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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.

A large body of fungal secondary metabolites has been discovered to exhibit potent antibacterial activities with distinctive mechanisms and has the potential to be an untapped resource for drug discovery. Here, we describe the isolation and characterization of five new antibacterial indole diketopiperazine alkaloids, namely 24,25-dihydroxyvariecolorin G (1), 25-hydroxyrubrumazine B (2), 22-chloro-25-hydroxyrubrumazine B (3), 25-hydroxyvariecolorin F (4), and 27-epi-aspechinulin D (5), along with the known analogue neoechinulin B (6) from a fungal strain of deep-sea cold seep-derived Aspergillus chevalieri. Among these compounds, 3 and 4 represented a class of infrequently occurring fungal chlorinated natural products. Compounds 1–6 showed inhibitory activities against several pathogenic bacteria with MIC values ranging from 4 to 32 μg/mL. It was revealed that compound 6 could induce structural damage to the Aeromonas hydrophila cells based on the observation by scanning electron microscopy (SEM), which led to the bacteriolysis and death of A. hydrophila, suggesting that neoechinulin B (6) might be a potential alternative to novel antibiotics development.

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.

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.

Carotane sesquiterpenes are commonly found in plants but are infrequently reported in the fungal kingdom. Chemical investigation of Trichoderma virens QA-8, an endophytic fungus associated with the inner root tissue of the grown medicinal herb Artemisia argyi H. Lév. and Vaniot, resulted in the isolation and characterization of five new carotane sesquiterpenes trichocarotins I–M (1–5), which have diverse substitution patterns, and seven known related analogues (6–12). The structures of these compounds were established on the basis of a detailed interpretation of their NMR and mass spectroscopic data, and the structures including the relative and absolute configurations of compounds 1–3, 5, 9, and 10 were confirmed by X-ray crystallographic analysis. In the antibacterial assays, all isolates exhibited potent activity against Escherichia coli EMBLC-1, with MIC values ranging from 0.5 to 32 µg/mL, while 7β-hydroxy CAF-603 (7) strongly inhibited Micrococcus luteus QDIO-3 (MIC = 0.5 µg/mL). Structure-activity relationships of these compounds were discussed. The results from this study demonstrate that the endophytic fungus T. virens QA-8 from the planted medicinal herb A. argyi is a rich source of antibacterial carotane sesquiterpenes, and some of them might be interesting for further study to be developed as novel antibacterial agents.

Nine secondary metabolites (1–9), including two new polyketide derivatives 9-dehydroxysargassopenilline A (4) and 1,2-didehydropeaurantiogriseol E (5), along with seven known related secondary metabolites (1–3 and 6–9), were isolated and identified from the deep sea-derived fungus Penicilliumcyclopium SD-413. Their structures were elucidated on the basis of 1D/2D NMR spectroscopic and mass spectrometric analysis and the absolute configurations were determined by the combination of NOESY correlations and time-dependent density functional (TDDFT) ECD calculations. Compounds 1–9 inhibited some pathogenic bacteria including Escherichia coli, E. ictaluri, Edwardsiella tarda, Micrococcus luteus, Vibrio anguillarum, and V. harveyi, with MIC (minimum inhibitory concentration) values ranging from 4 to 32 μg/mL.

Secondary metabolites obtained from marine-derived fungi are rich sources of drug candidates. Three new sesquiterpenoids, chermesiterpenoids A–C (1–3), along with four known alkaloids (4–7), were isolated and identified from the marine red algal-derived fungus Penicillium chermesinum EN-480. The structures of these new sesquiterpenoids were elucidated using detailed analysis of the NMR data and their relative configurations were elucidated using nuclear overhauser effect spectroscopy (NOESY) spectra as well as gauge-independent atomic orbital (GIAO) NMR shift calculations and DP4+ probability analysis. Their absolute configurations were determined using electronic circular dichroism (ECD) calculations and modified Mosher’s method. Compounds 2 and 3 exhibited potent activities against human and aquatic pathogenic bacteria and plant pathogenic fungi.

Three new prenylated phenol derivatives, terreprenphenols A−C (1−3), along with four known related compounds (4−7), were isolated from Aspergillus terreus EN-539, an endophytic fungus obtained from the marine red alga Laurencia okamurai. The structures of these compounds were established by extensive analysis of 1D/2D NMR data, mass spectrometric data, and optical rotation (OR). The corresponding relationship between absolute configuration and optical rotation for known compounds anodendroic acid (4) and asperterreusine C (5) was ambiguous in literature, and their absolute configurations were therefore discussed and confirmed for the first time by time-dependent density functional (TDDFT) ECD and OR calculations. Compounds 1−7 inhibited some common aquatic bacteria with MIC values ranging from 2 to 64 μg/mL.

Five new polyketides, namely, 5R-hydroxyrecifeiolide (1), 5S-hydroxyrecifeiolide (2), ent-cladospolide F (3), cladospolide G (4), and cladospolide H (5), along with two known compounds (6 and 7), were isolated from the endophytic fungal strain Cladosporium cladosporioides MA-299 that was obtained from the leaves of the mangrove plant Bruguiera gymnorrhiza. The structures of these compounds were established by extensive analysis of 1D/2D NMR data, mass spectrometric data, ECDs and optical rotations, and modified Mosher’s method. The structures of 3 and 6 were confirmed by single-crystal X-ray diffraction analysis and this is the first time for reporting the crystal structures of these two compounds. All of the isolated compounds were examined for antimicrobial activities against human and aquatic bacteria and plant pathogenic fungi as well as enzymatic inhibitory activities against acetylcholinesterase. Compounds 1−4, 6, and 7 exhibited antimicrobial activity against some of the tested strains with MIC values ranging from 1.0 to 64 μg/mL, while 3 exhibited enzymatic inhibitory activity against acetylcholinesterase with the IC50 value of 40.26 μM.

Chemical investigation of the marine algal-derived endophytic fungus Aspergillus alabamensis EN-547 resulted in the isolation of 4-epi-seco-shornephine A methyl ester (1) and 4-epi-seco-shornephine A carboxylic acid (2), two new secondary metabolites having a rare diketomorpholine motif, and 28-acetoxy-12β,15α,25-trihydroxyergosta-4,6,8(14),22-tetraen-3-one (3), a new highly conjugated ergostane-type steroid, together with four known metabolites (4–7). Their chemical structures were elucidated by detailed analysis of their NMR spectra, ECDs, HRESIMS, optical rotation, and X-ray crystallographic data, and by comparison with literature data as well. The antimicrobial activities of compounds 1–7 were evaluated.