ABSTRACT
The endophytic fungus Chaetomium nigricolor culture filtrate's hexane extract was used to identify a cytotoxic very long-chain fatty acid. Based on multiple spectroscopic investigations, the structure of the compound was predicted to be an unsaturated fatty acid, Nonacosenoic acid (NA). Using the MTT assay, the compound's cytotoxic potential was evaluated against MCF-7, A-431, U-251, and HEK-293 T cells. The compound was moderately cytotoxic to breast carcinoma cell line, MCF-7 cells and negligibly cytotoxic to non-cancerous cell line HEK-293 T cells. The compound exhibited mild cytotoxic activity against A-431 and U-251 cells. The compound also induced ROS generation and mitochondrial depolarization in MCF-7 cells when assessed via the NBT and JC-1 assays, respectively. This is the first report on the production of nonacosenoic acid from the endophytic fungus Chaetomium nigricolor and the assessment of its bioactivity.
Subject(s)
Chaetomium , Endophytes , Fatty Acids, Unsaturated , Chaetomium/chemistry , Humans , Endophytes/chemistry , Endophytes/metabolism , Endophytes/isolation & purification , Fatty Acids, Unsaturated/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Plant Stems/microbiology , Plant Stems/chemistry , Cell Survival/drug effects , Reactive Oxygen Species/metabolism , Cell LineABSTRACT
Chetocochliodin M (5) containing a rare cage-ring and chetocochliodin N (6) featuring an unusual piperazine-2,3-dione ring system together with known analogues chetomin (1), chetoseminudin C (2), chetocochliodin I (3), and oidioperazine E (4) were targeted for purification from the fungus Chaetomium cochliodes using a UPLC-Q-TOF-MS/MS approach. The structures of the new compounds were elucidated using HR-ESI-MS, NMR, and ECD spectra. Compounds 1, 3, and 6 exhibited strong cytotoxic activities against A549 and HeLa cancer cell lines.
Subject(s)
Chaetomium , Tandem Mass Spectrometry , Chaetomium/chemistry , Humans , Molecular Structure , Tandem Mass Spectrometry/methods , HeLa Cells , Chromatography, High Pressure Liquid/methods , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Drug Screening Assays, Antitumor , A549 Cells , Piperazines/pharmacology , Piperazines/chemistry , Piperazines/isolation & purificationABSTRACT
Two new cytochalasans, marcytoglobosins A (1) and B (2) were isolated from the marine sponge associated fungus Chaetomium globosum 162105, along with six known compounds (3-8). The complete structures of two new compounds were determined based on 1D/2D NMR and HR-MS spectroscopic analyses coupled with ECD calculations. All eight isolates were evaluated for their antibacterial activity. Among them, compounds 3-8 displayed antibacterial effects against Staphylococcus epidermidis, Bacillus thuringiensis, Pseudomonas syringae pv. Actinidiae, Vibrio alginolyticus, and Edwardsiella piscicida with minimum inhibitory concentration (MIC) values ranging from 10 to 25â µg/mL.
Subject(s)
Anti-Bacterial Agents , Chaetomium , Microbial Sensitivity Tests , Porifera , Chaetomium/chemistry , Animals , Porifera/microbiology , Porifera/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Cytochalasins/pharmacology , Cytochalasins/chemistry , Cytochalasins/isolation & purification , Molecular ConformationABSTRACT
Two new sesterterpenoids, sesterchaetins A and B (1 and 2), and two new diepoxide polyketides, chaetoketoics A and B (3 and 4), were characterized from the culture extract of Chaetomium globosum SD-347, a fungal strain derived from deep sea-sediment. Their structures and absolute configurations were unambiguously determined by detailed NMR, mass spectra, and X-ray crystallographic analysis. Compounds 1 and 2 contained a distinctive 5/8/6/5 tetracyclic carbon-ring-system, which represented a rarely occurring natural product framework. The new isolates 1-4 exhibited selective antimicrobial activities against human and aquatic pathogenic bacteria and plant-pathogenic fungi.
Subject(s)
Anti-Infective Agents , Chaetomium , Polyketides , Sesquiterpenes , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Anti-Infective Agents/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology , Polyketides/chemistry , Polyketides/isolation & purification , Aquatic Organisms/chemistry , Chaetomium/chemistry , Bacteria/drug effects , Crystallography, X-RayABSTRACT
Using CRISPR-Cas9 technology and a microhomology-mediated end-joining repair system, we substituted genes of the gliotoxin pathway in Aspergillus fumigatus with genes responsible for chetomin biosynthesis from Chaetomium cochliodes, leading to the production of three new epipolythiodioxopiperazines (ETPs). This work represents the first successful endeavor to produce ETPs in a non-native host. Additionally, the simultaneous disruption of five genes in a single transformation marks the most extensive gene knockout event in filamentous fungi to date.
Subject(s)
Aspergillus fumigatus , Gliotoxin , Piperazines , Aspergillus fumigatus/metabolism , Aspergillus fumigatus/genetics , Piperazines/chemistry , Piperazines/metabolism , Gliotoxin/biosynthesis , Gliotoxin/chemistry , Molecular Structure , Chaetomium/metabolism , Chaetomium/chemistry , CRISPR-Cas SystemsABSTRACT
By co-culturing two endophytic fungi (Chaetomium virescens and Xylaria grammica) collected from the medicinal and edible plant Smilax glabra Roxb. and analyzing them with MolNetEnhancer module on GNPS platform, seven undescribed chromone-derived polyketides (chaetoxylariones A-G), including three pairs of enantiomer ones (2a/2b, 4a/4b and 6a/6b) and four optical pure ones (1, 3, 5 and 7), as well as five known structural analogues (8-12), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray diffraction, 13C NMR calculation and DP4+ probability analyses, as well as the comparison of the experimental electronic circular dichroism (ECD) data. Structurally, compound 1 featured an unprecedented chromone-derived sulfonamide tailored by two isoleucine-derived δ-hydroxy-3-methylpentenoic acids via the acylamide and NO bonds, respectively; compound 2 represented the first example of enantiomeric chromone derivative bearing a unique spiro-[3.3]alkane ring system; compound 3 featured a decane alkyl side chain that formed an undescribed five-membered lactone ring between C-7' and C-10'; compound 4 contained an unexpected highly oxidized five-membered carbocyclic system featuring rare adjacent keto groups; compound 7 featured a rare methylsulfonyl moiety. In addition, compound 10 showed a significant inhibition towards SW620/AD300 cells with an IC50 value of PTX significantly decreased from 4.09 µM to 120 nM, and a further study uncovered that compound 10 could obviously reverse the MDR of SW620/AD300 cells.
Subject(s)
Antineoplastic Agents , Chaetomium , Chromones , Drug Screening Assays, Antitumor , Polyketides , Xylariales , Chromones/chemistry , Chromones/pharmacology , Chromones/isolation & purification , Polyketides/chemistry , Polyketides/pharmacology , Polyketides/isolation & purification , Molecular Structure , Xylariales/chemistry , Chaetomium/chemistry , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Structure-Activity Relationship , Dose-Response Relationship, Drug , Cell Line, Tumor , Coculture Techniques , Cell Proliferation/drug effectsABSTRACT
Seven new polyketides including three chromone derivatives (1-3) and four linear ones incorporating a tetrahydrofuran ring (4-7), along with three known compounds (8-10), were obtained from the fermentation of an endophytic fungus (Chaetomium sp. UJN-EF006) isolated from the leaves of Vaccinium bracteatum. The structures of these fungal metabolites have been elucidated by spectroscopic means including MS, NMR and electronic circular dichroism. A preliminary anti-inflammatory screening with the lipopolysaccharide (LPS) induced RAW264.7â cell model revealed moderate NO production inhibitory activity for compounds 1 and 4. In addition, the expression of three LPS-induced inflammatory factors IL-6, iNOS and COX-2 was also blocked by 1 and 4.
Subject(s)
Chaetomium , Polyketides , Vaccinium myrtillus , Chaetomium/chemistry , Polyketides/chemistry , Lipopolysaccharides/pharmacology , Molecular StructureABSTRACT
The antimicrobial resistance of pathogenic microorganisms against commercial drugs has become a major problem worldwide. This study is the first of its kind to be carried out in Egypt to produce antimicrobial pharmaceuticals from isolated native taxa of the fungal Chaetomium, followed by a chemical investigation of the existing bioactive metabolites. Here, of the 155 clinical specimens in total, 100 pathogenic microbial isolates were found to be multi-drug resistant (MDR) bacteria. The Chaetomium isolates were recovered from different soil samples, and wild host plants collected from Egypt showed strong inhibitory activity against MDR isolates. Chaetomium isolates displayed broad-spectrum antimicrobial activity against C. albicans, Gram-positive, and Gram-negative bacteria, with inhibition zones of 11.3 to 25.6 mm, 10.4 to 26.0 mm, and 10.5 to 26.5 mm, respectively. As a consecutive result, the minimum inhibitory concentration (MIC) values of Chaetomium isolates ranged from 3.9 to 62.5 µg/mL. Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) analysis was performed for selected Chaetomium isolates with the most promising antimicrobial potential against MDR bacteria. The LC-MS/MS analysis of Chaetomium species isolated from cultivated soil at Assuit Governate, Upper Egypt (3), and the host plant Zygophyllum album grown in Wadi El-Arbaein, Saint Katherine, South Sinai (5), revealed the presence of alkaloids as the predominant bioactive metabolites. Most detected bioactive metabolites previously displayed antimicrobial activity, confirming the antibacterial potential of selected isolates. Therefore, the Chaetomium isolates recovered from harsh habitats in Egypt are rich sources of antimicrobial metabolites, which will be a possible solution to the multi-drug resistant bacteria tragedy.
Subject(s)
Anti-Infective Agents , Chaetomium , Chaetomium/chemistry , Chromatography, Liquid , Tandem Mass Spectrometry , Anti-Infective Agents/metabolism , Anti-Bacterial Agents/chemistry , Bacteria/metabolism , Microbial Sensitivity Tests , SoilABSTRACT
Loss of H2A-H2B histone dimers is a hallmark of actively transcribed genes, but how the cellular machinery functions in the context of noncanonical nucleosomal particles remains largely elusive. In this work, we report the structural mechanism for adenosine 5'-triphosphate-dependent chromatin remodeling of hexasomes by the INO80 complex. We show how INO80 recognizes noncanonical DNA and histone features of hexasomes that emerge from the loss of H2A-H2B. A large structural rearrangement switches the catalytic core of INO80 into a distinct, spin-rotated mode of remodeling while its nuclear actin module remains tethered to long stretches of unwrapped linker DNA. Direct sensing of an exposed H3-H4 histone interface activates INO80, independently of the H2A-H2B acidic patch. Our findings reveal how the loss of H2A-H2B grants remodelers access to a different, yet unexplored layer of energy-driven chromatin regulation.
Subject(s)
Chaetomium , Chromatin Assembly and Disassembly , Chromatin , Histones , Nucleosomes , Chromatin/chemistry , DNA/chemistry , Histones/chemistry , Nucleosomes/chemistry , Cryoelectron Microscopy , Chaetomium/chemistry , Chaetomium/ultrastructureABSTRACT
Punctaporonins T (1) and U (2), new caryophyllene sesquiterpenes, were isolated with three known punctaporonins, A (3), B (4), and C (5), from the endophytic fungus Chaetomium globosum (TC2-041). The structures and relative configurations of punctaporonins T and U were elucidated based on a combination of HRESIMS, 1D/2D NMR spectroscopic analysis, and X-ray diffraction analysis, while their absolute configuration is presumed to be consistent with the co-isolated 3-5 on biogenetic arguments. Compound 1 showed weak inhibitory activity against both Mycobacterium tuberculosis and Staphylococcus aureus.
Subject(s)
Chaetomium , Plants, Medicinal , Sesquiterpenes , Endophytes/chemistry , Canada , Chaetomium/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Molecular StructureABSTRACT
The DEAH-box helicase Prp43 has essential functions in pre-mRNA splicing and ribosome biogenesis, remodeling structured RNAs. To initiate unwinding, Prp43 must first accommodate a single-stranded RNA segment into its RNA binding channel. This allows translocation of the helicase on the RNA. G-patch (gp) factors activate Prp43 in its cellular context enhancing the intrinsically low ATPase and RNA unwinding activity. It is unclear how the RNA loading process is accomplished by Prp43 and how it is regulated by its substrates, ATP and RNA, and the G-patch partners. We developed single-molecule (sm) FRET reporters on Prp43 from Chaetomium thermophilum to monitor the conformational dynamics of the RNA binding channel in Prp43 in real-time. We show that the channel can alternate between open and closed conformations. Binding of Pfa1(gp) and ATP shifts the distribution of states towards channel opening, facilitating the accommodation of RNA. After completion of the loading process, the channel remains firmly closed during successive cycles of ATP hydrolysis, ensuring stable interaction with the RNA and processive translocation. Without Pfa1(gp), it remains predominantly closed preventing efficient RNA loading. Our data reveal how the ligands of Prp43 regulate the structural dynamics of the RNA binding channel controlling the initial binding of RNA.
Subject(s)
Chaetomium , DEAD-box RNA Helicases , RNA , Adenosine Triphosphate/metabolism , Chaetomium/chemistry , Chaetomium/metabolism , DEAD-box RNA Helicases/metabolism , DNA Helicases/genetics , Molecular Conformation , RNA/metabolism , RNA Helicases/metabolism , RNA Splicing , Fluorescence Resonance Energy Transfer , Molecular Dynamics SimulationABSTRACT
Chaetomium (Chaetomiaceae), a large fungal genus consisting of at least 400 species, has been acknowledged as a promising resource for the exploration of novel compounds with potential bioactivities. Over the past decades, emerging chemical and biological investigations have suggested the structural diversity and extensive potent bioactivity of the specialized metabolites in the Chaetomium species. To date, over 500 compounds with diverse chemical types have been isolated and identified from this genus, including azaphilones, cytochalasans, pyrones, alkaloids, diketopiperazines, anthraquinones, polyketides, and steroids. Biological research has indicated that these compounds possess a broad range of bioactivities, including antitumor, anti-inflammatory, antimicrobial, antioxidant, enzyme inhibitory, phytotoxic, and plant growth inhibitory activities. This paper summarizes current knowledge referring to the chemical structure, biological activity, and pharmacologic potency of the specialized metabolites in the Chaetomium species from 2013 to 2022, which might provide insights for the exploration and utilization of bioactive compounds in this genus both in the scientific field and pharmaceutical industry.
Subject(s)
Alkaloids , Anti-Infective Agents , Chaetomium , Chaetomium/chemistry , Anti-Infective Agents/pharmacology , Alkaloids/chemistry , Diketopiperazines , Antioxidants/pharmacologyABSTRACT
Thirteen new alkaloids (1-13) as well as ten known compounds were isolated from the solid-state fermented rice medium of the fungus Chaetomium nigricolor YT-2. Their structures were elucidated on the basis of spectroscopic data, quantum calculations, and single crystal X-ray crystallographic analysis. Chaetonigrisin A (1) represents an unprecedented carbon skeleton featuring a polycyclic 1H-pyrano[3,2:3,4-]âfuro[2,â3-âb]âindole. Chaetonigrisin B (2) displays a unique carbon skeleton with a 1,3dioxolane bridged-ring. Chaetonigrisin C (3) is a spirocyclic indole alkaloid. Chaetonigrisins D-H (4-8) are a group of asymmetric dimers, formed with two 3-indol-3yl-1,2-propanediol (4-6) or with a 3-indol-3yl-1,2-propanediol and a 3-indol-2yl-1,2-propanediol (7-8) by a pyran ring. Chaetonigrisins I-L (9-12) each contains a 3-indol-3yl-1,2-propanediol or 3-indol-2yl-1,2-propanediol substructure. Chaetonigrisin M (13) is a new quinoline alkaloid. The neuroprotective activity assay showed that at the concentration of 40 µM, compounds (4-7, 11, and 12) improved the cell viability of PC12 cells were 49.26 %, 74.69 %, 74.76 %, 86.63 %, 66.89 %, and 69.92 %, respectively induced by 6-OHDA, compound 7 showed significant neuroprotective activity via upregulation of SOD1 mRNA and Bcl-2 mRNA.
Subject(s)
Alkaloids , Chaetomium , Chaetomium/chemistry , Propylene Glycol , Indole Alkaloids/chemistry , Alkaloids/chemistry , Carbon , RNA, Messenger , Molecular StructureABSTRACT
Five hydroxamate siderophores, chaetomadramines A-E (1-5), along with seven known compounds were isolated from the fermented rice culture of the fungus Chaetomium madrasense cib-1. Compounds 1-5 were structurally elucidated on the basis of spectroscopic data, which were a group of unusual hydroxamate siderophores, bearing a long fatty acyl on the α-NH2 of the Nδ-hydroxylated ornithine. Compounds 2-5 were new. The structural elucidation and spectroscopic data of 1 were reported for the first time. Compounds 2-4 significantly improved the survival rates of PC12 cells in the neuroprotective activity assay at the concentration of 40 µM.
Subject(s)
Chaetomium , Siderophores , Siderophores/chemistry , Molecular Structure , Chaetomium/chemistry , Hydroxamic AcidsABSTRACT
Filamentous marine fungi have proven to be a plentiful source of new natural products. Chaetomium, a widely distributed fungal genus in the marine environment, has gained much interest within the scientific community. In the last 20 years, many potential secondary metabolites have been detected from marine-derived Chaetomium. In this review, we attempt to provide a comprehensive summary of the natural products produced by marine-derived Chaetomium species. A total of 122 secondary metabolites that were described from 2001 to 2021 are covered. The structural diversity of the compounds, along with details of the sources and relevant biological properties are also provided, while the relationships between structures and their bioactivities are discussed. It is our expectation that this review will be of benefit to drug development and innovation.
Subject(s)
Biological Products , Chaetomium , Biological Products/chemistry , Chaetomium/chemistry , Chaetomium/metabolism , Drug DevelopmentABSTRACT
Ribosomes are complex and highly conserved ribonucleoprotein assemblies catalyzing protein biosynthesis in every organism. Here we present high-resolution cryo-EM structures of the 80S ribosome from a thermophilic fungus in two rotational states, which due to increased 80S stability provide a number of mechanistic details of eukaryotic translation. We identify a universally conserved 'nested base-triple knot' in the 26S rRNA at the polypeptide tunnel exit with a bulged-out nucleotide that likely serves as an adaptable element for nascent chain containment and handover. We visualize the structure and dynamics of the ribosome protective factor Stm1 upon ribosomal 40S head swiveling. We describe the structural impact of a unique and essential m1acp3 Ψ 18S rRNA hyper-modification embracing the anticodon wobble-position for eukaryotic tRNA and mRNA translocation. We complete the eEF2-GTPase switch cycle describing the GDP-bound post-hydrolysis state. Taken together, our data and their integration into the structural landscape of 80S ribosomes furthers our understanding of protein biogenesis.
Subject(s)
Chaetomium/metabolism , Cryoelectron Microscopy/methods , Peptide Elongation Factor 2/chemistry , Protein Biosynthesis , RNA, Ribosomal/chemistry , Ribosomes/chemistry , Ribosomes/metabolism , Chaetomium/chemistry , Peptide Elongation Factor 2/metabolism , RNA, Ribosomal/genetics , RNA, Ribosomal/metabolism , RNA, Transfer/metabolismABSTRACT
Chemical investigation on the deep-sea-derived fungus Chaetomium globosum led to the isolation of nine compounds. By extensive analyses of the 1D and 2D NMR as well as HR-ESI-MS spectra, their structures were elucidated as xylariol A (1), 1,3-dihydro-4,5,6-trihydroxy-7-methylisobenzofuran (2), epicoccone B (3), epicoccolide B (4), chaetoglobosin G (5), chaetoglobosin Fex (6), cochliodone A (7), cochliodone B (8), and chaetoviridin A (9), assorting as four phenolics (1-4), two cytochalosans (5-6), and three azaplilones (7-9). Compounds 1-3 were firstly reported from C.â globosum. Under the concentrations of 20 µg/mL, 1, 2, and 3 exhibited potent inâ vitro anti-HIV activity with the inhibition rates of 70 %, 75 %, and 88 %, respectively.
Subject(s)
Anti-HIV Agents/chemistry , Chaetomium/chemistry , Seawater/microbiology , Anti-HIV Agents/isolation & purification , Anti-HIV Agents/pharmacology , Cell Line , Chaetomium/metabolism , Genes, Reporter/drug effects , Humans , Magnetic Resonance Spectroscopy , Molecular Conformation , Phenols/chemistry , Phenols/isolation & purification , Phenols/pharmacology , Spectrometry, Mass, Electrospray IonizationABSTRACT
Two new cytochalasans with a rare 6/6/5/5/7 pentacyclic ring system, named chaetoconvosins C-D (1: -2: ), together with two known congeners (3: -4: ), were isolated from the fermentation of an endophytic fungus, Chaetomium sp. SG-01, harbored in the fibrous roots of Schisandra glaucescens Diels. Their structures including the absolute configuration were elucidated by extensive spectroscopic (HRESIMS, NMR, and ECD) and X-ray crystallographic analyses. The TRAIL-resistance-overcoming activity of 1: -4: in a TRAIL-resistant HT29 colorectal cancer cell line was evaluated, which revealed that co-treatment of 1: -4: at 50 µM with TRAIL (150 ng/mL) reduced the HT29 cell viability by 19.0%, 24.1%, 17.9%, and 15.5%, respectively, compared to treatment with 1: -4: alone.
Subject(s)
Alkaloids , Chaetomium , Chaetomium/chemistry , Chaetomium/metabolism , Crystallography, X-Ray , Magnetic Resonance Spectroscopy , Cytochalasins/pharmacology , Cytochalasins/chemistry , Molecular StructureABSTRACT
Two novel cytochalasans, armochaetoglasin J (1) and armochaetoglasin K (2), along with 14 known analogues (3-16) were isolated from Chaetomium globosum. Their structures were elucidated by HRESIMS, NMR spectroscopy, single-crystal X-ray crystallography, and ECD spectra. Armochaetoglasins J and K were found to be inactive against the HepG2, HT-29, K562, HL-60, and A549 cancer cell lines.
Subject(s)
Chaetomium , Chaetomium/chemistry , Crystallography, X-Ray , Cytochalasins/chemistry , HL-60 Cells , HumansABSTRACT
Rubichaetoglobin A (1), a new cytochalasan alkaloid, together with nine closely related known ones (2-10), were isolated from the ethyl acetate extracts of the endophytic fungus Chaetomium tectifimeti S104 harbored in the root of Rubia podantha Diels. Their structures were elucidated based on comprehensive spectroscopic analysis. All isolated compounds were tested for cytotoxic, antibacterial, and nitric oxide inhibitory activities. The results showed that 2, 4, and 5 possessed moderate cytotoxicity against MDA-MB-231 cells with the IC50 values of 19.14, 11.43, and 10.27 µM, respectively.