Sorbicillinoids are a class of fungal polyketides with diverse structures and distinguished bioactivities. Although remarkable progress has been achieved in their chemistry and biosynthesis, the efflux of sorbicillinoids is poorly understood. Here, we found MFS transporter AcsorT was responsible for the biosynthesis of sorbicillinoids in Acremonium chrysogenum. Combinatorial knockout and subcellular location demonstrated that the plasma membrane-associated AcsorT was responsible for the transportation of sorbicillinol and subsequent formation of oxosorbicillinol and acresorbicillinol C via the berberine bridge enzyme-like oxidase AcsorD in the periplasm. Homology modeling and site-directed mutation revealed that Tyr303 and Arg436 were the key residues of AcsorT, which was further explained by molecular dynamics simulation. Based on our study, it was suggested that AcsorT modulates sorbicillinoid production by coordinating its biosynthesis and export, and a transport model of sorbicillinoids was proposed in A. chrysogenum.

This study evaluated the effects of supplementing the diet of lactating cows with Acremonium terrestris culture (ATC) on milk production, serum antioxidant capacity, inflammatory indices, and serum lipid metabolomics. Over 90 days, 24 multiparous Chinese Holstein cows in mid-lactation (108 ± 10.4 days in milk, 637 ± 25 kg body weight, 30.23 ± 3.7 kg/d milk yield) were divided into either a control diet (CON) or a diet supplemented with 30 g of ATC daily. All the data were analyzed using Student\'s t test with SPSS 20.0 software. The results showed that compared with CON feeding, ATC feeding significantly increased milk yield, antioxidant capacity, and immune function. Lipidome screening identified 143 lipid metabolites that differed between the two groups. Further analysis using \"random forest\" machine learning revealed three glycerophospholipid serum metabolites that could serve as lipid markers with a predictive accuracy of 91.67%. This study suggests that ATC can be a useful dietary supplement for improving lactational performance in dairy cows and provides valuable insights into developing nutritional strategies to maintain metabolic homeostasis in ruminants.

Argemone mexicana belonging to family Papaveraceae is a traditional medicinal plant widely utilized by tribal people in India for treating various ailments like skin infections, wounds and inflammation. This plant is very rich in alkaloidal content, which has a great potential in the treatment of anti-inflammatory disorders. Therapeutically promising bioactive molecules are often produced by endophytic fungi associated with medicinal plants. In this investigation, endophytic fungi were isolated from various parts of A. mexicana and screened for alkaloidal content. Among these, one of the fungal isolate, Acremonium alternatum AMEF-5 producing maximum alkaloids showed significant anti-inflammatory activity. Fractionation of this crude fungal extract through column chromatography yielded eight fractions, which were further screened for anti-inflammatory activities. Fraction 3 exhibited significant anti-inflammatory activity by the inhibition of lipoxygenase enzyme (IC50 15.2 ± 0.09 µg/ml), scavenging of the nitric oxide radicals (IC50 11.38 ± 0.35 µg/ml), protein denaturation (IC50 14.93 ± 0.4 µg/ml), trypsin inhibition (IC50 12.06 ± 0.64 µg/ml) and HRBC stabilization (IC50 11.9 ± 0.22 µg/ml). The bioactive alkaloid in fraction 3 was identified as aconitine which was confirmed by UV, FTIR, HPLC, HRMS, 1H NMR, and 13C NMR analysis. This study demonstrates that endophytic fungi serve a potential source for sustainable production of therapeutically important alkaloids.

The fermentation of a soil-derived fungus Acremonium sp. led to the isolation of thirteen ascochlorin congeners through integrated genomic and Global Natural Product Social (GNPS) molecular networking. Among the isolated compounds, we identified two unusual bicyclic types, acremochlorins O (1) and P (2), as well as two linear types, acremochlorin Q (3) and R (4). Compounds 1 and 2 contain an unusual benzopyran moiety and are diastereoisomers of each other, the first reported for the ascochlorins. Additionally, we elucidated the structure of 5, a 4-chloro-5-methylbenzene-1,3-diol with a linear farnesyl side chain, and confirmed the presence of eight known ascochlorin analogs (6-13). The structures were determined by the detailed interpretation of 1D and 2D NMR spectroscopy, MS, and ECD calculations. Compounds 3 and 9 showed potent antibacterial activity against Staphylococcus aureus and Bacillus cereus, with MIC values ranging from 2 to 16 μg/mL.

BACKGROUND: Low targeting efficacy and high toxicity continue to be challenges in Oncology. A promising strategy is the glycosylation of chemotherapeutic agents to improve their pharmacodynamics and anti-tumoral activity. Herein, we provide evidence of a novel approach using diglycosidases from fungi of the Hypocreales order to obtain novel rutinose-conjugates therapeutic agents with enhanced anti-tumoral capacity.
RESULTS: Screening for diglycosidase activity in twenty-eight strains of the genetically related genera Acremonium and Sarocladium identified 6-O-α-rhamnosyl-β-glucosidase (αRβG) of Sarocladium strictum DMic 093557 as candidate enzyme for our studies. Biochemically characterization shows that αRβG has the ability to transglycosylate bulky OH-acceptors, including bioactive compounds. Interestingly, rutinoside-derivatives of phloroglucinol (PR) resorcinol (RR) and 4-methylumbelliferone (4MUR) displayed higher growth inhibitory activity on pancreatic cancer cells than the respective aglycones without significant affecting normal pancreatic epithelial cells. PR exhibited the highest efficacy with an IC50 of 0.89 mM, followed by RR with an IC50 of 1.67 mM, and 4MUR with an IC50 of 2.4 mM, whereas the respective aglycones displayed higher IC50 values: 4.69 mM for phloroglucinol, 5.90 mM for resorcinol, and 4.8 mM for 4-methylumbelliferone. Further, glycoconjugates significantly sensitized pancreatic cancer cells to the standard of care chemotherapy agent gemcitabine.
CONCLUSIONS: αRβG from S. strictum transglycosylate-based approach to synthesize rutinosides represents a suitable option to enhance the anti-proliferative effect of bioactive compounds. This finding opens up new possibilities for developing more effective therapies for pancreatic cancer and other solid malignancies.

While endophytic fungi offer promising avenues for bolstering plant resilience against abiotic stressors, the molecular mechanisms behind this biofortification remain largely unknown. This study employed a multifaceted approach, combining plant physiology, proteomic, metabolomic, and targeted hormonal analyses to illuminate the early response of Brassica napus to Acremonium alternatum during the nascent stages of their interaction. Notably, under optimal growth conditions, the initial reaction to fungus was relatively subtle, with no visible alterations in plant phenotype and only minor impacts on the proteome and metabolome. Interestingly, the identified proteins associated with the Acremonium response included TUDOR 1, Annexin D4, and a plastidic K+ efflux antiporter, hinting at potential processes that could counter abiotic stressors, particularly salt stress. Subsequent experiments validated this hypothesis, showcasing significantly enhanced growth in Acremonium-inoculated plants under salt stress. Molecular analyses revealed a profound impact on the plant\'s proteome, with over 50% of salt stress response proteins remaining unaffected in inoculated plants. Acremonium modulated ribosomal proteins, increased abundance of photosynthetic proteins, enhanced ROS metabolism, accumulation of V-ATPase, altered abundances of various metabolic enzymes, and possibly promoted abscisic acid signaling. Subsequent analyses validated the accumulation of this hormone and its enhanced signaling. Collectively, these findings indicate that Acremonium promotes salt tolerance by orchestrating abscisic acid signaling, priming the plant\'s antioxidant system, as evidenced by the accumulation of ROS-scavenging metabolites and alterations in ROS metabolism, leading to lowered ROS levels and enhanced photosynthesis. Additionally, it modulates ion sequestration through V-ATPase accumulation, potentially contributing to the observed decrease in chloride content.

Head blight (HB) of oat (Avena sativa) has caused significant production losses in oats growing areas of western China. A total of 314 isolates, associated with HB were collected from the major oat cultivating areas of Gansu, Qinghai, and Yunnan Provinces in western China. Based on morphological characters, the isolates were initially classified into three genera, as differentiation to species was a bit difficult. Taxonomic analysis of these isolates based on muti-gene phylogenetic analyses (ITS, TEF1, TUB2, and RPB2) revealed four known Fusarium species, F. proliferatum, F. avenaceum, F. poae, and F. sibiricum, and one Acremonium specie (A. sclerotigenum). In addition, a new genus Neonalanthamala gen. nov., similar to genus Nalanthamala was introduced herein with a new combination, Neonalanthamala graminearum sp. nov., to accommodate the HB fungus. The molecular clock analyses estimated the divergence time of the Neonalanthamala and Nalanthamala based on a dataset (ITS, TUB2, RPB2), and we recognized the mean stem ages of the two genera are 98.95 Mya, which showed that they evolved from the same ancestor. N. graminearum was the most prevalent throughout the surveyed provinces. Pathogenicity test was carried out by using two different methods: seed inoculation and head inoculation. Results showed that F. sibiricum isolates were the most aggressive on the seed and head. A. sclerotigenum isolates were not pathogenic to seeds, and were developed less symptoms to the head compared to other species. Data analyses showed that the correlation of the germination potential, germination index, and dry weight of seed inoculation and disease index of plant inoculation had a highly significant negative correlation (P < 0.001). These results showed that the development of HB might be predicted by seed tests for this species. A. sclerotigenum and N. graminearum causing HB are being firstly reported on oat in the world. Similarly, F. proliferatum, F. avenaceum, F. poae and F. sibiricum causing oat HB are firstly reported in China.

Seven new sugar alcohol-conjugated acyclic sesquiterpenes, acremosides A-G (1-7), were isolated from the cultures of the sponge-associated fungus Acremonium sp. IMB18-086 cultivated with heat-killed Pseudomonas aeruginosa. The structures were determined by comprehensive analyses of 1D and 2D NMR spectroscopic data. The relative configurations were established by J-based configuration analysis and acetonide derivatization. The absolute configurations were elucidated by the Mosher ester method and ECD calculations. The structures of acremosides E-G (5-7) featured the linear sesquiterpene skeleton with a tetrahydrofuran moiety attached to a sugar alcohol. Acremosides A (1) and C-E (3-5) showed significant inhibitory activities against hepatitis C virus (EC50 values of 4.8-8.8 μM) with no cytotoxicity (CC50 of >200 μM).

Proteins of the armadillo repeat gene family play important roles in plant pathogen response. Here, 169 armadillo (ARM) genes were identified in upland cotton (Gossypium hirsutum). Phylogenetic analysis grouped these into 11 subfamilies, with conserved protein structures within each subfamily. The results signify that the expansion of the gene family occurred via whole genome duplication and dispersed duplication. Expression profiling and network analysis suggest that GhARM144 may regulate cotton resistance to Verticillium dahliae. GhARM144 was upregulated in roots by V. dahliae infection or salicylic acid treatment. This upregulation indicates a negative regulatory role of GhARM144\' in the cotton immune responses, potentially by manipulating salicylic acid biosynthesis. Protein interaction studies found that GhARM144 associates with an osmotin-like protein, GhOSM34, at the plasma membrane. Silencing GhOSM34 reduced the resistance to V. dahliae, suggesting it may play a positive regulatory role. The results demonstrate that GhARM144 modulates cotton immunity through interaction with GhOSM34 and salicylic acid signalling. Further study of these proteins may yield insights into disease resistance mechanisms in cotton and other plants.

Animal African trypanosomosis (AAT) is an important global disease of livestock that causes economic losses of up to 4.5 billion US dollars per year. Thus, eliminating AAT in endemic countries will improve agricultural productivity and economic growth. To prevent AAT, vector control and the development of prophylactic drugs are crucial. Ascofuranone (AF) is a bioactive fungal compound with proven in vitro trypanocidal potency and in vivo treatment efficacy. However, the complex stereoselective synthesis of AF has prevented its cost-effective industrial production. Recently, a genetically modified strain of Acremonium egyptiacum fungus that produces a high yield of AF was developed. Therefore, we hypothesized that the oral administration of the AF-producing fungus itself may be effective against AAT. Hence, this study aimed to evaluate the prophylactic activity of orally administered dry-heat-sterilized A. egyptiacum against Trypanosoma congolense IL3000 infection using a mouse model. The survival rate was significantly prolonged (p = 0.009), and parasitemia was suppressed in all AF-fungus-treated groups (Group 1-9) compared with that in the untreated control group (Group 10). Hence, the trypanocidal activity of AF was retained after dry-heat-sterilization of the AF-producing fungus and that its oral administration effectively prevented AAT. Since AAT is endemic to rural areas with underdeveloped veterinary infrastructure, dry-heat-sterilized A. egyptiacum would be the most cost-effective potential treatment for AAT.