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Biofilms represent a key challenge in the treatment of microbial infections; for instance, Staphylococcus aureus causes chronic or fatal infections by forming biofilms on medical devices. Herein, the fungus Arcopilus navicularis was found to produce a novel family of PKS-NRPS metabolites that are able to disrupt preformed biofilms of S. aureus . Arcopilins A-F ( 1 - 6 ), tetramic acids, and arcopilin G ( 7 ), a 2-pyridone, were elucidated using HR-ESI-MS and one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy. Their absolute configuration was established by the synthesis of MPTA-esters for 2 , analysis of 1 H- 1 H coupling constants, and ROESY correlations, along with comparison with the crystal structure of 7 . Arcopilin A ( 1 ) not only effectively disrupts preformed biofilms of S. aureus but also potentiates the activity of gentamicin and vancomycin up to 115- and 31-fold times, respectively. Our findings demonstrate the potential application of arcopilins for the conjugated treatment of infections caused by S. aureus with antibiotics unable to disrupt preformed biofilms.

Ash dieback, caused by the fungal pathogen Hymenoscyphus fraxineus (Helotiales, Ascomycota) , is threatening the existence of the European ash, Fraxineus excelsior . During our search for biological control agents for this devastating disease, endophytic fungi were isolated from healthy plant tissues and co-cultivated with H. fraxineus to assess their antagonistic potential. Among the strains screened, Penicillium cf. manginii DSM 104493 most strongly inhibited the pathogen. Initially , DSM 104493 showed promise in planta as a biocontrol agent. Inoculation of DSM 104493 into axenically cultured ash seedlings greatly decreased the development of disease symptoms in seedlings infected with H. fraxineus . The fungus was thus cultivated on a larger scale in order to obtain sufficient material to identify active metabolites that accounted for the antibiosis observed in dual culture. We isolated PF1140 (1) and identified it as the main active compound in the course of a bioassay-guided isolation strategy. Furthermore, its derivative 2, the mycotoxin citreoviridin (3), three tetramic acids of the vancouverone type (4-6), and penidiamide (7) were isolated by preparative chromatography. The structures were elucidated mainly by NMR spectroscopy and high-resolution mass spectrometry (HRMS), of which compounds 2 and 6 represent novel natural products. Of the compounds tested, not only PF1140 (1) strongly inhibited H. fraxineus in an agar diffusion assay but also showed phytotoxic effects in a leaf puncture assay. Unfortunately, both the latent virulent attributes of DSM 104493 observed subsequent to these experiments in planta and the production of mycotoxins exclude strain Penicillium cf. manginii DSM 104493 from further development as a safe biocontrol agent.IMPORTANCEEnvironmentally friendly measures are urgently needed to control the causative agent of ash dieback, Hymenoscyphus fraxineus . Herein, we show that the endophyte DSM 104493 exhibits protective effects in vitro and in planta . We traced the activity of DSM 104493 to the antifungal natural product PF1140, which unfortunately also showed phytotoxic effects. Our results have important implications for understanding plant-fungal interactions mediated by secondary metabolites, not only in the context of ash dieback but also generally in plant-microbial interactions., Competing Interests: The authors declare no conflict of interest.

In this investigation, we explored the diversity of melleolide-type meroterpenoids produced by Armillaria ostoyae, one of the largest and oldest organisms on Earth, using extracts from liquid and solid fermentation media. The study unveiled three unprecedented dimeric bismelleolides and three novel fatty-acid-substituted congeners, along with 11 new and 21 known derivatives. The structures were elucidated by 1D and 2D NMR spectroscopy and HRESI-MS, and ROESY spectral analysis for relative configurations. Absolute configurations were determined from crystal structures and through ECD spectra comparison. A compound library of melleolide-type meroterpenoids facilitated metabolomics-wide associations, revealing production patterns under different culture conditions. The library enabled assessments of antimicrobial and cytotoxic activities, revealing that the Δ 2,4 double bond is not crucial for antifungal activity. Cytotoxicity was linked to the presence of an aldehyde at C1, but lost with hydroxylation at C13. Chemoinformatic analyses demonstrated the intricate interplay of chemical modifications on biological properties. This study marks the first systematic exploration of Armillaria spp. meroterpenoid diversity by MS-based untargeted metabolomics, offering insight into structure-activity relationships through innovative chemoinformatics., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Importance: The integration of metabolomics-based approaches into the discovery pipeline has enabled improved mining and prioritization of prolific secondary metabolite producers such as endophytic fungi. However, relying on automated untargeted analysis tools might lead to misestimation of the chemical complexity harbored in these organisms. Our study emphasizes the importance of isolation and structure elucidation of the respective metabolites in addition to deep metabolome analysis for the correct interpretation of untargeted metabolomics approaches such as molecular networking. Additionally, it encourages the further exploration of endophytic fungi from traditional medicinal plants for the discovery of natural products., Competing Interests: The authors declare no conflict of interest.

Metabolites 1 and 2 , isolated from cultures of the basidiomycete Resupinatus sp. BCC84615, collected in a tropical forest in northeastern Thailand, showed weak antibiotic activity against Bacillus subtilis and Staphylococcus aureus and cytotoxicity against cancer cell lines. Their planar structures were elucidated by high-resolution electrospray ionization mass spectrometry and NMR spectroscopy as clavilactone J, known from the basidiomycete Ampulloclitocybe clavipes , and its new 1,4-benzoquinone derivative. A detailed analysis of the ROESY correlations in 1 confirmed the recent revision of the relative configuration of clavilactone J. However, specific rotation and Cotton effects observed by electronic circular dichroism were contrary to those of the clavilactones; thus, we assigned a rare antipodal absolute configuration.

A fungal endophyte originating from the Canary Islands was identified as a potent antagonist against the fungal phytopathogen Hymenoscyphus fraxineus , which causes the devastating ash dieback disease. This endophyte was tentatively identified as Pezicula cf. ericae , using molecular barcoding. Isolation of secondary metabolites by preparative high-performance liquid chromatography (HPLC) yielded the known compounds CJ-17,572 ( 1 ), mycorrhizin A ( 3 ) and cryptosporioptides A-C ( 4 - 6 ), besides a new N -acetylated dihydroxyphenylalanin derivative 2 , named peziculastatin. Planar structures were elucidated by NMR and HRMS data, while the relative stereochemistry of 2 was assigned by H,H and C,H coupling constants. The assignment of the unknown stereochemistry of CJ-17,572 ( 1 ) was hampered by the broadening of NMR signals. Nevertheless, after semisynthetic conversion of 1 into its methyl derivatives 7 and 8 , presumably preventing tautomeric effects, the relative configuration could be assigned, whereas comparison of ECD data to those of related compounds determined the absolute configuration. Metabolites 1 and 3 showed significant antifungal effects in vitro against H. fraxineus . Furthermore, 4 - 6 exhibited significant dispersive effects on preformed biofilms of S. aureus at concentrations up to 2 µg/mL, while the biofilm formation of C. albicans was also inhibited. Thus, cryptosporioptides might constitute a potential source for the development of novel antibiofilm agents.

Streptogramins are the last line of defense antimicrobials with pristinamycin as a representative substance used as therapeutics against highly resistant pathogenic bacteria. However, the emergence of (multi)drug-resistant pathogens renders these valuable antibiotics useless; making it necessary to derivatize compounds for new compound characteristics, which is often difficult by chemical de novo synthesis due to the complex nature of the molecules. An alternative to substance derivatization is mutasynthesis. Herein, we report about a mutasynthesis approach, targeting the phenylglycine (Phg) residue for substance derivatization, a pivotal component of streptogramin antibiotics. Mutasynthesis with halogenated Phg(-like) derivatives altogether led to the production of two new derivatized natural compounds, as there are 6-chloropristinamycin I and 6-fluoropristinamycin I based on LC-MS/MS analysis. 6-Chloropristinamycin I and 6-fluoropristinamycin I were isolated by preparative HPLC, structurally confirmed using NMR spectroscopy and tested for antimicrobial bioactivity. In a whole-cell biotransformation approach using an engineered E. coli BL21(DE3) pET28- hmo /pACYC- bcd-gdh strain, Phg derivatives were generated fermentatively. Supplementation with the E. coli biotransformation fermentation broth containing 4-fluorophenylglycine to the pristinamycin mutasynthesis strain resulted in the production of 6-fluoropristinamycin I, demonstrating an advanced level of mutasynthesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (This journal is © The Royal Society of Chemistry.)

From a fresh root of Trema guineensis (Ulmaceae), endophytic fungi were isolated, among which a taxon belonging to the new species Diaporthe cameroonensis . This strain was fermented in shake flask batch cultures and the broth was extracted with ethyl acetate. From the crude extract, a hemiketal polyketide 1 , and an acetylated alternariol 2 were isolated, along with fifteen known secondary metabolites. Their structures were established by extensive NMR spectroscopy and mass spectrometry analyses, as well as by comparison with literature data of their analogs., (Copyright © 2023, Mountessou et al.)

The structure of the SARS-CoV-2 spike RBD and human ACE2 as well as changes in the structure due to binding activities were analysed using surface enhanced Raman spectroscopy. The inhibitor cohaerin C was applied to inhibit the binding between spike RBD and ACE2. Differences and changes in the Raman spectra were determined using deconvolution of the amide bands and principal component analysis. We thus demonstrate a fast and label-free analysis of the protein structures and the differentiation between bound and unbound states. The approach is suitable for sensing and screening and might be relevant to investigate other protein systems as well., Competing Interests: The authors declare no conflicts of interest., (Published by Optica Publishing Group under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)

The recent description of the putative fungal pathogen of greenheart trees, Xylaria karyophthora (Xylariaceae, Ascomycota), prompted a study of its secondary metabolism to access its ability to produce cytochalasans in culture. Solid-state fermentation of the ex-type strain on rice medium resulted in the isolation of a series of 19,20-epoxidated cytochalasins by means of preparative high-performance liquid chromatography (HPLC). Nine out of 10 compounds could be assigned to previously described structures, with one compound being new to science after structural assignment via nuclear magnetic resonance (NMR) assisted by high-resolution mass spectrometry (HRMS). We propose the trivial name "karyochalasin" for the unprecedented metabolite. The compounds were used in our ongoing screening campaign to study the structure-activity relationship of this family of compounds. This was done by examining their cytotoxicity against eukaryotic cells and impact on the organization of networks built by their main target, actin-a protein indispensable for processes mediating cellular shape changes and movement. Moreover, the cytochalasins' ability to inhibit the biofilm formation of Candida albicans and Staphylococcus aureus was examined.

With heimionones A-E ( 1 - 5 ), five new terpenoids were isolated from submerged cultures of Heimiomyces sp. in addition to the previously described compounds hispidin, hypholomin B, and heimiomycins A and B. Planar structures of the metabolites were elucidated by 1D and 2D NMR in addition to HRESIMS data. While ROESY data assigned relative configurations, absolute configurations were determined by the synthesis of MTPA esters of 1 , 3 , and 5 . The [6.3.0] undecane core structure of compounds 3 - 5 is of the asteriscane-type, however, the scaffold of 1 and 2 with their bicyclo [5.3.0] decane core and germinal methyl substitution is, to our knowledge, unprecedented. Together with several new compounds that were previously isolated from solid cultures of this strain, Heimiomyces sp. showed an exceptionally high chemical diversity of its secondary metabolite profile.

During a study of the diversity of soilborne fungi from Spain, a strain belonging to the family Chaetomiaceae (Sordariales) was isolated. The multigene phylogenetic inference using five DNA loci showed that this strain represents an undescribed species of the genus Amesia , herein introduced as A. hispanica sp. nov. Investigation of its secondary metabolome led to the isolation of two new derivatives ( 2 and 3 ) of the known antifungal antibiotic dactylfungin A ( 1 ), together with the known compound cochliodinol ( 4 ). The planar structures of 1 - 4 were determined by ultrahigh performance liquid chromatography coupled with diode array detection and ion mobility tandem mass spectrometry (UHPLC-DAD-IM-MS/MS) and extensive 1D and 2D nuclear magnetic resonance (NMR) spectroscopy after isolation by HPLC. All isolated secondary metabolites were tested for their antimicrobial and cytotoxic activities. Dactylfungin A ( 1 ) showed selective and strong antifungal activity against some of the tested human pathogens ( Aspergillus fumigatus and Cryptococcus neoformans ). The additional hydroxyl group in 2 resulted in the loss of activity against C. neoformans but still retained the inhibition of As. fumigatus in a lower concentration than that of the respective control, without showing any cytotoxic effects. In contrast, 25″-dehydroxy-dactylfungin A ( 3 ) exhibited improved activity against yeasts ( Schizosaccharomyces pombe and Rhodotorula glutinis ) than 1 and 2 , but resulted in the appearance of slight cytotoxicity. The present study exemplifies how even in a well-studied taxonomic group such as the Chaetomiaceae, the investigation of novel taxa still brings chemistry novelty, as demonstrated in this first report of this antibiotic class for chaetomiaceous and sordarialean taxa.

New meroterpenoids bis-heimiomycins A-D ( 1 - 4 ) and heimiomycins D and E ( 5 and 6 ) were isolated from solid rice cultures of Heimiomyces sp., while new calamene-type sesquiterpenoids heimiocalamene A ( 7 ) and B ( 8 ) were isolated from shake cultures, respectively. Structures of the metabolites were elucidated by 1D and 2D NMR in addition to HRESIMS data. While relative configurations were assigned by ROESY data, absolute configurations were derived from the structurally related, previously described calamenes, which we herein name heimiocalamenes C-E ( 9 - 11 ). A plausible biosynthetic pathway was proposed for 1 - 6 , with a radical reaction connecting their central para -benzoquinone building block to calamene-sesquiterpenoids. Based on the assumption of a common biosynthesis, we reviewed the structure of the known nitrogen-containing derivative 11 , calling the validity of the originally proposed structure into question. Subsequently, the structure of 11 was revised by analysis of HMBC and ROESY NMR data. Only heimiomycin D ( 5 ) displayed cytotoxic effects against cell line KB3.1.

Protein microarray screenings identified fungal natural products from the azaphilone family as potent inhibitors of SARS-CoV-2 spike protein binding to host ACE2 receptors. Cohaerin F, as the most potent substance from the cohaerin group, led to more than 50% less binding of ACE2 and SARS-CoV-2 spike protein. A survey for structurally related azaphilones yielded the structure elucidation of six new multiformins E-J ( 10 - 15 ) and the revision of the stereochemistry of the multiformins. Cohaerin and multiformin azaphilones (1-5, 8 , 12 ) were assessed for their activity in a cell-based infection assay. Calu-3 cells expressing human ACE2 receptor showed more than 75% and 50% less infection by SARS-CoV-2 pseudotyped lentivirus particles after treatment with cohaerin C (1) and cohaerin F ( 4 ), respectively. Multiformin C ( 8 ) and G ( 12 ) that nearly abolished the infection of cells. Our data show that multiformin-type azaphilones prevent the binding of SARS-CoV-2 to the cell entry receptor ACE2.

Five new drimane-type sesquiterpenoids were isolated from cultures of the tropical basidiomycetes, Perenniporia centrali-africana (originating from Kenya) and Cerrena sp. nov. (originating from Thailand). A new pereniporin A derivative ( 1 ), a new drimane-type sesquiterpene lactam ( 2 ), and the new 6,7-Dehydro-isodrimenediol ( 3 ) were isolated from P. centrali-africana. In parallel, the two new drimane-type sesquiterpene lactams 5 and 6 were isolated together with known isodrimenediol ( 4 ) from Cerrena sp. This is the first report of drimane-type sesquiterpene lactams from basidiomycetes. The structures were elucidated based on 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data, in combination with high-resolution electrospray mass spectrometric (HR-ESIMS) data. The compounds were devoid of significant antimicrobial and cytotoxic activities.

Laying the groundwork on preliminary structure-activity relationship study relating to the disruptive activity of cytochalasan derivatives on mammalian cell actin cytoskeleton, we furthered our study on the cytochalasans of the Dothideomycetes fungus, Sparticola triseptata . A new cytochalasan analog triseptatin ( 1 ), along with the previously described cytochalasans deoxaphomin B ( 2 ) and cytochalasin B ( 3 ), and polyketide derivatives cis -4-hydroxy-6-deoxyscytalone ( 4 ) and 6-hydroxymellein ( 5 ) were isolated from the rice culture of S. triseptata . The structure of 1 was elucidated through NMR spectroscopic analysis and high-resolution mass spectrometry (HR-ESI-MS). The relative and absolute configurations were established through analysis of NOESY spectroscopic data and later correlated with experimental electronic circular dichroism and time-dependent density functional theory (ECD-TDDFT) computational analysis. Compounds 1 and 2 showed cytotoxic activities against seven mammalian cell lines (L929, KB3.1, MCF-7, A549, PC-3, SKOV-3, and A431) and antiproliferative effects against the myeloid leukemia K-562 cancer cell line. Both 1 and 2 were shown to possess properties inhibiting the F-actin network, prompting further hypotheses that should to be tested in the future to enable a well-resolved concept of the structural implications determining the bioactivity of the cytochalasin backbone against F-actin.

The soil microbiome comprises numerous filamentous fungi and bacteria that mutually react and challenge each other by the production of bioactive secondary metabolites. Herein, we show in liquid co-cultures that the presence of filamentous Streptomycetes producing antifungal glycopeptide antibiotics induces the production of the antibacterial and iron-chelating tropolones anhydrosepedonin ( 1 ) and antibiotic C ( 2 ) in the mold Aspergillus nidulans . Additionally, the biosynthesis of the related polyketide tripyrnidone ( 5 ) was induced, whose novel tricyclic scaffold we elucidated by NMR and HRESIMS data. The corresponding biosynthetic polyketide synthase-encoding gene cluster responsible for the production of these compounds was identified. The tropolones as well as tripyrnidone ( 5 ) are produced by genes that belong to the broad reservoir of the fungal genome for the synthesis of different secondary metabolites, which are usually silenced under standard laboratory conditions. These molecules might be part of the bacterium-fungus competition in the complex soil environment, with the bacterial glycopeptide antibiotic as specific environmental trigger for fungal induction of this cluster., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gerke, Köhler, Wennrich, Große, Shao, Heinrich, Bode, Chen, Surup and Braus.)

Axenic fermentation on solid rice of the saprobic fungus Sparticola junci afforded two new highly oxidized naphthalenoid polyketide derivatives, sparticatechol A ( 1 ) and sparticolin H ( 2 ) along with sparticolin A ( 3 ). The structures of 1 and 2 were elucidated on the basis of their NMR and HR-ESIMS spectroscopic data. Assignment of absolute configurations was performed using electronic circular dichroism (ECD) experiments and Time-Dependent Density Functional Theory (TDDFT) calculations. Compounds 1-3 were evaluated for COX inhibitory, antiproliferative, cytotoxic and antimicrobial activities. Compounds 1 and 2 exhibited strong inhibitory activities against COX-1 and COX-2. Molecular docking analysis of 1 conferred favorable binding against COX-2. Sparticolin H ( 2 ) and A ( 3 ) showed a moderate antiproliferative effect against myelogenous leukemia K-562 cells and weak cytotoxicity against HeLa and mouse fibroblast cells.

Strain M2 T was isolated from the beach of Cuxhaven, Wadden Sea, Germany, in course of a program to attain new producers of bioactive natural products. Strain M2 T produces litoralimycin and sulfomycin-type thiopeptides. Bioinformatic analysis revealed a potential biosynthetic gene cluster encoding for the M2 T thiopeptides. The strain is Gram-stain-positive, rod shaped, non-motile, spore forming, showing a yellow colony color and forms extensively branched substrate mycelium and aerial hyphae. Inferred from the 16S rRNA gene phylogeny strain M2 T affiliates with the genus Streptomonospora. It shows 96.6% 16S rRNA gene sequence similarity to the type species Streptomonospora salina DSM 44593  T and forms a distinct branch with Streptomonospora sediminis DSM 45723  T with 97.0% 16S rRNA gene sequence similarity. Genome-based phylogenetic analysis revealed that M2 T is closely related to Streptomonospora alba YIM 90003  T with a digital DNA-DNA hybridisation (dDDH) value of 26.6%. The predominant menaquinones of M2 T are MK-10(H 6 ), MK-10(H 8 ), and MK-11(H 6 ) (> 10%). Major cellular fatty acids are iso-C 16:0, anteiso C 17:0 and C 18:0 10-methyl. The polar lipid profile consisted of diphosphatidylglycerol phosphatidyl glycerol, phosphatidylinositol, phosphatidylcholine, phosphatidylethanolamine, three glycolipids, two unknown phospholipids, and two unknown lipids. The genome size of type strain M2 T is 5,878,427 bp with 72.1 mol % G + C content. Based on the results obtained from phylogenetic and chemotaxonomic studies, strain M2 T (= DSM 106425  T  = NCCB 100650  T ) is considered to represent a novel species within the genus Streptomonospora for which the name Streptomonospora litoralis sp. nov. is proposed., (© 2021. The Author(s).)

Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.

A recent find of a Marasmius species in Northern Thailand led to the isolation of five unprecedented derivatives of the carotane antibiotic fulvoferruginin ( 1 ), fulvoferruginins B-F ( 2 - 6 ). The structures of these sesquiterpenoids were elucidated using HRESIMS, 1D and 2D NMR, as well as CD spectroscopy. Assessing the bioactivity, fulvoferruginin emerged as a potent cytotoxic agent of potential pharmaceutical interest., (Copyright © 2021, Sandargo et al.)

The new genus Morinagamyces is introduced herein to accommodate the fungus Apiosordaria vermicularis as inferred from a phylogenetic study based on sequences of the internal transcribed spacer region (ITS), the nuclear rDNA large subunit (LSU), and partial fragments of ribosomal polymerase II subunit 2 ( rpb 2) and β-tubulin ( tub 2) genes. Morinagamyces vermicularis was analyzed for the production of secondary metabolites, resulting in the isolation of a new depsipeptide named morinagadepsin ( 1 ), and the already known chaetone B ( 3 ). While the planar structure of 1 was elucidated by extensive 1D- and 2D-NMR analysis and high-resolution mass spectrometry, the absolute configuration of the building blocks Ala, Val, and Leu was determined as -l by Marfey's method. The configuration of the 3-hydroxy-2-methyldecanyl unit was assigned as 22 R ,23 R by J -based configuration analysis and Mosher's method after partial hydrolysis of the morinagadepsin to the linear derivative compound 2 . Compound 1 showed cytotoxic activity against the mammalian cell lines KB3.1 and L929, but no antimicrobial activity against the fungi and bacteria tested was observed, while 2 was inactive. Compound 3 was weakly cytotoxic against the cell line L929, but did not show any antimicrobial activity.

Submerged mycelial cultures of the ascomycete Colpoma   quercinum CCTU A372 were found to produce five previously undescribed tetramic acids, for which we propose the trivial names colposetins A-C ( 1 - 3 ) and colpomenoic acids A and B ( 4 and 5 ), along with the known compounds penicillide ( 6 ) and monodictyphenone ( 7 ). The planar structures of 1 - 5 were determined by high-resolution electrospray ionization mass spectrometry (HR-ESIMS) and extensive 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. Their absolute configurations were determined by the combination of electronic circular dischroism (ECD) analysis, J -based configurational analysis, and a rotating-frame Overhauser effect spectroscopy (ROESY) experiment. Colposetin B displayed weak antimicrobial activity against Bacillus subtilis and Mucor hiemalis (MIC 67 µg/mL).

The rare actinobacterium Amycolatopsis sp. strain 195334CR was found to produce previously undescribed cyclic hexapeptides, which we named amycolatomycin A and B ( 1 and 2 ). Their planar structures were determined by high-resolution mass spectrometry as well as extensive 1D and 2D NMR spectroscopy, while the absolute stereochemistry of its amino acids were determined by Marfey's method. Moreover, 1 and 2 differ by the incorporation of l-Ile and l- allo -Ile, respectively, whose FDVA (Nα-(2,4-Dinitro-5-fluorphenyl)-L-valinamide) derivatives were separated on a C 4 column. Their hallmark in common is a unique 2,6-dichloro-tryptophan amino acid unit. Amycolatomycin A ( 1 ) exhibited weak activity against Bacillus subtilis DSM 10 (minimum inhibitory concentration (MIC) = 33.4 µg/mL).

Triangularia mangenotti was analyzed for the production of secondary metabolites, resulting in the isolation of known zopfinol ( 1 ) and its new derivatives zopfinol B-C ( 2-4 ), the 10-membered lactones 7-O-acetylmultiplolide A ( 5 ) and 8-O-acetylmultiplolide A ( 6 ), together with sordarin ( 7 ), sordarin B ( 8 ), and hypoxysordarin ( 9 ). The absolute configuration of 1 was elucidated by the synthesis of MPTA-esters. Compound 1 showed antimicrobial activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus and the fungus Mucor hiemalis . While 4 was weakly antibacterial, 3 showed stronger antibiotic activity against the Gram-positive bacteria and weak antifungal activity against M. hiemalis and Rhodotorula glutinis . We furthermore observed the cytotoxicity of 1 , 3 and 4 against the mammalian cell lines KB3.1 and L929. Moreover, the new genus Pseudorhypophila is introduced herein to accommodate Triangularia mangenotii together with several species of Zopfiella - Z. marina , Z. pilifera , and Z. submersa . These taxa formed a well-supported monophyletic clade in the recently introduced family Navicularisporaceae, located far from the type species of the respective original genera, in a phylogram based on the combined dataset sequences of the internal transcribed spacer region (ITS), the nuclear rDNA large subunit (LSU), and fragments of the ribosomal polymerase II subunit 2 ( rpb2 ) and β-tubulin ( tub2 ) genes. Zopfiella submersa is synonymized with P. marina due to the phylogenetic and morphological similarity. The isolation of zopfinols 1 - 4 and sordarins 7 - 9 confirms the potential of this fungal order as producers of bioactive compounds and suggests these compounds as potential chemotaxonomic markers.

Hypoxylon, a large, cosmopolitan genus of Ascomycota is in the focus of our current poly-thetic taxonomic studies, and served as an excellent source for bioactive secondary metabolites at the same time. The present work concerns a survey of the Hypoxylon fuscum species complex based on specimens from Iran and Europe by morphological studies and high performance liquid chromatography coupled to mass spectrometry and diode array detection (HPLC-MS-DAD). Apart from known chemotaxonomic markers like binaphthalene tetrol (BNT) and daldinin F, two unprece-dented molecules were detected and subsequently isolated to purity by semi preparative HPLC. Their structures were established by nuclear-magnetic resonance (NMR) spectroscopy as 3'-malonyl-daldinin F ( 6 ) and pseudofuscochalasin A ( 4 ). The new daldinin derivative 6 showed weak cytotoxicity towards mammalian cells but bactericidal activity. The new cytochalasin 4 was compared to cytochalasin C in an actin disruption assay using fluorescence microscopy of human osteo-sarcoma U2OS cells, revealing comparable activity towards F-actin but being irreversible compared to cytochalasin C. Concurrently, a multilocus molecular phylogeny based on ribosomal and proteinogenic nucleotide sequences of Hypoxylon species resulted in a well-supported clade for H. fuscum and its allies. From a comparison of morphological, chemotaxonomic and phylogenetic evidence, we introduce the new species H. eurasiaticum and H. pseudofuscum .

The diversity of azaphilones in stromatal extracts of the fungus Hypoxylon fragiforme was investigated and linked to their biosynthetic machineries by using bioinformatics. Nineteen azaphilone-type compounds were isolated and characterized by NMR spectroscopy and mass spectrometry, and their absolute stereoconfigurations were assigned by using Mosher ester analysis and electronic circular dichroism spectroscopy. Four unprecedented bis-azaphilones, named hybridorubrins A-D, were elucidated, in addition to new fragirubrins F and G and various known mitorubrin derivatives. Only the hybridorubrins, which are composed of mitorubrin and fragirubrin moieties, exhibited strong inhibition of Staphylococcus aureus biofilm formation. Analysis of the genome of H. fragiforme revealed the presence of two separate biosynthetic gene clusters (BGCs) hfaza1 and hfaza2 responsible for azaphilone formation. While the hfaza1 BGC likely encodes the assembly of the backbone and addition of fatty acid moieties to yield the (R)-configured series of fragirubrins, the hfaza2 BGC contains the necessary genes to synthesise the widely distributed (S)-mitorubrins. This study is the first example of two distant cross-acting fungal BGCs collaborating to produce two families of azaphilones and bis-azaphilones derived therefrom., (© 2020 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Extracts of Opuntia stricta var. dillenii fruits were fractionated by semi-preparative high-performance countercurrent chromatography (HPCCC) to study the secondary metabolite formation, whereby HPCCC showed a superior separation capacity to fractionate minor metabolites compared to HPLC. A family of new peptides was detected in semi-polar fractions when monitoring the HPCCC separation by off-line injections of fractions to ESI-MS/MS. Planar structures of the major compounds, two 14-ring-membered cyclopeptide alkaloids, which were named opuntisines A and B, were elucidated by 1D- and 2D-NMR spectroscopy and HR-ESI-MS/MS spectrometry, while a combination of chemical derivatisation and degradation revealed the stereo-configurations. Specifically, the methods of Marfey and Mosher indicated l-Glu, l-Ile, l-Phe and 1S-configurations, respectively; ROESY correlations revealed 8S, 9S. The novel opuntisine A showed moderate activity against the Gram-negative bacterium Escherichia coli, but no further antibacterial, antifungal nor cytotoxic effects. This bioactive natural product class is reported for the first time in the plant family Cactaceae., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Species belonging to the bacterial phylum Planctomycetes are ubiquitous members of the microbial communities in aquatic environments and are frequently isolated from various biotic and abiotic surfaces in marine and limnic water bodies. Planctomycetes have large genomes of up to 12.4 Mb, follow complex lifestyles and display an uncommon cell biology; features which motivate the investigation of members of this phylum in greater detail. As a contribution to the current collection of axenic cultures of Planctomycetes, we here describe strain Pla52 T isolated from wood particles in the Baltic Sea. Phylogenetic analysis places the strain in the family Pirellulaceae and suggests two species of the recently described genus Stieleria as current closest neighbours. Strain Pla52n T shows typical features of members of the class Planctomycetia, including division by polar budding and the presence of crateriform structures. Colonies of strain Pla52n T have a light orange colour, which is an unusual pigmentation compared to the majority of members in the phylum, which show either a pink to red pigmentation or entirely lack pigmentation. Optimal growth of strain Pla52n T at 33 °C and pH 7.5 indicates a mesophilic (i.e. with optimal growth between 20 and 45 °C) and neutrophilic growth profile. The strain is an aerobic heterotroph with motile daughter cells. Its genome has a size of 9.6 Mb and a G + C content of 56.0%. Polyphasic analyses justify delineation of the strain from described species within the genus Stieleria. Therefore, we conclude that strain Pla52n T = LMG 29463 T = VKM B-3447 T  should be classified as the type strain of a novel species, for which we propose the name Stieleria varia sp. nov.

Two new tetracyclic polyketides with a spirocenter, simplicilones A ( 1 ) and B ( 2 ) were isolated from the broth-culture of the endophytic fungus Simplicillium subtropicum (SPC3) in the course of our screening for new bioactive secondary metabolites. This endophytoic fungus is naturally harboured in the fresh bark of the Cameroonian medicinal plant Duguetia staudtii (Engl. and Diels) Chatrou. The planar structures of the simplicilones were elucidated by MS and 1D as well as 2D NMR spectroscopic techniques. The relative configuration was assigned by NOESY experiments in conjunction with coupling constants; subsequently, the absolute configurations were assigned by the modified Mosher's method. The compounds showed weak cytotoxic effects against the cell line KB3.1 (in vitro cytotoxicity (IC 50 ) = 25 µg/mL for 1 , 29 µg/mL for 2 ), but were inactive against the tested Gram-positive and Gram-negative bacteria as well as fungi.

Investigation of the metabolome of the ascomycete Annulohypoxylon truncatum led to the identification of novel oxygenated brasilane glycosides and the revision of the stereochemistry of the brasilane A octahydro-1H-indene core scaffold to trans. The bra biosynthetic gene cluster containing five genes (braA-braE) was identified and verified by heterologous expression experiments in Aspergillus oryzae demonstrating that BraC is a multifunctional P450 monooxygenase. In vitro studies of BraB revealed it to be a very rare fungal UDP-GlcNAc dependent N-acetylglucosamine transferase. UDP-glucose is also accepted as a donor, and a broad acceptor substrate tolerance for various primary and secondary alcohols was observed.

During the course of a screening for novel biologically active secondary metabolites produced by the Sordariomycetes (Ascomycota, Fungi), the ex-type strain of Jugulospora vestita was found to produce seven novel xanthone-anthraquinone heterodimers, xanthoquinodin A11 ( 1 ) and xanthoquinodins B10-15 ( 2 - 7 ), together with the already known compound xanthoquinodin B4 ( 8 ). The structures of the xanthoquinodins were determined by analysis of the nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric data. Moreover, the absolute configurations of these metabolites were established by analysis of the 1 H- 1 H coupling constants, nuclear Overhauser effect spectroscopy (NOESY) correlations, and Electronic Circular Dichroism (ECD) spectroscopic data. Antifungal and antibacterial activities as well as cytotoxicity of all compounds were tested. Xanthoquinodin B11 showed fungicidal activities against Mucor hiemalis [minimum inhibitory concentration (MIC) 2.1 µg/mL], Rhodotorula glutinis (MIC 2.1 µg/mL), and Pichia anomala (MIC 8.3 µg/mL). All the compounds 1 - 8 displayed anti-Gram-positive bacteria activity (MIC 0.2-8.3 µg/mL). In addition, all these eight compounds showed cytotoxicity against KB 3.1, L929, A549, SK-OV-3, PC-3, A431, and MCF-7 mammalian cell lines. The six novel compounds ( 1 - 3 , 5 - 7 ), together with xanthoquinodin B4, were also found in the screening of other strains belonging to Jugulospora rotula , revealing the potential chemotaxonomic significance of the compound class for the genus.

Symbiotic microbes help a myriad of insects acquire nutrients. Recent work suggests that insects also frequently associate with actinobacterial symbionts that produce molecules to help defend against parasites and predators. Here we explore a potential association between Actinobacteria and two species of fungus-farming ambrosia beetles, Xyleborinus saxesenii and Xyleborus affinis . We isolated and identified actinobacterial and fungal symbionts from laboratory reared nests, and characterized small molecules produced by the putative actinobacterial symbionts. One 16S rRNA phylotype of Streptomyces (XylebKG-1) was abundantly and consistently isolated from the galleries and adults of X. saxesenii and X. affinis nests. In addition to Raffaelea sulphurea , the symbiont that X. saxesenii cultivates, we also repeatedly isolated a strain of Nectria sp. that is an antagonist of this mutualism. Inhibition bioassays between Streptomyces griseus XylebKG-1 and the fungal symbionts from X. saxesenii revealed strong inhibitory activity of the actinobacterium toward the fungal antagonist Nectria sp. but not the fungal mutualist R. sulphurea. Bioassay guided HPLC fractionation of S. griseus XylebKG-1 culture extracts, followed by NMR and mass spectrometry, identified cycloheximide as the compound responsible for the observed growth inhibition. A biosynthetic gene cluster putatively encoding cycloheximide was also identified in S. griseus XylebKG-1. The consistent isolation of a single 16S phylotype of Streptomyces from two species of ambrosia beetles, and our finding that a representative isolate of this phylotype produces cycloheximide, which inhibits a parasite of the system but not the cultivated fungus, suggests that these actinobacteria may play defensive roles within these systems., (Copyright © 2020 Grubbs, Surup, Biedermann, McDonald, Klassen, Carlson, Clardy and Currie.)

Bacteria of the phylum Planctomycetes occur ubiquitously in marine environments and play important roles in the marine nitrogen- and carbon cycle, for example as scavengers after phototrophic blooms. Here, we describe the isolation and characterization of the planctomycetal strain Enr13 T isolated from a Posidonia sp. biofilm obtained from seawater sediment close to Panarea Island, Italy. Phylogenetic tree reconstruction based on 16S rRNA gene sequences and multi-locus sequence analysis supports the delineation of strain Enr13 T from characterized species part of the phylum of Planctomycetes . HPLC-MS analysis of culture broth obtained from strain Enr13 T revealed the presence of lipophilic metabolites, of which the major compound was isolated by preparative reversed-phase HPLC. The structure of this compound, named stieleriacine D ( 1 ), was elucidated utilizing HRESIMS, 1D- and 2D-NMR data as a new N -acylated dehydrotyrosine derivative. Its biosynthesis was proposed based on an in silico gene cluster analysis. Through analysis of the MS/MS spectrum of 1 and its minor derivative, stieleriacine E ( 2 ), it was possible to assign the structure of 2 without isolation. 1 showed antibacterial activity, however, the wide distribution of structurally related compounds indicates a potential role as a signaling molecule., (Copyright © 2020 Sandargo, Jeske, Boedeker, Wiegand, Wennrich, Kallscheuer, Jogler, Rohde, Jogler and Surup.)

Bacterial strains of the phylum Planctomycetes occur ubiquitously, but are often found on surfaces of aquatic phototrophs, e.g. alga. Despite slower growth, planctomycetes are not outcompeted by faster-growing bacteria in biofilms on such surfaces; however, strategies allowing them to compensate for slower growth have not yet been investigated. Here, we identified stieleriacines, a class of N-acylated tyrosines produced by the novel planctomycete Stieleria maiorica Mal15 T , and analysed their effects on growth of the producing strain and bacterial species likely co-occurring with strain Mal15 T . Stieleriacines reduced the lag phase of Mal15 T and either stimulated or inhibited biofilm formation of two bacterial competitors, indicating that Mal15 T employs stieleriacines to specifically alter microbial biofilm composition. The genetic organisation of the putative stieleriacine biosynthetic cluster in strain Mal15 T points towards a functional link of stieleriacine biosynthesis to exopolysaccharide-associated protein sorting and biofilm formation.

Streptomonospora sp. M2 has been isolated from a soil sample collected at the Wadden Sea beach in our ongoing program aimed at the isolation of rare Actinobacteria, ultimately targeting the discovery of new antibiotics. Because crude extracts derived from cultures of this strain showed inhibitory activity against the indicator organism Bacillus subtilis , it was selected for further analysis. HPLC-MS analysis of its culture broth revealed the presence of lipophilic metabolites. The two major metabolites of those were isolated by preparative reversed-phase HPLC and preparative TLC. Their planar structures were elucidated using high-resolution electrospray ionization mass spectrometry (HRESIMS), 1D and 2D NMR data as new thiopeptide antibiotics and named litoralimycin A ( 1 ) and B ( 2 ). Although rotating frame nuclear Overhauser effect spectroscopy (ROESY) data established a Z configuration of the Δ 21 ,2 6 double bond, the stereochemistry of C-5 and C-15 were assigned as S by Marfey's method after ozonolysis. The biological activity spectrum of 1 and 2 is highly uncommon for thiopeptide antibiotics, since they showed only insignificant antibacterial activity, but 1 showed strong cytotoxic effects., Competing Interests: The authors declare no conflict of interest.

During a survey of xylarialean fungi in Northern Iran, several specimens that showed affinities to the Hypoxylon rubiginosum complex were collected and cultured. A comparison of their morphological characters, combined with a chemotaxonomic study based on high performance liquid chromatography, coupled with diode array detection and mass spectrometry (HPLC-DAD/MS) and a multi-locus phylogeny based on ITS, LSU, rbp2 and tub2 DNA sequences, revealed a new species here described as Hypoxylon guilanense . In addition, Hypoxylon rubiginosum sensu stricto was also encountered. Concurrently, an endophytic isolate of the latter species showed strong antagonistic activities against the Ash Dieback pathogen, Hymenoscyphus fraxineus , in a dual culture assay in our laboratory. Therefore, we decided to test the new Iranian fungi for antagonistic activities against the pathogen, along with several cultures of other Hypoxylon species that are related to H. rubiginosum . Our results suggest that the antagonistic effects of Hypoxylon spp. against Hym. fraxineus are widespread and that they are due to the production of antifungal phomopsidin derivatives in the presence of the pathogen., (Mohammad Javad Pormoghadam, Christopher Lambert, Frank Surup, Seyed Akbar Khodaparast, Irmgard Krisai-Greilhuber, Hermann Voglmayr, Marc Stadler.)

Seven previously unknown sesquiterpenoids and norsesquiterpenoids, rhodocoranes F-L ( 1 - 7 ), were isolated from the fermentation broth of the basidiomycete Rhodotus palmatus . Their structures were elucidated utilizing 1D and 2D NMR techniques as well as HRESIMS; they are unusual noracorane, spiro[4.4]nonene, and acorane-type sesquiterpenoids. They include the first naturally occurring cyclopentylidenefuranones ( 3 - 5 ) and the new tricyclic scaffold of 7 . Metabolites 1 - 7 exhibited a general mild antimycotic activity, while 1 - 3 also displayed cytotoxic effects.

Rhodatin (1), a meroterpenoid featuring a unique pentacyclic scaffold with both spiro and spiroketal centers, and five unusual acorane-type sesquiterpenoids, named rhodocoranes A-E (2-6, respectively), are the first natural products isolated from the basidiomycete Rhodotus palmatus. Their structures were elucidated by two-dimensional NMR experiments and HRESIMS, while the absolute configuration of the substance family was determined by Mosher's method utilizing 2. Rhodatin strongly inhibited hepatitis C virus, whereas 4 displayed cytotoxicity and selective antifungal activity.

The strophariaceous basidiomycete Cyclocybe aegerita (synonyms Agrocybe aegerita and A. cylindracea ) is one of the most praised cultivated edible mushrooms and is being cultivated at large scale for food production. Furthermore, the fungus serves as a model organism to study fruiting body formation and the production of secondary metabolites during the life cycle of Basidiomycota. By studying the secondary metabolite profiles of C. aegerita , we found several terpenoids in submerged cultures. Aside from the main metabolite, bovistol ( 1 ), two new bovistol derivatives B and C ( 2 , 3 ) and pasteurestin C as a new protoilludane ( 4 ) were isolated by preparative HPLC. Their structures were elucidated by mass spectrometry and NMR spectroscopy. The relative configurations of 2 - 4 were assigned by ROESY correlations, and 3 J H,H coupling constants in the case of 4 . Applying quantitative PCR for gene expression validation, we linked the production of bovistol and its derivatives to the respective biosynthesis gene clusters.

Chemical analysis of extracts from cultures of the plant pathogenic fungus Cytospora sp. strain CCTU A309 collected in Iran led to the isolation of two previously unreported heptanedioic acid derivatives namely (2R,3S) 2-hydroxy-3-phenyl-4-oxoheptanedioic acid (1) and (2S,3S) 2-hydroxy-3-phenyl-4-oxoheptanedioic acid (2) as diastereomers, four previously undescribed prenylated p-terphenyl quinones 3-6 in addition to five known metabolites. Their structures were elucidated on the basis of extensive spectroscopic analysis and high-resolution mass spectrometry. For metabolites 1 and 2, the absolute configurations at C-2 were deduced from comparison of the 1 H NMR difference of their (S)- and (R)-phenylglycine methyl ester derivatives while the relative configurations were tentatively assigned by a J-based analysis and confirmed by comparison of 13 C chemical shifts to literature data. The isolated compounds were tested for their cytotoxic, antimicrobial (including biofilm inhibition), antiviral, and nematicidal activities. While only moderate antimicrobial effects were observed, the terphenyl quinone derivatives 3-6 and leucomelone (10) exhibited significant cytotoxicity against the mouse fibroblast L929 and cervix carcinoma KB-3-1 cell lines with IC 50 values ranging from 2.4 to 26 μg/mL. Furthermore, metabolites 4-6 showed interesting antiviral activity against hepatitis C virus (HCV)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Natural products often contain interesting new chemical entities that are introduced into the structure of a compound by the enzymatic machinery of the producing organism. The recently described crocagins are novel polycyclic peptides which belong to the class of ribosomally synthesized and post-translationally modified peptide natural products. They have been shown to bind to the conserved prokaryotic carbon-storage regulator A in vitro. In efforts to understand crocagin biosynthesis, the putative biosynthetic genes were expressed and purified. Here, the first crystal structure of a protein from the crocagin-biosynthetic gene cluster, CgnJ, a domain of unknown function protein, is reported. Possible functions of this protein were explored by structural and sequence homology analyses. Even though the sequence homology to proteins in the Protein Data Bank is low, the protein shows significant structural homology to a protein with known function within the competency system of Bacillus subtilis, ComJ, leading to the hypothesis of a similar role of the protein within the producing organism.

In our ongoing search for new bioactive fungal metabolites, two new cytochalasans were isolated from stromata of the hypoxylaceous ascomycete Hypoxylon fragiforme . Their structures were elucidated via high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. Together with 23 additional cytochalasans isolated from ascomata and mycelial cultures of different Ascomycota, they were tested on their ability to disrupt the actin cytoskeleton of mammal cells in a preliminary structure⁻activity relationship study. Out of all structural features, the presence of hydroxyl group at the C7 and C18 residues, as well as their stereochemistry, were determined as important factors affecting the potential to disrupt the actin cytoskeleton. Moreover, reversibility of the actin disrupting effects was tested, revealing no direct correlations between potency and reversibility in the tested compound group. Since the diverse bioactivity of cytochalasans is interesting for various applications in eukaryotes, the exact effect on eukaryotic cells will need to be determined, e.g., by follow-up studies involving medicinal chemistry and by inclusion of additional natural cytochalasans. The results are also discussed in relation to previous studies in the literature, including a recent report on the anti-Biofilm activities of essentially the same panel of compounds against the pathogenic bacterium, Staphylococcus aureus .

During the course of our ongoing work to discover new inhibitors of biofilm formation of Staphylococcus aureus from fungal sources, we observed biofilm inhibition by cytochalasans isolated from cultures of the ascomycete Hypoxylon fragiforme for the first time. Two new compounds were purified by a bioassay-guided fractionation procedure; their structures were elucidated subsequently by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). This unexpected finding prompted us to test further cytochalasans from other fungi and from commercial sources for comparison. Out of 21 cytochalasans, 13 showed significant inhibition of Staphylococcus aureus biofilm formation at subtoxic levels. These findings indicate the potential of cytochalasans as biofilm inhibitors for the first time, also because the minimum inhibitory concentrations (MIC) are independent of the anti-biofilm activities. However, cytochalasans are known to be inhibitors of actin, making some of them very toxic for eukaryotic cells. Since the chemical structures of the tested compounds were rather diverse, the inclusion of additional derivatives, as well as the evaluation of their selectivity against mammalian cells vs. the bacterium, will be necessary as next step in order to develop structure-activity relationships and identify the optimal candidates for development of an anti-biofilm agent., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

A Natural Compound Library containing myxobacterial secondary metabolites was screened in murine macrophages for novel activators of IL-1β maturation and secretion. The most potent of three hits in total was a so far undescribed metabolite, which was identified from the myxobacterium Hyalangium minutum strain Hym3. While the planar structure of 1 was elucidated by high resolution mass spectrometry and NMR data yielding an asymmetric boron containing a macrodiolide core structure, its relative stereochemistry of all 20 stereocenters of the 42-membered ring was assigned by rotating frame Overhause effect spectroscopy correlations, 1 H, 1 H, and 1 H, 13 C coupling constants, and by comparison of 13 C chemical shifts to those of the structurally related metabolites tartrolon B-D. The absolute stereochemistry was subsequently assigned by Mosher's and Marfey's methods. Further functional studies revealed that hyaboron and other boronated natural compounds resulted in NLRP3 inflammasome dependent IL-1β maturation, which is most likely due to their ability to act as potassium ionophores. Moreover, besides its inflammasome-stimulatory activity in human and mouse cells, hyaboron (1) showed additional diverse biological activities, including antibacterial and antiparasitic effects.

4-Hydroxypleurogrisein, a congener of the anticancer-lead compound pleurotin, as well as six further derivatives were isolated from the basidiomycete Hohenbuehelia grisea , strain MFLUCC 12-0451. The structures were elucidated utilizing high resolution electron spray ionization mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR) spectral data and evaluated for their biological activities; for leucopleurotin, we provide Xray data. While most congeners showed moderate antimicrobial and cytotoxic activity, 4-hydroxypleurogrisein emerged as an inhibitor of hepatitis C virus infectivity in mammalian liver cells.