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.

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.

Histone acetylation modifications in filamentous fungi play a crucial role in epigenetic gene regulation and are closely linked to the transcription of secondary metabolite (SM) biosynthetic gene clusters (BGCs). Histone deacetylases (HDACs) play a pivotal role in determining the extent of histone acetylation modifications and act as triggers for the expression activity of target BGCs. The genus Chaetomium is widely recognized as a rich source of novel and bioactive SMs. Deletion of a class I HDAC gene of Chaetomium olivaceum SD-80A, g7489, induces a substantial pleiotropic effect on the expression of SM BGCs. The C. olivaceum SD-80A ∆g7489 strain exhibited significant changes in morphology, sporulation ability, and secondary metabolic profile, resulting in the emergence of new compound peaks. Notably, three polyketides (A1-A3) and one asterriquinone (A4) were isolated from this mutant strain. Furthermore, our study explored the BGCs of A1-A4, confirming the function of two polyketide synthases (PKSs). Collectively, our findings highlight the promising potential of molecular epigenetic approaches for the elucidation of novel active compounds and their biosynthetic elements in Chaetomium species. This finding holds great significance for the exploration and utilization of Chaetomium resources. KEY POINTS: • Deletion of a class I histone deacetylase activated secondary metabolite gene clusters. • Three polyketides and one asterriquinone were isolated from HDAC deleted strain. • Two different PKSs were reported in C. olivaceum SD-80A.

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.

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.

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.

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 RAW264.7 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.

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.

Microorganisms are a unique part of our ecosystem because they affect the survival of living organisms. Although pathogenic microorganisms could be detrimental to the plants, animals, and humans, beneficial microbes have provided significant improvement in the growth and development of living organisms. In this study, the fungus Chaetomium globosium was isolated from the medicinal tree Gingko biloba, and then incorporated into a polymerization system to fabricate chitosan/acrylamide/gold (CS/Am/Au) nanocomposite hydrogels. The as-prepared hydrogel displayed increased mechanical strength due to the reinforcement of Au (gold) nanocomposites within the hydrogel matrix. Also, the equilibrium pH responsive swelling rates of the hydrogels gradually increased as the pH increases due to partial acid and basic hydrolysis occurring in the hydrogel as well as formation of hydrogen bond. In addition, the hydrogel demonstrated promising antibacterial activities against selected gram-positive (Staphylococcus epidermidis and Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa) bacterial strains with an average MIC90 of 0.125 mg/mL at a dosage of 1.0 mg/L. The obtained results are quite promising towards resolving several health challenges and advancing the pharmaceutical industries.

Chaetomium globosum can inhibit the growth of fusarium by means of their extracellular proteins. Two novel β-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 β-1,3-glycosidic bond, in various polysaccharose, to liberate glucose. However, Cgglu16B showed high catalytic activities to both β-1,3-glycosidic and β-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-β-glucanase) and Cgglu16B (endo-1,3(4)-β-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.