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Three sulfur-containing alkaloids aplospojaveedins A–C (1–3) with a hitherto undescribed carbon skeleton comprising octahy-dronaphthalene, α, β-unsaturated lactam and glycine-cysteine moieties were isolated from Aplosporella javeedii. Their structures were elucidated by 1D and 2D NMR spectroscopy, HR-MS, X-ray diffraction analysis, DFT-NMR and TDDFT-ECD calculations. A plausible biosynthetic pathway and putative targets are described. The blind docking suggested that 1–3 may have functional effects on several putative targets such as the GPCR cannabinoid receptor 2 or the integrin α5β1 complex.

Pseudallenes A and B (1 and 2), the new and rare examples of sulfur-containing ovalicin derivatives, along with three known analogues 3–5, were isolated and identified from the culture extract of Pseudallescheria boydii CS-793, a fungus obtained from the deep-sea cold seep sediments. Their structures were established by detailed interpretation of NMR spectroscopic and mass spectrometric data. X-ray crystallographic analysis confirmed and established the structures and absolute configurations of compounds 1–3, thus providing the first characterized crystal structure of an ovalicin-type sesquiterpenoid. In the antimicrobial assays, compounds 1–3 showed broad-spectrum inhibitory activities against several plant pathogens with MIC values ranging from 2 to 16 μg/mL.

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.

Imine reductases can catalyze reductive amination reactions to produce chiral amines, however, transformation of bulky amines has been challenging. Here, by using an increasing-molecule-volume-screening method, the authors identify a group of imine reductases that can accept bulky amines and achieve an efficient gram-scale synthesis of an API sensipar analogue.

Two new quinazolinone diketopiperazine alkaloids, including versicomide E (2) and cottoquinazoline H (4), together with ten known compounds (1, 3, and 5–12) were isolated and identified from Aspergillus versicolor AS-212, an endozoic fungus associated with the deep-sea coral Hemicorallium cf. imperiale, which was collected from the Magellan Seamounts. Their chemical structures were determined by an extensive interpretation of the spectroscopic and X-ray crystallographic data as well as specific rotation calculation, ECD calculation, and comparison of their ECD spectra. The absolute configurations of (−)-isoversicomide A (1) and cottoquinazoline A (3) were not assigned in the literature reports and were solved in the present work by single-crystal X-ray diffraction analysis. In the antibacterial assays, compound 3 exhibited antibacterial activity against aquatic pathogenic bacteria Aeromonas hydrophilia with an MIC value of 18.6 μM, while compounds 4 and 8 exhibited inhibitory effects against Vibrio harveyi and V. parahaemolyticus with MIC values ranging from 9.0 to 18.1 μM.

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.

Four unusual steckwaic acids E–H (1–4), possessing a rarely described acrylic acid unit at C-4 (1–3) or a double bond between C-12 and C-13 (4) are reported for the first time, along with four new analogues (5–8) and two known congeners (9 and 10). They were purified from the organic extract of Penicillium steckii AS-324, an endozoic fungus obtained from a deep-sea coral Acanthogorgiidae sp., which was collected from the Magellan Seamount at a depth of 1458 m. Their structures were determined by the interpretation of NMR and mass spectroscopic data. The relative and absolute configurations were determined by NOESY correlations, X-ray crystallographic analysis, and ECD calculations. All compounds were tested for their antimicrobial activities against human- and aquatic-pathogenic bacteria and plant-related pathogenic fungi.

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.

Six new metabolites, including a pair of inseparable mixtures of secofumitremorgins A (1a) and B (1b), which differed in the configuration of the nitrogen atom, 29-hydroxyfumiquinazoline C (6), 10R-15-methylpseurotin A (7), 1,4,23-trihydroxy-hopane-22,30-diol (10), and sphingofungin I (11), together with six known compounds (2–5 and 8–9), were isolated and identified from the deep-sea sediment-derived fungus Aspergillus fumigatus SD-406. Their structures were determined by detailed spectroscopic analysis of NMR and MS data, chiral HPLC analysis of the acidic hydrolysate, X-ray crystallographic analysis, J-based configuration analysis, and quantum chemical calculations of ECD, OR, and NMR (with DP4+ probability analysis). Among the compounds, 1a/1b represent a pair of novel scaffolds derived from indole diketopiperazine by cleavage of the amide bond following aromatization to give a pyridine ring. Compounds 1, 4, 6, 7, 10 and 11 showed inhibitory activities against pathogenic bacteria and plant pathogenic fungus, with MIC values ranging from 4 to 64 μg/mL.

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.

Deep sea has an extreme environment which leads to biodiversity of microorganisms and their unique physical and biochemical mechanisms. Deep-sea derived microorganisms are more likely to produce novel bioactive substances with special mechanism of action for drug discovery. This article reviews secondary metabolites with biological activities such as anti-tumor, anti-bacterial, anti-viral, and anti-inflammatory isolated from deep-sea fungi and bacteria during 2018–2020. Effective methods for screening and obtaining natural active compounds from deep-sea microorganisms are also summarized, including optimizing the culture conditions, using genome mining technology, biosynthesis and so on. The comprehensive application of these methods makes broader prospects for the development and application of deep sea microbial bioactive substances.

Three new phenylhydrazones, penoxahydrazones A–C (compounds 1–3), and two new quinazolines, penoxazolones A (compound 4) and B (compound 5), with unique linkages were isolated from the fungus Penicillium oxalicum obtained from the deep sea cold seep. Their structures and relative configurations were assigned by analysis of 1D/2D NMR and mass spectroscopic data, and the absolute configurations of 1, 4, and 5 were established on the basis of X-ray crystallography or ECD calculations. Compound 1 represents the first natural phenylhydrazone-bearing steroid, while compounds 2 and 3 are rarely occurring phenylhydrazone tautomers. Compounds 4 and 5 are enantiomers that feature quinazoline and cinnamic acid units. Some isolates exhibited inhibition of several marine phytoplankton species and marine-derived bacteria.

A new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative, varioloid A (1), was isolated from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291. Its structure was elucidated on the basis of extensive analysis of 1D and 2D NMR data and the absolute configuration was determined by time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations. A similar compound, whose planar structure was previously described but the relative and absolute configurations and 13C NMR data were not reported, was also identified and was tentatively named as varioloid B (2). Both compounds 1 and 2 exhibited cytotoxicity against A549, HCT116, and HepG2 cell lines, with IC50 values ranging from 2.6 to 8.2 µg/mL.

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.

The co-cultivation of two or more different microbial strains in one culture vessel was supposed to be a viable experimental approach for enhancing the diversity of the compounds produced. Two new meroterpenoid derivatives, chermebilaenes A (1) and B (2), together with three known sesquiterpenoids, sesquicaranoic acid B (3), cyclonerodiol (4) and bisabol-l-on-13-säuremethylester (5), were characterized from a co-culture of the marine-derived fungal isolates of Penicillium bilaiae MA-267 and Penicillium chermesinum EN-480. Neither fungus produced these compounds when cultured alone under the same conditions. Compound 1 represents an unprecedented acorane-type sesquiterpene hybridized with an octadecadienoic acid skeleton. The structures were elucidated on the basis of spectroscopic analysis, and the absolute configurations were assumed on the basis of acidic hydrolysis combined with modified Mosher’s method and electronic circular dichroism (ECD) calculations. Compound 1 showed potent inhibitory activities against Ceratobasidium cornigerum and Edwardsiella tarda.

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.

Four new thiodiketopiperazine alkaloids, namely, 5’-hydroxy-6’-ene-epicoccin G (1), 7-methoxy-7’-hydroxyepicoccin G (2), 8’-acetoxyepicoccin D (3), and 7’-demethoxyrostratin C (4), as well as a pair of new enantiomeric diketopiperazines, (±)-5-hydroxydiphenylalazine A (5), along with five known analogues (6−10), were isolated and identified from the culture extract of Epicoccum nigrum SD-388, a fungus obtained from deep-sea sediments (−4500 m). Their structures were established on the basis of detailed interpretation of the NMR spectroscopic and mass spectrometric data. X-ray crystallographic analysis confirmed the structures and established the absolute configurations of compounds 1−3, while the absolute configurations for compounds 4 and 5 were determined by ECD calculations. Compounds 4 and 10 showed potent activity against Huh7.5 liver tumor cells, which were comparable to that of the positive control, sorafenib, and the disulfide bridge at C-2/C-2’ is likely essential for the activity.

The potential anti-tumor agent wentilactones were produced by a newly isolated marine fungus Aspergillus dimorphicus. This fungus was derived from deep-sea sediment and identified by polyphasic approach, combining phenotypic, molecular, and extrolite profiles. However, wentilactone production was detected only under static cultures with very low yields. In order to improve wentilactone production, culture conditions were optimized using the response surface methodology. Under the optimal static fermentation conditions, the experimental values were closely consistent with the prediction model. The yields of wentilactone A and B were increased about 11-fold to 13.4 and 6.5 mg/L, respectively. The result was further verified by fermentation scale-up for wentilactone production. Moreover, some small-molecule elicitors were found to have capacity of stimulating wentilactone production. To our knowledge, this is first report of optimized production of tetranorlabdane diterpenoids by a deep-sea derived marine fungus. The present study might be valuable for efficient production of wentilactones and fundamental investigation of the anti-tumor mechanism of norditerpenoids.

Peniciadametizine A (1); a new dithiodiketopiperazine derivative possessing a unique spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] skeleton, together with a highly oxygenated new analogue, peniciadametizine B (2); as well as two known compounds, brasiliamide A (3); and viridicatumtoxin (4), were isolated and identified from Penicillium adametzioides AS-53, a fungus obtained from an unidentified marine sponge. The unambiguous assignment of the relative and absolute configuration for the spiro center C-2 of compound 1 was solved by the combination of NMR and ECD measurements with Density-Functional Theory (DFT) conformational analysis and Time-Dependent Density-Functional Theory-Electronic Circular Dichroism (TDDFT-ECD) calculations. The spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] skeleton of 1 has not been reported yet among natural products and the biosynthetic pathway for 1 and 2 was discussed. Compounds 1 and 2 showed inhibitory activity against the pathogenic fungus Alternaria brassicae.

Five new sulfide diketopiperazine derivatives, namely, penicibrocazines A–E (1–5), along with a known congener (6), were isolated and identified from the culture extract of Penicillium brocae MA-231, an endophytic fungus obtained from the fresh tissue of the marine mangrove plant Avicennia marina. The structures of these compounds were elucidated by detailed interpretation of NMR and mass spectroscopic data and the structures of compounds 1 and 3 were confirmed by single-crystal X-ray diffraction analysis. All these compounds were examined for cytotoxic and antimicrobial activities. Compounds 2–6 exhibited antimicrobial activity against some of the tested strains with MIC values ranging from 0.25 to 64 μg/mL.

The first total synthesis of marine-derived penicimonoterpene (±)-1 has been achieved in four steps from 6-methylhept-5-en-2-one using a Reformatsky reaction as the key step to construct the basic carbon skeleton. A total of 24 new derivatives of 1 have also been designed and synthesized. Their structures were characterized by analysis of their 1H NMR, 13C NMR and HRESIMS data. Some of them showed significant antibacterial activity against Aeromonas hydrophila, Escherichia coli, Micrococcus luteus, Staphylococcus aureus, Vibrio anguillarum, V. harveyi and/or V. parahaemolyticus, and some showed activity against plant-pathogenic fungi (Alternaria brassicae, Colletotrichum gloeosporioides and/or Fusarium graminearum). Some of the derivatives exhibited antimicrobial MIC values ranging from 0.25 to 4 μg/mL, which were stronger than those of the positive control. Notably, Compounds 3b and 10 showed extremely high selectively against plant-pathogenic fungus F. graminearum (MIC 0.25 μg/mL) and pathogenic bacteria E. coli (MIC 1 μg/mL), implying their potential as antimicrobial agents. SAR analysis of 1 and its derivatives indicated that modification of the carbon-carbon double bond at C-6/7, of groups on the allylic methylene unit and of the carbonyl group at C-1, effectively enhanced the antimicrobial activity.

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.

Three new indolediketopiperazine peroxides, namely, 24-hydroxyverruculogen (1), 26-hydroxyverruculogen (2), and 13-O-prenyl-26-hydroxyverruculogen (3), along with four known homologues (4–7), were isolated and identified from the culture extract of the marine sediment-derived fungus Penicillium brefeldianum SD-273. Their structures were determined based on the extensive spectroscopic analysis and compound 1 was confirmed by X-ray crystallographic analysis. The absolute configuration of compounds 1–3 was determined using chiral HPLC analysis of their acidic hydrolysates. Each of the isolated compounds was evaluated for antibacterial and cytotoxic activity as well as brine shrimp (Artemia salina) lethality.

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.

Two new antimicrobial bisabolane-type sesquiterpenoid derivatives, ent-aspergoterpenin C (compound 1) and 7-O-methylhydroxysydonic acid (2), and two new butyrolactone-type monoterpenoids, pestalotiolactones C (3) and D (4), along with a known monoterpenoid pestalotiolactone A (5) and four known bisabolane sesquiterpenoids (6−9), were isolated and identified from the deep-sea sediment-derived fungus Aspergillus versicolor SD-330. The structures of these compounds were elucidated on the basis of spectroscopic analysis, and the absolute configurations of the new compounds 1−4 were determined by the combination of NOESY and TDDFT-ECD calculations and X-ray crystallographic analysis. Additionally, we first determined and reported the absolute configuration of the known monoterpenoid pestalotiolactone A (5) through the X-ray crystallographic experiment. All of these isolated compounds were evaluated for antimicrobial activities against human and aquatic pathogenic bacteria. Compounds 1, 2, 6 and 9 exhibited selective inhibitory activities against zoonotic pathogenic bacteria such as Escherichia coli, Edwardsiella tarda, Vibrio anguillarum and V. harveyi, with MIC values ranging from 1.0 to 8.0 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.

An endophytic fungus Arthrinium arundinis TE-3 was isolated and purified from the fresh leaves of cultivated tobacco (Nicotiana tabacum L.). Chemical investigation on this fungal strain afforded three new prenylated diphenyl ethers (1⁻3) as well as three known analogues (4⁻6). Structure elucidation of the isolated compounds was carried out by analysis of 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS) spectra, as well as by comparison of those data with literature data. The absolute configuration of the stereogenic center at C-8 in 1 was assigned by comparison of the experimental and calculated ECD spectra. Compounds 1 and 2 showed selective antifungal activity against Mucor hiemalis with minimum inhibitory concentration (MIC) values of 8 and 4 μg/mL, respectively. Compounds 5 and 6 exhibited inhibitory activity against Alteraria alternata with an MIC value of 8 μg/mL. In the cytotoxic assay, 2, 5, and 6 displayed moderate in vitro cytotoxicity against the human monocytic cell line (THP-1 cell line), with IC50 values of 40.2, 28.3, and 25.9 μM, respectively. This study indicated that endophytic fungi possess great potential for exploring new bioactive secondary metabolites.

Wentiquinone C, which was previously isolated from the marine brown alga-derived endophytic fungus Aspergillus wentii EN-48, was found to be a potent antioxidant against α,α-diphenyl-picrylhydrazyl (DPPH) radical. The structure of wentiquinone C was originally assigned as an anthraquinone derivative (1,10-dihydroxy-3-(hydroxymethyl)-8-methoxydibenzo [b,e]oxepine-6,11-dione, 1) by 1D and 2D NMR experiments. However, the minor differences of the chemical shifts between xanthones and anthraquinones were queried, leading to the structure of 1 to be revised as a xanthone analog (8-hydroxy-6-(hydroxymethyl)-3-methoxy-9-oxo-9H-xanthene-1-carboxylic acid, 2) on the basis of a methylation and subsequent NMR measurements, and was confirmed by X-ray crystallographic analysis. The method established in this paper could be applied to the structural re-examination or revision for some of the reported seco-anthraquinone derivatives.

Five new anthranilic acid derivatives, penipacids A–E (1–5), together with one known analogue (6), which was previously synthesized, were characterized from the ethyl acetate extract of the marine sediment-derived fungus Penicillium paneum SD-44. Their structures were elucidated mainly by extensive NMR spectroscopic and mass spectrometric analysis. The cytotoxicity and antimicrobial activity of the isolated compounds were evaluated. Compounds 1, and 5 exhibited inhibitory activity against human colon cancer RKO cell line, while compound 6 displayed cytotoxic activity against Hela cell line.

Four new quinazolinone alkaloids, namely, aniquinazolines A–D (1–4), were isolated and identified from the culture of Aspergillus nidulans MA-143, an endophytic fungus obtained from the leaves of marine mangrove plant Rhizophora stylosa. The structures of the new compounds were elucidated by spectroscopic analysis, and their absolute configurations were determined on the basis of chiral HPLC analysis of the acidic hydrolysates. The structure for 1 was confirmed by single-crystal X-ray diffraction analysis. All these compounds were examined for antibacterial and cytotoxic activity as well as brine shrimp (Artemia salina) lethality.

Two new secondary metabolites, namely, pinodiketopiperazine A (1) and 6,7-dihydroxy-3-methoxy-3-methylphthalide (2), along with alternariol 2,4-dimethyl ether (3) and l-5-oxoproline methyl ester (4), which were isolated from a natural source for the first time but have been previously synthesized, were characterized from the marine sediment-derived fungus Penicillium pinophilum SD-272. In addition, six known metabolites (5–10) were also identified. Their structures were elucidated by analysis of the NMR and mass spectroscopic data. The absolute configuration of compound 1 was determined by experimental and calculated ECD spectra. Compound 2 displayed potent brine shrimp (Artemia salina) lethality with LD50 11.2 μM.

In addition to 13 known compounds, four new bisabolane sesquiterpenes, okamurenes A–D (1–4), a new chamigrane derivative, okamurene E (5), and a new C12-acetogenin, okamuragenin (6), were isolated from the marine red alga Laurencia okamurai. The structures of these compounds were determined through detailed spectroscopic analyses. Of these, okamurenes A and B (1 and 2) are the first examples of bromobisabolane sesquiterpenes possessing a phenyl moiety among Laurencia-derived sesquiterpenes, while okamuragenin (6) was the first acetogenin aldehyde possessing a C12-carbon skeleton. Each of the isolated compounds was evaluated for the brine shrimp (Artemia salina) lethal assay and 7-hydroxylaurene displayed potent lethality with LD50 1.8 μM.

Halogenated natural products are widespread in the environment, and the halogen atoms are typically vital to their bioactivities. Thus far, six families of halogenating enzymes have been identified: cofactor-free haloperoxidases (HPO), vanadium-dependent haloperoxidases (V-HPO), heme iron-dependent haloperoxidases (HI-HPO), non-heme iron-dependent halogenases (NI-HG), flavin-dependent halogenases (F-HG), and S-adenosyl-L-methionine (SAM)-dependent halogenases (S-HG). However, these halogenating enzymes with similar biological functions but distinct structures might have evolved independently. Phylogenetic and structural analyses suggest that the HPO, V-HPO, HI-HPO, NI-HG, F-HG, and S-HG enzyme families may have evolutionary relationships to the α/β hydrolases, acid phosphatases, peroxidases, chemotaxis phosphatases, oxidoreductases, and SAM hydroxide adenosyltransferases, respectively. These halogenating enzymes have established sequence homology, structural conservation, and mechanistic features within each family. Understanding the distinct evolutionary history of these halogenating enzymes will provide further insights into the study of their catalytic mechanisms and halogenation specificity.

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.

Four new uncommon 20-nor-isopimarane diterpenoid epimers, aspewentins I−L (1⁻4), together with a new methylated derivative of 3, aspewentin M (5), were isolated from the deep sea sediment-derived fungus Aspergillus wentii SD-310. The very similar structures of these epimers made the separation and purification procedures difficult. The structures of compounds 1⁻5 were illustrated based on spectroscopic analysis, and the absolute configurations of compounds 1⁻5 were unambiguously determined by the combination of NOESY, time-dependent density functional (TDDFT)-ECD calculations, and X-ray crystallographic analysis. These metabolites represented the rare examples of 20-nor-isopimarane analogues possessing a cyclohexa-2,5-dien-1-one moiety. These compounds were tested for antimicrobial activities against human and aquatic pathogenic bacteria, as well as plant-pathogenic fungi. While compounds 1 and 2 exhibited inhibitory activities against zoonotic pathogenic bacteria such as Escherichia coli, Edwardsiella tarda, Vibrio harveyi, and V. parahaemolyticus, compound 5 showed potent activity against the plant pathogen Fusarium graminearum.

Cultivation of the endophytic fungus Penicillium commune, which was isolated from the semi-mangrove plant Hibiscus tiliaceus,afforded one new compound 1-O-(2,4-dihydroxy-6-methylbenzoyl)-glycerol (1) along with thirteen known products, including 1-O-acetylglycerol (2), N-acetyltryptophan (3), 3-indolylacetic acid methyl ester (4), 1-(2,4-dihydroxy-3,5-dimethylphenyl)ethanone (5), 2-(2,5-dihydroxyphenyl)acetic acid (6), (4R,5S)-5-hydroxyhexan-4-olide (7), thymidine (8), uracil (9), thymine (10), ergosterol (11), β-sitosterol (12),β-daucosterol (13), and ergosta-7,22-dien-3β,5α,6β-triol (14). The structures of these compounds were established by detailed NMR spectroscopic analysis, as well as by comparison with literature data or with authentic samples.

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.

Two new brominated selinane sesquiterpenes, 1-bromoselin-4(14),11-diene (1) and 9-bromoselin-4(14),11-diene (2), one known cadinane sesquiterpene, cadalene (3), and four known selinane sesquiterpenes, α-selinene (4), β-selinene (5), β-dictyopterol (6), and cyperusol C (7), were isolated from a sample of marine brown alga Dictyopteris divaricata collected off the coast of Yantai (China). Their structures were established by detailed MS and NMR spectroscopic analysis, as well as comparison with literature data.

A sample of the marine brown alga D. divaricata collected off the coast of Yantai (P.R. China) was dried, powdered, and extracted with the mixture of CHCl3 and MeOH (1:1, v/v). By a combination of silica gel and Sephadex LH-20 column chromatography and preparative TLC, a new cadinane sesquiterpene 1,4-epoxymuurolan-5β-ol (1) was isolated from this species. Its structure was established by detailed MS and NMR spectroscopic analysis, as well as comparison with literature data.

Seven parguerane diterpenes: 15-bromo-2,7,19-triacetoxyparguer-9(11)-en-16-ol (1), 15-bromo-2,7,16,19-tetraacetoxyparguer-9(11)-ene (2), 15-bromo-2,19-diacetoxyparguer-9(11)-en-7,16-diol (3), 15-bromo-2,16,19-triacetoxyparguer-9(11)-en-7-ol (4), 15-bromo-2,16-diacetoxyparguer-9(11)-en-7-ol (5), 15-bromoparguer-9(11)-en-16-ol (6), 15-bromoparguer-7-en-16-ol (7), two polyether triterpenes: thyrsiferol (8) and thyrsiferyl 23-acetate (9), and one C15-acetogenin, neolaurallene (10), were isolated from a sample of marine red alga Laurencia saitoi collected off the coast of Yantai. Their structures were established by detailed NMR spectroscopic analysis and comparison with literature data.

A new acetylated flavanol, 3,7-O-diacetyl (–)-epicatechin (3), and seven known flavanol derivatives, (–)-epicatechin (1), 3-O-acetyl (–)-epicatechin (2), 3,3′,4′,5,7-O-pentaacetyl (–)-epicatechin (4), (+)-afzelechin (5), (+)-catechin (6), cinchonain Ib (7), and proanthocyanidin B2 (8), were isolated from the stems and twigs of the mangrove plant Rhizophora stylosa and identified. The crude extract, the different fractions and all of the purified compounds were evaluated for DPPH radical scavenging activity.

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.

Two new diphenylketones (1 and 2), a new xanthone (3), and a known xanthone analogue (4) were isolated and identified from Talaromyces islandicus EN-501, an endophytic fungus obtained from the fresh collected marine red alga Laurencia okamurai. Their structures were elucidated on the basis of NMR spectroscopic and X-ray crystallographic analysis. The joint isolation of benzophenones and xanthones from the same fungal strain supports the biogenesis of xanthones via a benzophenone intermediate. It is worth mentioning that xanthones 3 and 4 have a methyl group at C-6 and C-2, respectively, which is uncommon compared with typical xanthones usually having a methyl group at C-8. Compounds 1–4 exhibited potent antioxidative activities against DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonate) radicals with IC50 values ranging from 0.58 to 6.92 μg/mL, which are stronger than that of the positive controls BHT (butylated hydroxytoluene) and ascorbic acid. Compounds 1, 3, and 4 also showed inhibitory activities against several pathogenic bacteria.