Marcytoglobosins A and B, Cytochalasans From a Marine Sponge Associated Chaetomium globosum 162105 Fungus.

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 25 µg/mL.

Chae-type cytochalasans from coculture of Aspergillus flavipes and Chaetomium globosum.

Cocultivation of the high cytochalasan-producing fungi Aspergillus flavipes and Chaetomium globosum resulted in the isolation of 11 undescribed Chae-type cytochalasans. Their structures were determined by spectroscopic data and NMR data calculations. Asperchaetoglobin A (1) was the first Chae-type cytochalasan possessing an unprecedented nitrogen bridge between C-17 and C-20 to generate a surprising 5/6/12/5 multiple ring system; asperchaetoglobins B and C (2 and 3) displayed higher oxidation with an additional epoxide at the thirteen-member ring; asperchaetoglobin D (4) was the second Chae-type cytochalasin featuring a 5/6/12 tricyclic ring system. The cytotoxic activities against five human cancer cell lines and antibacterial activities against Staphylococcus aureus and Colon bacillus of selected compounds were evaluated in vitro.

Phytochemical Analysis and Antioxidant Activity of Endophytic Fungi Isolated from Dillenia indica Linn.

Endophytic fungi live symbiotically inside plants and are hidden source of natural bioactive molecules. The present study was carried out to investigate the phytochemical analysis and antioxidant activity of endophytic fungi isolated from the ethnomedicinal plant Dillenia indica L. The ethyl acetate crude extracts of the endophytic fungal strains were preliminarily evaluated for their phytochemical analysis, and the results showed the presence of alkaloids, flavonoids, phenolics, terpene, and saponins. The crude extracts of more than 60% of the isolates showed 50-90% antioxidant activity by DPPH and H2O2 assay. The inhibition percentage of ethyl acetate extracts ranges from 34.05 to 91.5%, whereas IC50 values vary from 72.2 to 691.14%. Among all the strains, Fomitopsis meliae crude extract showed a maximum inhibition percentage, i.e., 91.5%, with an IC50 value of 88.27 µg/mL. Chaetomium globosum showed significant activity having an inhibition percentage of 89.88% and an IC50 value of 74.44 µg/mL. The total phenolic and flavonoid content in the crude extract of Chaetomium globosum was 37.4 mg gallic acid equivalent (GAE)/g DW and 31.0 mg quercetin equivalent (GAE)/g DW. GC-MS analysis of crude extract of C. globosum revealed different compounds, such as squalene; butanoic acid, 2-methyl-; hexadecanoic acid; 2-propanone, 1-phenyl-; 5-oxo-pyrrolidine-2-carboxylic acid methyl ester; 9,12-octadecadienoic acid (z)- etc. Many of these belong to phenolics, which are natural antioxidant compounds. The findings suggested that endophytic fungi associated with Dillenia indica L. can be a potential source of novel antioxidant compounds.

Chaetomium globosum: Spotting a scarce saprophyte in bacterial-fungal co-infection of the sinuses in a post-COVID-19 patient.

Atypical fungal co-infections in post-COVID-19 patients may have been underreported due to limited diagnostic methods. We present a case of Chaetomium globosum sinusitis in a 55-year-old post-COVID-19 patient with pain in the left side of the face, mimicking rhino-cerebral mucormycosis. CT-paranasal sinuses showed mucosal thickening of left paranasal sinuses, biopsy of which grew a velvety, white colony. It was confirmed as Chaetomium globosum. The patient responded to oral Posaconazole therapy for three months. Prompt identification of atypical fungal agents is critical for appropriate treatment.

Chemical constituents from the medicinal herb-derived fungus Chaetomium globosum Km1226.

BACKGROUND: Endophytic fungi have proven to be a rich source of novel natural products with a wide-array of biological activities and higher levels of structural diversity. RESULTS: Chemical investigation on the liquid- and solid-state fermented products of Chaetomium globosum Km1226 isolated from the littoral medicinal herb Atriplex maximowicziana Makino resulted in the isolation of compounds 1-14. Their structures were determined by spectroscopic analysis as three previously undescribed C13-polyketides, namely aureonitol C (1), mollipilins G (2), and H (3), along with eleven known compounds 4-14. Among these, mollipilin A (5) exhibited significant nitric oxide production inhibitory activity in LPS-induced BV-2 microglial cells with an IC50 value of 0.7 ± 0.1 µM, and chaetoglobosin D (10) displayed potent anti-angiogenesis property in human endothelial progenitor cells (EPCs) with an IC50 value of 0.8 ± 0.3 µM. CONCLUSIONS: Three previously unreported compounds 1-3 were isolated and identified. Mollipilin A (5) and chaetoglobosin D (10) could possibly be developed as anti-inflammatory and anti-angiogenic lead drugs, respectively.

Characterization and development of transcriptome-derived novel EST-SSR markers to assess genetic diversity in Chaetomium globosum.

Chaetomium globosum Kunze, an internationally recognized biocontrol fungus. It mycoparasitizes various plant pathogens and produce antifungal metabolites to suppress the growth of pathogenic fungi. Lack of detailed genome level diversity studies has delimited the development and utilization of potential C. globosum strains. The present study was taken to reveal the distribution, identification, and characterization of expressed sequence tag-simple sequence repeats (EST-SSRs) in C. globosum. RNA-Seq experiment was performed for C. globosum potential isolate Cg2 (AY429049) using Illumina HiSeq 2500. Reference-guided de novo assembly yielded 45,582 transcripts containing 27,957 unigenes. We generated a new set of 8485 EST-SSR markers distributed in 5908 unigene sequences with one SSR locus distribution density per 6.1 kb. Six distinct classes of SSR repeat motifs were identified. The most abundant were mononucleotide repeats (51.67%), followed by tri-nucleotides (36.61%). Out of 5034 EST-SSR primers, 50 primer pairs were selected and validated for the polymorphic study of 15 C. globosum isolates. Twenty-two SSR markers showed average genetic polymorphism among C. globosum isolates. The number of alleles (Na) per marker ranges from 2 to 4, with a total of 74 alleles detected for 22 markers with a mean polymorphism information content (PIC) value of 0.4. UPGMA hierarchical clustering analysis generated three main clusters of C. globosum isolates and exhibited a lower similarity index range from 0.59 to 0.85. Thus, the newly developed EST-SSR markers could replace traditional methods for determining diversity. The study will also enhance the genomic research in C. globosum to explore its biocontrol potential against phytopathogens. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03794-7.

Novel chlorinated and nitrogenated azaphilones with cytotoxic activities from the marine algal-derived fungus Chaetomium globosum 2020HZ23.

Two novel chlorinated and nitrogenated azaphilones, namely N-butyl-2-aza-2-deoxychaetoviridin A (1) and N-hexyl-2-aza-2-deoxychaetoviridin A (2), along with a previously identified analogue, chaetoviridin A (3), were successfully obtained from Chaetomium globosum 2020HZ23, a marine algal-sourced endophytic fungus. The planar structures as well as the absolute configurations of these new metabolites were determined utilizing a synergistic approach that involved both spectroscopic techniques (1D/2D NMR and HRESIMS) and Density Functional Theory (DFT) calculations. Each compound was subject to in vitro cytotoxicity evaluation toward the A549 cancer cell line. Both compounds 1 and 2 demonstrated significant cytotoxicity, as evidenced by their respective IC50 values of 13.6 and 17.5 µM. Furthermore, 1 and 2 demonstrated potent cell migration inhibition, which elevated with increasing dose concentration. In contrast, compound 3 exhibited less cytotoxic activity relative to 1 and 2, suggesting that the cytotoxic potency escalates with N-substitution at the C-2 position and the introduction of a side chain. This finding could offer implications for future studies aimed at designing and refining lead compounds within this class.

Identification and Characterization of Two Novel Extracellular ß-Glucanases from Chaetomium globosum against Fusarium sporotrichioides.

Chaetomium globosum can inhibit the growth of fusarium by means of their extracellular proteins. Two novel ß-glucanases, designated Cgglu17A and Cgglu16B, were separated from the supernatant of C. globosum W7 and verified to have the ability to hydrolyze cell walls of Fusarium sporotrichioides MLS-19. Cgglu17A (397 amino acids) was classified as glycoside hydrolase family 17 while Cgglu16B belongs to the family16 (284 amino acids). Recombinant protein Cgglu17A was successfully expressed in Escherichia coli, and the enzymes were purified by affinity chromatography. Maximum activity of Cgglu17A appeared at the pH 5.5 and temperature 50 °C, but Cgglu16B shows the maximum activity at the pH 5.0 and temperature 50 °C. Most of heavy metal ions had inhibition effect on the two enzymes, but Cgglu17A and Cgglu16B were respectively activated by Ba2+ and Mn2+. Cgglu17A exhibited high substrate specificity, almost only catalyzing the cleavage of ß-1,3-glycosidic bond, in various polysaccharose, to liberate glucose. However, Cgglu16B showed high catalytic activities to both ß-1,3-glycosidic and ß-1,3-1,4-glycosidic bonds. Cgglu17A was an exo-glucanase, but Cgglu16B was an endo-glucanase based on hydrolytic properties assay. Both of two enzymes showed potential antifungal activity, and the synergistic effect was observed in the germination experiment of pathogenic fungus. In conclusion, Cgglu17A (exo-1,3-ß-glucanase) and Cgglu16B (endo-1,3(4)-ß-glucanase) were confirmed to play a key role in the process of C. globosum controlling fusarium and have potential application value on industry and agriculture for the first time.

Biomolecules from Chaetomium globosum Possessing Antimicrobial Compounds Potentially Inhibits Fusarium Wilt of Tomato.

Wilt disease caused by Fusarium solani, a soil-borne plant pathogenic fungus, is a serious disease in tomato causing economic losses. In the present study, among the nine isolates of Chaetomium globosum Kunze (Chg1-Chg9), screened against F. solani No. Fs-1, Chg2 exhibited the maximum inhibition (49.2 %), followed by the isolates Chg6 (47.4%) and Chg1 (46.3%) in dual culture. Further, the crude secondary metabolites from these three isolates showed maximum reduction of the mycelial growth of Fs-1 compared to control. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of the metabolites from Chg2 revealed the presence of major compounds, viz., benzothiazole, 2-(2-hydroxyethylthio) (7.51%); 9,12,15- octadecatrienoic acid, 2,3-bis[(trimethylsilyl)oxy] propyl ester (3.13%); and hexadecanoic acid, 1- (hydroxymethyl)-1,2-ethanediyl ester (2.69%). Fourier transform infrared (FTIR) spectroscopy revealed the presence of alcohol, secondary amine, aliphatic primary amine, carboxylic acid, allene, conjugated ketone, imine/oxime, sulphate, and halo compound groups with a weak to strong range of intensity. Pure compound of benzothiazole @ 5000 ppm exhibited higher antagonistic activity of Fs-1which decreased at lower concentration. In pot culture experiment, dipping tomato seedlings cv. PKM1 in 2% ethyl acetate-fractionated biomolecules of Chg2 recorded a minimum disease incidence of 20.0%, whereas seedlings dipped in the culture filtrate of Chg2 showed a disease incidence of 26.6% compared to control (86.6%). Besides, these seedlings treated with the culture filtrate showed the highest plant height of 37.68 cm and the maximum number of leaves and flowers (39.6 and 5.48, respectively), followed by those treated with the biomolecules of Chg2 (C. globosum) and the culture filtrate of T. asperellum. The results revealed that the antifungal efficacy of C. globosum Chg2 is due to the presence of antimicrobial metabolites including benzothiazole. Exploring the use of this novel antifungal compound in the management of plant diseases is highly warranted.

Improved Chrysin Production by a Combination of Fermentation Factors and Elicitation from Chaetomium globosum.

Flavonoids encompass a heterogeneous group of secondary metabolites with exceptional health benefits. Chrysin, a natural dihydroxyflavone, possesses numerous bioactive properties, such as anticancer, antioxidative, antidiabetic, anti-inflammatory, etc. However, using traditional sources of chrysin involves extracting honey from plants, which is non-scalable, unsustainable, and depends on several factors, including geography, climatic conditions, and the season, which limits its production at a larger scale. Recently, microbial production of desirable metabolites has garnered attention due to the cost-effectiveness, easy scale-up, sustainability, and low emission of waste. We previously reported for the first time the chrysin-producing marine endophytic fungus Chaetomium globosum, associated with a marine green alga. To extend our understanding of chrysin biosynthesis in C. globosum, in the present study, we have assessed the presence of flavonoid pathway intermediates in C. globosum extracts using LC-MS/MS. The presence of several key metabolites, such as dihydrokaempferol, chalcone, galangin, baicalein, chrysin, p-Coumaroyl-CoA, and p-Cinnamoyl-CoA, indicates the role of flavonoid biosynthesis machinery in the marine fungus. Further, we have aimed to enhance the production of chrysin with three different strategies: (1) optimizing the fermentation parameters, namely, growth medium, incubation time, pH, and temperature; (2) feeding key flavonoid pathway intermediates, i.e., phenylalanine and cinnamic acid; (3) elicitation with biotic elicitors, such as polysaccharide, yeast extract, and abiotic elicitors that include UV radiation, salinity, and metal stress. The combined effect of the optimized parameters resulted in a 97-fold increase in the chrysin yield, resulting in a fungal cell factory. This work reports the first approach for enhanced production of chrysin and can serve as a template for flavonoid production enhancement using marine endophytic fungi.

Corrigendum: Temporal transcriptome of tomato elucidates the signaling pathways of induced systemic resistance and systemic acquired resistance activated by Chaetomium globosum.

[This corrects the article DOI: 10.3389/fgene.2022.1048578.].

Biological control of Fusarium crown rot of wheat with Chaetomium globosum 12XP1-2-3 and its effects on rhizosphere microorganisms.

Chaetomium globosum is a common plant endophytic fungi that exhibits great biocontrol potential in plant disease. Fusarium crown rot (FCR) is an important disease in wheat that seriously threatens wheat production worldwide. The control effect of C. globosum against wheat FCR remains unclear. In this study, we introduced an identified C. globosum 12XP1-2-3 and tested its biological control potential against wheat FCR. The hypha and fermentation broth exhibited an antagonistic effect against Fusarium pseudograminearum. Results from indoor experiments showed that C. globosum 12XP1-2-3 might delay the onset of symptoms of brown stem base and significantly reduced the disease index (37.3%). Field trials showed that wheat seeds coated with a spore suspension of 12XP1-2-3 grew better than the control seeds, had control effects of 25.9-73.1% on FCR disease, and increased wheat yield by 3.2-11.9%. Analysis of rhizosphere microorganisms revealed that seeds coated with C. globosum ('Cg' treatment) had a greater effect on fungal rather than on bacterial alpha diversity and may improve the health state of rhizosphere microorganisms, as reflected by the significantly increased fungal Shannon index at Feekes 11 and the increased complexity of the bacterial co-occurrence network but decreased complexity of the fungal network. Moreover, the accumulation of beneficial bacteria such as Bacillus and Rhizobium at Feekes 3, and Sphingomonas at Feekes 7 in the 'Cg' treatment may be the important contributions to healthier wheat growth state, significantly reduced relative abundance of Fusarium at Feekes 11, and reduced occurrence of FCR disease. These results provide a basis for further research on the mechanism of action of C. globosum and its application in the biological control of FCR in the field.

Infective endocarditis caused by Chaetomium globosum.

Chaetomium globosum is a dematiaceous, filamentous fungus belonging to the large genus saprobic ascomycetes and is rarely involved in human infection. We present the case of a 25-year-old man undergoing tricuspid valve replacement due to recurrent prosthetic ring endocarditis. Initially, it was considered culture-negative endocarditis; however, the diagnosis of Chaetomium globosum could only be provided by DNA isolation of the mold isolate grown in culture and the valve tissue samples taken from the patient. This report describes the first documented tricuspid endocarditis caused by Chaetomium species and discusses the importance of molecular tools to enhance the diagnostic process in culture-negative endocarditis, especially for fastidious and nonculturable microorganisms.

Chaetomium globosum D5 confers salinity tolerance on Paeonia lactiflora Pall.

Plants will interact with beneficial endophytic fungi to increase resistance under environmental stress. Among these stresses, salt stress poses one of the major threats to plant growth worldwide. We have studied the response mechanism of Chaetomium globosum D5, a salt-tolerant fungus isolated from the roots of Paeonia lactiflora under salt stress, and its mechanism of action in helping P. lactiflora alleviate salt stress. In our study, high levels of salt inhibit growth, whereas low levels promote the growth of C. globosum D5, which resists salt stress by forming dense hyphae and producing more pigments, soluble proteins, and antioxidants. Under salt stress, growth and photosynthesis of P. lactiflora are inhibited, and they are subjected to osmotic stress, oxidative stress, and ionic stress. C. globosum D5 could help P. lactiflora promote growth and photosynthesis by increasing the uptake of nitrogen and phosphorus and increasing the accumulation of the carbon and photosynthetic pigments, help P. lactiflora alleviate osmotic stress by increasing the accumulation of proline, help P. lactiflora alleviate ion stress by reducing Na+ and increasing K+/Na+, Ca2+/Na+ and Mg2+/Na + ratios in P. lactiflora roots and leaves. In summary, joint action between P. lactiflora and C. globosum D5 is responsible for mitigating damage caused by P. lactiflora under salt stress. We first investigate the interaction between the fungus and P. lactiflora under salt stress, providing a theoretical basis for further investigations into the mechanisms of P. lactiflora's response to salt stress and its promotion in coastal areas.

Identification of a Novel Pleiotropic Transcriptional Regulator Involved in Sporulation and Secondary Metabolism Production in Chaetomium globosum.

Chaetoglobosin A (CheA), a well-known macrocyclic alkaloid with prominently highly antimycotic, antiparasitic, and antitumor properties, is mainly produced by Chaetomium globosum. However, a limited understanding of the transcriptional regulation of CheA biosynthesis has hampered its application and commercialization in agriculture and biomedicine. Here, a comprehensive study of the CgXpp1 gene, which encodes a basic helix-loop-helix family regulator with a putative role in the regulation of fungal growth and CheA biosynthesis, was performed by employing CgXpp1-disruption and CgXpp1-complementation strategies in the biocontrol species C. globosum. The results suggest that the CgXpp1 gene could be an indirect negative regulator in CheA production. Interestingly, knockout of CgXpp1 considerably increased the transcription levels of key genes and related regulatory factors associated with the CheA biosynthetic. Disruption of CgXpp1 led to a significant reduction in spore production and attenuation of cell development, which was consistent with metabolome analysis results. Taken together, an in-depth analysis of pleiotropic regulation influenced by transcription factors could provide insights into the unexplored metabolic mechanisms associated with primary and secondary metabolite production.

Functional Chitosan-Calcium Carbonate Coatings for Enhancing Water and Fungal Resistance of Paper Materials.

The objective of this study was to increase the water resistance of paper while providing fungal resistance using a bio-based coating made from chitosan. The water resistance was improved through the surface control of roughness using modified calcium carbonate particles. The higher the quantity of particles in the film-forming solution, the higher the surface hydrophobicity of the paper. The addition of particles was found to counterbalance the chitosan hydrophilicity through the control of the coatings' penetration in the paper bulk. As a consequence, the wetting time and liquid water resistance were enhanced. The antifungal activity of the film-forming solutions and coated paper was also investigated against the growth of Chaetomium globosum, which was selected as a model strain able to contaminate paper materials. The results reveal that the antifungal activity of chitosan was improved by a possible synergic effect with the bicarbonate ions from the mineral particles.

Temporal transcriptome of tomato elucidates the signaling pathways of induced systemic resistance and systemic acquired resistance activated by Chaetomium globosum.

C. globosum is an endophytic fungus, which is recorded effective against several fungal and bacterial diseases in plants. The exclusively induce defense as mechanism of biocontrol for C. globosum against phyto-pathogens is reported. Our pervious study states the effectiveness of induced defense by C. globosum (Cg), in tomato against Alternaria solani. In this study the temporal transcriptome analysis of tomato plants after treatment with C. globosum was performed for time points at 0 hpCi, 12 hpCi, 24 hpCi and 96 phCi. The temporal expression analysis of genes belonging to defense signaling pathways indicates the maximum expression of genes at 12 h post Cg inoculation. The sequential progression in JA signaling pathway is marked by upregulation of downstream genes (Solyc10g011660, Solyc01g005440) of JA signaling at 24 hpCi and continued to express at same level upto 96 hpCi. However, the NPR1 (Solyc07g040690), the key regulator of SA signaling is activated at 12 h and repressed in later stages. The sequential expression of phenylpropanoid pathway genes (Solyc09g007920, Solyc12g011330, Solyc05g047530) marks the activation of pathway with course of time after Cg treatment that results in lignin formation. The plant defense signaling progresses in sequential manner with time course after Cg treatment. The results revealed the involvement of signaling pathways of ISR and SAR in systemic resistance induced by Cg in tomato, but with temporal variation.

Armochaetoglasins L and M, new cytochalasans from an arthropod-derived fungus Chaetomium globosum.

Armochaetoglasins L (1) and M (2), two new cytochalasans, were isolated from the EtOAc extract of an arthropod-derived fungus Chaetomium globosum. Armochaetoglasin L (1) is a rare 19,20-seco-chaetoglobosin. Their structures were elucidated by NMR spectroscopy and comparison of their electronic circular dichroism (ECD) data. Compounds 1 and 2 were evaluated for anti-inflammatory activity against the NO production by using LPS-stimulated murine macrophage RAW264.7 cells and antibacterial activity against three drug-resistant microbial pathogens.

Pro-angiogenic New Chloro-Azaphilone Derivatives From the Hadal Trench-Derived Fungus Chaetomium globosum YP-106.

Five new chloro-azaphilones, chaetofanixins A-E (1-5), and five known analogs (6-10) were isolated and identified from the hadal trench-derived fungus Chaetomium globosum YP-106. The structure of chaetofanixin E (5) is unique and interesting, bearing a highly rigid 6/6/5/3/5 penta-cyclic ring system, which is first encountered in natural products. The structures of these compounds, including absolute configurations, were determined based on the spectroscopic analysis, electronic circular dichroism (ECD) calculations, and analysis of biogenetic origins. Compounds 1-7 significantly promoted angiogenesis in a dose-dependent manner, and thus, these compounds might be used as promising molecules for the development of natural cardiovascular disease agents.

Effect of ultrasonic degradation on the physicochemical property and bioactivity of polysaccharide produced by Chaetomium globosum CGMCC 6882.

Similar to the enzymatic process, there might also be an active fragment in polysaccharides, how to obtain is important for investigating the bioactivity and pharmacological mechanism of polysaccharides. Presently, a Gynostemma pentaphyllum endophytic fungus Chaetomium globosum CGMCC 6882 polysaccharide [Genistein Combined Polysaccharide (GCP)] was degraded by ultrasonic treatment, two polysaccharide fragments of GCP-F1 and GCP-F2 were obtained. Physicochemical results showed that GCP-F1 and GCP-F2 had the same monosaccharide composition of arabinose, galactose, glucose, xylose, mannose, and glucuronic acid as compared to GCP with slightly different molar ratios. However, weight-average molecular weights of GCP-F1 and GCP-F2 decreased from 8.093 × 104 Da (GCP) to 3.158 × 104 Da and 1.027 × 104 Da, respectively. In vitro scavenging assays illustrated that GCP-F1 and GCP-F2 had higher antioxidant activity against 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide anions, and hydroxyl radical than GCP, the order was GCP < GCP-F1 < GCP-F2. Meanwhile, antibacterial tests showed that ultrasonic degradation increased the antibacterial activity of GCP-F1 as compared to GCP, but GCP-F2 almost lost its antibacterial activity with further ultrasound treatment. Changes in the antioxidant and antibacterial activities of GCP-F1 and GCP-F2 might be related to the variation of their molecular weights.