Artemisia argyi Levl. et Van. var. argyi cv. Qiai is a commercially important medicinal plant specifically cultivated in Qichun County, Hubei Province of Central China. Investigation of the antibacterial functional constituents of the endophytic Fusarium asiaticum QA-6, which is derived from Qiai, resulted in the characterization of nine previously undescribed polyketides fusarielins Q-Y (compounds 1-9) and two known congeners fusarielins M (compound 10) and F (compound 11). Structurally, compounds 1-9 possess a highly functionalized decalin moiety, whereas compounds 1-3 feature shorter polyene side chains compared to other fusarielins. The shortened chain in 2 and 3 likely results from a missed S-adenosyl-l-methionine (SAM)-dependent methylation, with 3 being an oxidation product of 2. Conversely, the truncation in 1 may stem from a missed acetyl-CoA addition. The isolated compounds were assayed for antibacterial activity against aquatic bacterial pathogens, among which, compounds 1, 5, 10, and 11 exhibited activity against specific Gram-negative strains, with compound 1 inhibited Aeromonas hydrophilia (MIC = 2.92 μM) and Vibrio alginolyticus (MIC = 5.84 μM), compound 5 targeted the aquatic pathogen Edwardsiella ictarda (MIC = 2.39 μM), compound 10 acted against E. ictarda, Vibrio harveyi, and V. parahaemolyticus (each with an MIC value of 2.60 μM), and compound 11 inhibited V. alginolyticus (MIC = 4.80 μM). All these antibacterial activities were equivalent to or superior to those of the positive control, chloramphenicol (MICs = 1.55 to 6.19 μM). In the preliminary screening against HeLa cells, none of the isolated compounds exhibited significant cytotoxic activity at the concentration 20 μM.

Two orsellinic acid (OA)-derived metabolites, chermsinols A and B (1 and 2), were isolated from the marine red alga-derived endophytic Penicillium chermesinum EN-480 based on its genomic analysis. Compound 1 is a steroid featuring an unprecedented 6/6/6/5/6/6 ring system, likely formed from a Diels-Alder reaction, while compound 2 is a meroterpenoid containing a unique ring-opened ketone chain derived from 3,5-dimethylorsellinic acid (DMOA) and possessing a continuous spiro system. Results from bioassays revealed that compound 1 exhibits inhibitory activity against influenza neuraminidase as well as antibacterial properties. The plausible biosynthetic pathways for 1 and 2 were proposed on the basis of the genomic data analysis of the producing fungus.

[This corrects the article DOI: 10.3892/ol.2018.9486.].

Eight depsidone derivatives (1-8), including three new compounds designated as westersidones A-C (1-3), were isolated from Westerdykella dispersa CS-734, an endozoic fungus derived from the deep-sea cold seep mussel Gigantidas platifrons. Their structures were elucidated through extensive spectroscopic analysis, including HRESIMS, NMR, and single-crystal X-ray diffraction. Remarkably, compound 1 represents a rare and unprecedented hybrid natural product formed by the fusion of a depsidone and a naphtho-γ-pyrone skeleton. The antibacterial activities against human and aquatic pathogens of the isolated compounds were assayed. Notably, compound 8 exhibited the most potent activity against several tested strains, with MICs 4-16 µg/mL, underscoring the critical role of the C-4 aldehyde group in enhancing antimicrobial potency.

Three novel polyketides, talaroindiones A-C (1-3), along with two known diphenyl ether derivatives (4 and 5) were isolated from the rice culture medium extract of the marine-derived fungus Talaromyces indigoticus CS-469. The structures of 1-3 were determined by comprehensive spectroscopic analysis and confirmed by single-crystal x-ray diffraction. Their absolute configurations were assigned using TDDFT-ECD calculations, while those of 4 and 5 were established by comparison of their experimental optical rotations with literature values. All compounds were evaluated for their antibacterial activity. Compound 4 exhibited broad-spectrum inhibitory activities against six bacterial strains, showing particularly potent activity against Vibrio harveyi and Vibrio parahaemolyticus with MIC values of 2 µg/mL.

Artemisia argyi H. Lév. & Vaniot, an Asteraceae family herb, is extensively used in traditional Chinese pharmacopoeia and is a major local crop in Qichun County, possessing notable medicinal, economic, and cultural value. Its associated endophytes represent promising microbial candidates for natural product discovery. To investigate this potential, 40 fungal strains were isolated from A. argyi, and 12 with distinctive colony morphology were selected for scaled-down fermentation. Their EtOAc extracts were subsequently evaluated using HPLC, TLC, and antibacterial assays. Strain Epicoccum sorghinum QA-20, which displayed notable antibacterial effects, was chosen for further chemical investigation. Chromatographic separation from fermented broth extract yielded one previously undescribed polyketide, 7-methoxy-4,9-dimethyldibenzo[b,e][1,4]dioxin-2-ol (1), together with 12 known compounds (2–13). Structural elucidation was performed using NMR and/or mass spectrometry. Further structural confirmation of compound 1 was achieved through X-ray crystallographic analysis. All isolated compounds were investigated for antibacterial and antioxidant activities. Compounds 5–7 were effective in suppressing growth of pathogenic microbes, while compounds 1, 6, and 7 exhibited significant free radical scavenging activity. Compound 6 exhibited the broadest antibacterial spectrum, inhibiting all seven tested strains (MICs = 12.5–100 μg/mL); while compound 7 exhibited DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2’-azino-bis) scavenging capacity (IC50=15.81 ± 0.52and 32.95 ± 0.72 μg/mL, respectively), comparable to that of vitamin C (IC50 = 11.62 ± 0.85 and 28.09 ± 1.40 μg/mL, respectively). This study demonstrates that endophytes derived from A. argyi are a valuable source of novel antibacterial and antioxidant natural products.

Three new highly oxygenated acorane sesquiterpenes, namely, 9,10-epoxidicacoren-2,7,8-triol (1), 8S-acoren-2,7,8-triol (2), and 8R-acoren-2,7,8-triol (3), along with four known analogs (4-7), were isolated from the deep-sea derived fungus Trichoderma harzianum CS-152. Except for compound 7, the other compounds lack conjugation and do not exhibit fluorescence under UV light at 254 nm, which posed a challenge in their detection and required careful monitoring during separation. The isolation and purification of these compounds was achieved using traditional silica gel column chromatography. Their chemical structures and relative configurations were elucidated by comprehensive analysis of 1D/2D NMR, HRESIMS, and their absolute configurations were determined by modified Mosher's method. Compounds 1 and 4 displayed inhibitory activities against the aquatic pathogen Aeromonas hydrophila, each with a MIC value 4 μg/mL, while compound 7 showed antibacterial activity against Pseudomonas aeruginosa with a MIC value 4 μg/mL.

Talarodride I (1), the first representative of penta-nor-nonadride derivative having a caged bicyclo[4.3.1]deca-2,6-diene core skeleton with an aldehyde group at C-15, together with a new congener talarodride J (2) and five known secondary metabolites (3-7), were isolated and identified from the Magellan seamount-sourced sea-anemone endozoic fungus Talaromyces scorteus AS-242. Their structures were assigned by nuclear magnetic resonance and mass spectroscopic data analysis and time-dependent density functional theory electronic circular dichroism calculations. In the antibacterial assays compounds 1-5 displayed activities against a broad spectrum of human- and aquatic pathogens, with compounds 1 and 2 showing potent inhibitory effects against Escherichia coli and Aeromonas hydrophilia (minimum inhibitory concentration values 1-4 µg/mL).

Ten cytochalasin derivatives, including six new methylthioether-containing chaetoglobosins (thiochaetoglobosins A-F, 1-6), a new related congener (18-nor-prochaetoglobosin II, 7), and three known unsulfured counterparts (8-10), were isolated and identified from Chaetomium globosum AS-506, an endozoic fungus isolated from a deep-sea sponge, which was collected from Magellan Seamounts in the Western Pacific Ocean. Their structures were determined by extensive interpretation of the spectroscopic and X-ray crystallographic data, as well as by ECD calculations. Structurally, thiochaetoglobosins A-F (1-6) represent the first examples of chaetoglobosin derivatives containing a methylthioether group in the molecules, while 18-nor-prochaetoglobosin II (7) is the first 18-nor-chaetoglobosin derivative. Precursor incubation experiments with [13C-CH3]-l-methionine confirmed that the thio-linked methyl was derived from methionine, and a new isotope-labeled thiochaetoglobosin (11) was also isolated and identified. Compound 7 exhibited activity against the aquatic pathogenic bacterium Vibrio alginolyticus (MIC = 0.5 μg/mL), comparable to that of the positive control chloramphenicol. The cell morphology of V. alginolyticus was studied by using growth curves and scanning electron microscopy (SEM) data. The results showed that compound 7 could affect the integrity of the membrane to induce bacteriolysis and death of V. alginolyticus. Additionally, compounds 1, 4, 5, 7, and 9 showed cytotoxic activities against several tumor cell lines with IC50 values ranging from 0.72 to 17.66 μM.

Seven previously undescribed polyketide derivatives, fusariumtides A-G (1-7), together with three known analogues (8-10), were isolated from the culture extract of Fusarium asiaticum QA-6, an endophytic fungus obtained from the fresh stem tissue of the medicinal plant Artemisia argyi H. Lev. & Vaniot. Their structures were elucidated by detailed interpretation of 1D/2D NMR spectroscopic and mass spectrometric data, and the absolute configuration of compound 1 was established on the basis of X-ray crystallographic analysis and ECD and specific rotation (SR) calculations. The isolated compounds, which possessed a functionalized decalin moiety, were evaluated for antimicrobial activities. Compounds 1 and 10 exhibited broad-spectrum inhibitory activities against nine tested pathogenic bacteria with MIC values ranging from 1 to 64 μg/mL, while compound 8 showed potent inhibitory activities against aquatic pathogens Aeromonas hydrophilia, Pseudomonas aeruginosa, Vibrio harveyi, and V. vulnificus, which were comparable to/or stronger than those of the positive control chloramphenicol.

Three new meroterpenoids, tricycloalternarenes P and Z (1 and 2), and didehydrotricycloalternarene Z (3), together with nine known congeners (4-12), were obtained from the culture of Alternaria alstroemeriae, a fungus isolated from the sunken logs collected from the cold seep environment in the South China Sea. Their structures were determined by detailed interpretation of nuclear magnetic resonance (NMR) spectroscopy spectroscopic and mass spectrometric data. The relative configurations of compounds 1-3 were assigned by nuclear Overhauser effect spectroscopy correlations combined with gauge-independent atomic orbital NMR shift calculations and DP4+ probability analysis, while their absolute configurations were assigned by time-dependent density functional theory electronic circular dichroism calculations. The biological analysis results revealed that compounds 1-4, 7, and 9-11 showed antibacterial activities against Klebsiella pneumonia and methicillin-resistant Staphylococcus aureus with minimum inhibitory concentrations of 22.2-100 µM.

Cold seep ecosystems harbor unique microbial communities with potential for producing secondary metabolites. However, the metabolic potential of cold seep microorganisms in the South China Sea remains under-recognized. This study employed both culture-dependent and culture-independent approaches, including 16S rRNA amplicon sequencing and metagenomics, to investigate microbial communities and their potential for secondary metabolite production in the South China Sea cold seep. The results indicate microbial composition varied little between two non-reductive sediments but differed significantly from the reductive sediment, primarily due to Planctomycetes and Actinobacteria. Predicting the Secondary Metabolism Potential using Amplicon (PSMPA) predictions revealed 115 strains encoding more than 10 biosynthetic gene clusters (BGCs), with lower BGC abundance in reductive sediment. Culture-dependent studies showed Firmicutes as the dominant cultivable phylum, with strains from shallow samples encoding fewer BGCs. Metagenomic data confirmed distinct microbial compositions and BGC distributions across sediment types, with cold seep type having a stronger influence than geographic location. Certain BGCs showed strong correlations with sediment depth, reflecting microbial adaptation to nutrient-limited environments. This study provides a comprehensive analysis of the metabolic capabilities of South China Sea cold seep microorganisms and reveals key factors influencing their secondary metabolic potential, offering valuable insights for the efficient exploration of cold seep biological resources.

A new curvularin derivative, curvulone C (1) and a pair of new norlignanolide diastereomers, aspergilfuranone E (2) and 8-epi-aspergilfuranone E (3), together with six known secondary metabolites (4-9) were isolated and identified from the coculture of the marine mangrove endophytic fungus Penicillium brocae MA-231 and phytopathogen Curvularia spicifera QA-26. Their structures were elucidated on the basis of spectroscopic analysis, and the absolute configurations were assigned on the basis of time-dependent density functional theory-electronic circular dichroism calculations. Compounds 1 and 4 showed inhibitory activities against several human and aquatic pathogens.

Indoloditerpenoids (IDTs) are a group of fungal metabolites that have attracted considerable attention from natural product chemists due to their diverse structures and potent bioactivities. A total of 317 IDTs is included in this review, and some of them exhibit antitumor, antiinsectan, antifungal, and antibacterial activities. Among them, 60% IDTs were isolated from marine-derived fungi, indicating the significant role of the marine ecological environment. The chemical structures of IDTs have been determined mainly by NMR, MS, and X-ray crystallographic analysis, while the absolute configurations have been largely assigned by Mosher’s method and chiral spectroscopic protocols such as computed ECD, VCD, and optical rotations. This review covers the literature up to the middle of 2025, illustrating the chemical diversity of IDTs from the fungal kingdom. Biosynthesis and organic synthesis of IDTs are also summarized.

Chemical investigation of the cold-seep-sourced fungus Talaromyces trachyspermus CS-106 resulted in the isolation of six previously undescribed phenolic glucopyranosides, talarosides A-F (1-6), two previously undescribed phenolic cysteine derivatives, talacysteines A and B (7 and 8), and five known congeners 9-13. The results from in vitro bioassay indicated that compounds 3, 6, and 9 displayed potent activities against several tested phytopathogenic fungal strains. Specially, the chloroquinone derivative, 2-chloro-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione (compound 9), exhibited a broad spectrum of fungicidal activity against Alternaria brassicae, Colletotrichum gloeosporioides, Fusarium graminearum, and F. oxysporum, with MIC values ranging from 0.5 to 4 μg/mL. In vivo testing on tomato fruits showed that 9 displayed considerable curative efficacy against F. oxysporum. Both scanning electron microscopy and cryo-SEM analysis indicated that 9 possessed a strong ability to destroy the surface morphology of mycelia and seriously interfere with the growth of the fungal pathogen. Compound 9 also exhibited pronounced succinate dehydrogenase (SDH) inhibitory activity from the in vitro SDH inhibitory assay. Molecular docking simulations were performed to explore the intermolecular interaction of 9 with SDH enzyme from F. oxysporum. These findings presented a promising lead compound such as compound 9 for the discovery of SDH inhibitor as antifungal agents.

Six previously undescribed spiromeroterpenoids, chermesins I-N (1-6), were isolated and identified from the marine-sourced fungus Penicillium chermesinum AS-400. Their structures were determined by nuclear magnetic resonance and mass spectroscopic data, and the relative and absolute configurations were confirmed based on nuclear Overhauser effect spectroscopic experiments, electronic circular dichroism (ECD) calculations and X-ray crystallographic analysis, and by comparisons of ECD Cotton effects with those of known congeners as well. Structurally, compound 1 represents the first example of spiromeroterpenoid demethylated at C-4. The isolated compounds exhibited inhibitory activities against several aquatic and human pathogenic bacteria with MIC values ranging from 4 to 64 μg/mL.

Nine unreported (chermesirenins A-I, 1-9) and one known (eupenicisirenin C, 10) sirenin sesquiterpenoids as well as two unreported bisabolane-type sesquiterpenoids (chermebisabolins A and B, 11 and 12) were isolated from two isolates of marine-sourced fungal strains Penicillium chermesinum EN-480 and AS-400, which were obtained as endophytic and endozoic fungi from the marine red alga Pterocladiella tenuis and the marine chiton Liolophura japonica, respectively. The sirenin sesquiterpenoids (1-9) featured with unique 6/3 dicyclic ring system while compounds 8 and 9 are nor-sirenin analogs by degrading the C-12 methyl group. Their structures including stereochemical configurations were confirmed through NMR interpretation, ECD analysis, Mosher's method, X-ray crystallographic diffraction, and quantum chemical calculations. The anti-osteoporotic activity evaluation in the zebrafish osteoporosis model revealed that chermesirenin A (1) could significantly alleviate the reduction of bone fluorescence area and fluorescence density in prednisolone-treated zebrafish. Furthermore, compound 1 could down-regulate the expression of the genes associated with prednisolone-induced osteoclastogenesis, ctsk and tnfrsf11b, to improve bone formation status. Exploration on the mechanism through the transcriptomic analysis showed that compound 1 might act on the NOD-like receptor (NLR) signaling pathway involved in inflammatory responses and bone metabolism regulation, which has not been reported among previous investigations on sesquiterpenoids. These results demonstrated that compound 1 deserved further development as a potential candidate towards the therapy of osteoporotic disease.

Although anisotropic NMR spectroscopy has emerged as a powerful method for determining the relative configuration of complex natural products, major challenges persist with structurally flexible molecules. In this study, we conducted a systematic comparative analysis of stereochemical elucidation, combining anisotropic NMR spectroscopy and density functional theory (DFT) calculations on spiroepicoccin B (1) and epicoccin V (2), which were characterized as thiodiketopiperazine marine natural products isolated from the deep-sea-derived fungus Epicoccum nigrum SD-388. For the flexible compound 2, we compared various conformational sampling approaches, including an assessment of the quality of relative energies within the obtained ensembles. We demonstrated the critical role of dispersion correction within DFT computations to precisely account for weak non-bonded intramolecular interactions. By integrating anisotropic NMR analysis, chemical shifts, electronic circular dichroism, and DFT computations, we determined the absolute configurations and conformational ensembles for 1 and 2, respectively, highlighting the significance of the intramolecular methyl–π interaction in stabilizing one of the conformers. Our study introduces new strategies to address conformational flexibility in the stereochemical elucidation of challenging organic molecules.

Cytochalasans are abundant in structural diversity and potent in biological activities. Here, after the genome analysis of Curvularia verruculosa and by adding Na2S and Na2S2O3 to rice medium based on one strain-many compounds (OSMAC) strategy, we obtained and describe the characterization of six previously undescribed cytochalasans (1-6) from marine endozoic fungus Curvularia verruculosa CS-129 which was isolated from the inner fresh tissue of the deep-sea squat lobster Shinkaia crosnieri collected from the cold-seep area of the South China Sea. Among them, vercytoaspochalasin A (1) represents the first reported aspochalasin (cytochalasans biosynthesized by leucine) combining a 14-membered macrolide, while compound 3 is the first reported cytochalasan with an iodine substituent group and 20-methoxycytochalasin B γ-lactone (6) is a rare macrocyclic ring-opening natural cytochalasin coupled with a furan ring. Compounds 2, 5, 7, and 8 demonstrated differential antimicrobial efficacy against both aquatic-pathogenic bacteria and plant-pathogenic fungi with varying potency. In addition, compounds 5 and 7 could significantly inhibit the radicle growth of Amaranthus retroflexus seedlings with a dose-dependent relationship.

Marine biofouling presents a persistent challenge for maritime industries, necessitating the development of eco-friendly and intelligent antifouling strategies. In this work, an ATP-responsive nanocontainer was developed by encapsulating a natural organic compound (CS106-10), isolated from Talaromyces trachyspermus in cold seep sediments, together with D-phenylalanine (D-Phe) into ZIF-90 nanoparticles (D-Phe/CS106-10@ZIF-90). These nanoparticles were incorporated into zinc acrylate resin to fabricate a novel self-polishing antifouling coating. CS106-10, as a natural antifoulant, provided efficient and environmentally sustainable bactericidal activity, while D-Phe acted as a synergistic adjuvant to inhibit and disrupt biofilm formation. More importantly, the ATP-responsive ZIF-90 framework enabled controlled, on-demand release of antifouling agents in response to local metabolic signals associated with biofilm growth. Laboratory and real-sea evaluations confirmed that the composite coating effectively suppressed biofilm formation and significantly reduced the required dosage of conventional toxic antifoulants. This study integrates a natural antifoulant with an ATP-responsive metal–organic framework, providing new insight for developing antifouling coatings.