-3), each possessing an oxygenated prenyl group either at C-7 (1 and 2) or at C-5 (3), along with 13 related analogues (4-16), were isolated and identified from a culture extract of Eurotium rubrum MA-150, a fungus obtained from mangrove-derived rhizospheric soil collected from the Andaman Sea coastline, Thailand. Their structures were established by detailed interpretation of NMR spectroscopic and mass spectrometry data analysis. The structure and absolute configuration of compound 1 were confirmed by X-ray crystallographic analysis, thus providing the first characterized crystal structure of an isoechinulin-type alkaloid. All isolated compounds were evaluated for brine shrimp lethality and antibacterial activity.

The alkaloid varioexpine A (I) is isolated from the marine fungus Paecilomyces variotii and its structure is characterized by NMR spectroscopy and X-ray analysis.

A new 3H-oxepine-containing alkaloid, varioxepine A (1), characterized by a structurally unprecedented condensed 3,6,8-trioxabicyclo[3.2.1]octane motif, was isolated from the marine algal-derived endophytic fungus Paecilomyces variotii. Due to the low proton/carbon ratio, the unambiguous assignment of the planar structure and relative configuration was precluded by NMR experiments and solved by single crystal X-ray analysis. The absolute configuration was established by DFT conformational analysis and TDDFT-ECD calculations. Compound 1 inhibited plant pathogenic fungus Fusarium graminearum.

Three new cyclohexadepsipeptides of the isaridin class including isaridin G (1), desmethylisaridin G (2), and desmethylisaridin C1 (3), along with three related known metabolites (4-6), were isolated and identified from the marine bryozoan-derived fungus Beauveria felina EN-135. The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis, and the structures and absolute configurations of compounds 1-3 were confirmed by single-crystal X-ray diffraction analysis. The crystal structures showed the presence of beta-turns for the Tyr(3)/N-Me-Val(4) and Phe(3)/N-Me-Val(4) amide bonds in compounds 2 and 3, respectively, in the cis conformations, which were opposite other reported isaridins. The conformations of the HMPA(1)-Pro(2) amide bond in compound 2 are different in the solution and in the crystal structures, which showed trans and cis geometries, respectively, while compounds 1 and 3 do not exhibit this phenomenon. Each of the isolated compounds was evaluated for antimicrobial activity and brine shrimp lethality. Compound 3 exhibited antibacterial activity against E. coli with an MIC value of 8 mu g/mL.

Chemical investigation of the mycelial extract of a mixed culture of two marine alga-derived fungal strains of the genus Aspergillus has yielded one new cyclotripeptide, psychrophilin E (1), the recently reported oxepin-containing alkaloids, protuboxepin A (2) and oxepinamide E (3), together with three other polyketide derivatives (4–6). The chemical structure and relative and absolute configurations of psychrophilin E (1) were unambiguously established based on HRMS, 1D, 2D NMR and chiral-phase HPLC analysis of its hydrolysate. All the isolated compounds were assessed for their anti-proliferative activity against four different human cancer cell lines and some of them revealed selective activities.

Four new indole alkaloids, namely, cristatumins A–D (1–4), along with six known congeners (5–10) were identified from the culture extract of Eurotium cristatum EN-220, an endophytic fungus isolated from the marine alga Sargassum thunbergii. The structures of these compounds were established on the basis of extensive spectroscopic analysis. Each of these compounds was evaluated for antimicrobial and insecticidal activity. Compounds 1 and 9 showed antibacterial activity against Escherichia coli and Staphyloccocus aureus, respectively, while compounds 2, 6, and 7 exhibited moderate lethal activity against brine shrimp. Preliminary structure–activity relationships were also discussed.