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Microbial Cell Factories May 2024Low targeting efficacy and high toxicity continue to be challenges in Oncology. A promising strategy is the glycosylation of chemotherapeutic agents to improve their...
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 IC of 0.89 mM, followed by RR with an IC of 1.67 mM, and 4MUR with an IC of 2.4 mM, whereas the respective aglycones displayed higher IC 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.
Topics: Humans; Pancreatic Neoplasms; Antineoplastic Agents; Cell Line, Tumor; Hypocreales; Rutin; Acremonium; Gemcitabine; Disaccharides
PubMed: 38720294
DOI: 10.1186/s12934-024-02395-0 -
Physiologia Plantarum 2024While endophytic fungi offer promising avenues for bolstering plant resilience against abiotic stressors, the molecular mechanisms behind this biofortification remain...
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.
Topics: Acremonium; Plant Growth Regulators; Homeostasis; Signal Transduction; Salt Tolerance; Oxidation-Reduction; Brassica napus; Salt Stress; Plant Proteins; Abscisic Acid; Photosynthesis
PubMed: 38695265
DOI: 10.1111/ppl.14328 -
International Journal of Food... Jun 2024Head 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...
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.
Topics: Avena; Phylogeny; Plant Diseases; China; Fusarium; DNA, Fungal; Acremonium
PubMed: 38657420
DOI: 10.1016/j.ijfoodmicro.2024.110715 -
Heliyon Apr 2024The water quality in Karachi (Pakistan) is uncertain due to the occurrence of fungi and other microorganisms. A total of twenty-five water samples were collected from...
The water quality in Karachi (Pakistan) is uncertain due to the occurrence of fungi and other microorganisms. A total of twenty-five water samples were collected from public places, educational institutes, hospitals, water supply systems and surface water of the canal of Karachi (Pakistan). The different fungal species including sp., , sp., Fusarium sp., sp., , sp. , sp. and sp. were isolated from these drinking water samples. However, the bacteria, microalgae and some other microorganisms were present in low concentrations. The reason for fungi infection and production of mycotoxicity depends upon various factors and the availability of their nutrients in filtration plants. The major threats to human health are fungal mycotoxicity which is responsible for carcinogenic and other lethal diseases. Mostly, the genus was dominated and isolated with a maximum of 88-98% of occurrence in the different samples of drinking water by the direct plate-spread method. For the control of fungi, various Physico-chemical coagulation treatments were used, but Potassium alum, clay pot, and hot water treatment disinfected effectively 69-70% removal of the fungi and its spore or mycelia from the water. In addition, it is concluded that drinking water purifications such as chlorination, filtration and lime did not eliminate thermophilic fungal spores or mycelia including , and from the water.
PubMed: 38576549
DOI: 10.1016/j.heliyon.2024.e28926 -
Journal of the Science of Food and... Apr 2024Most microorganisms that cause food decay and the lower the shelf life of foods are fungi. Nanotechnologies can combat various diseases and deal with the application of...
BACKGROUND
Most microorganisms that cause food decay and the lower the shelf life of foods are fungi. Nanotechnologies can combat various diseases and deal with the application of nanomaterial to target cells or tissues. In this study selenium nanoparticles (Se-NPs) were synthesized using ascorbic acid and characterized by ultraviolet-visible spectroscopy, transmission electron microscopy (TEM), X-ray diffraction and zeta potential. The different concentrations of As/Se-NPs were tested against various fungi, including Alternaria linicola, Alternaria padwickii, Botrytis cinerea, Bipolaris sp., Cephalosporium acremonium, Fusarium moniliform and Fusarium semitectum. This study tested the influence of coated As/Se-NPs on healthy strawberry fruits and those infected with Botrytis cinerea during 16 days of storage, with regard to shelf life, decay percentage, weight loss, total titratable acidity percentage, total soluble solids content (TSS) and anthocyanin content.
RESULTS
Energy-dispersive X-ray analysis showed only two elements: selenium and oxygen. TEM images showed that the nanoparticles ranged in size between 26 to 39 nm and were rhombohedral in shape. Se-NPs showed antifungal activity against all tested fungi, the most effective being against Botrytis cinerea, Cephalosporium acremonium and Fusarium semitectum. During storage periods of strawberries fruits coated with As/Se-NPs, the shelf life was increased, and the number of decaying fruits was less than in control (uncoated) and coated infected fruits. The decline in weight loss was lower in coated fruits than in control fruits.
CONCLUSION
These findings demonstrated that As/Se-NPs could effectively maintain the postharvest quality of strawberries, even when the fruit was infected with B. cinerea. © 2024 Society of Chemical Industry.
PubMed: 38563620
DOI: 10.1002/jsfa.13502 -
Journal of Natural Products Apr 2024Seven new sugar alcohol-conjugated acyclic sesquiterpenes, acremosides A-G (-), were isolated from the cultures of the sponge-associated fungus sp. IMB18-086 cultivated...
Seven new sugar alcohol-conjugated acyclic sesquiterpenes, acremosides A-G (-), were isolated from the cultures of the sponge-associated fungus sp. IMB18-086 cultivated with heat-killed . The structures were determined by comprehensive analyses of 1D and 2D NMR spectroscopic data. The relative configurations were established by -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 (-) featured the linear sesquiterpene skeleton with a tetrahydrofuran moiety attached to a sugar alcohol. Acremosides A () and C-E (-) showed significant inhibitory activities against hepatitis C virus (EC values of 4.8-8.8 μM) with no cytotoxicity (CC of >200 μM).
Topics: Sesquiterpenes; Animals; Molecular Structure; Acremonium; Antiviral Agents; Porifera; Hepacivirus; Humans; Pseudomonas aeruginosa
PubMed: 38561238
DOI: 10.1021/acs.jnatprod.4c00015 -
Fungal Systematics and Evolution Jun 2023Three new genera, six new species, three combinations, six epitypes, and 25 interesting new host and / or geographical records are introduced in this study. New genera:...
Three new genera, six new species, three combinations, six epitypes, and 25 interesting new host and / or geographical records are introduced in this study. New genera: (based on ), and (based on ). New species: (from cooling pad water, USA, (on dead wood of sp., Netherlands), (on lichen on brick wall, Netherlands), (on moss growing on a wall, Netherlands), (from rockwool, USA), and (from hydroponic water, USA). New combinations: (based on ), (based on ), and (based on ). Epitypes: (from water, USA), (on leaves of , Netherlands), (on , parasitic on , Germany), (on needles of , Canada), (on twigs of , Ukraine), and (on decayed branch, Netherlands). Furthermore, the higher order phylogeny of three genera regarded as is resolved, namely (), (, ), and (, ), with being an older name for Crous PW, Akulov A, Balashov S, Boers J, Braun U, Castillo J, Delgado MA, Denman S, Erhard A, Gusella G, Jurjević Ž, Kruse J, Malloch DW, Osieck ER, Polizzi G, Schumacher RK, Slootweg E, Starink-Willemse M, van Iperen AL, Verkley GJM, Groenewald JZ (2023). New and Interesting Fungi. 6. : 109-156. doi: 10.3114/fuse.2023.11.09.
PubMed: 38545457
DOI: 10.3114/fuse.2023.11.09 -
Physiologia Plantarum 2024Proteins of the armadillo repeat gene family play important roles in plant pathogen response. Here, 169 armadillo (ARM) genes were identified in upland cotton (Gossypium...
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.
Topics: Phylogeny; Verticillium; Ascomycota; Gossypium; Salicylic Acid; Disease Resistance; Plant Diseases; Plant Proteins; Gene Expression Regulation, Plant; Acremonium
PubMed: 38511474
DOI: 10.1111/ppl.14259 -
Acta Tropica Jun 2024Animal 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...
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.
Topics: Animals; Trypanosomiasis, African; Trypanosoma congolense; Administration, Oral; Mice; Disease Models, Animal; Acremonium; Female; Parasitemia; Mice, Inbred BALB C
PubMed: 38494059
DOI: 10.1016/j.actatropica.2024.107185 -
Biotechnology Journal Mar 2024Acremonium chrysogenum is the major industrial producer of cephalosporin C (CPC), which is used as raw material for the production of significant cephalosporin...
Acremonium chrysogenum is the major industrial producer of cephalosporin C (CPC), which is used as raw material for the production of significant cephalosporin antibiotics. Due to the lack of diverse promoter elements, the development of metabolic engineering transformation is relatively slow, resulting in a limited improvement on CPC production. In this study, based on the analysis of the transcriptome profile, 27 candidate promoters were selected to drive the expression of the reporter genes. The promoter activities of this library ranged from 0.0075 to 101 times of the control promoter P . Simultaneously, a rapid screening method for potential bidirectional promoters was developed and 4 strong bidirectional promoters from 27 candidate options were identified and validated. Finally, the Golden Gate method was employed to combine promoter modules from the library with various target genes. Through a mixed transformation and screening process, high-yielding strains AG-6, AG-18, and AG-41 were identified, exhibiting an increase in CPC production of 30%, 35%, and 29%, respectively, compared to the control strain Ac-∆axl2:: eGFP. Therefore, the utilization of this promoter library offers a broader range of synthetic biology toolkits for the genetic engineering transformation of A. chrysogenum, thus establishing a solid foundation for the precise regulation of gene expression.
Topics: Cephalosporins; Transcriptome; Acremonium; Metabolic Engineering
PubMed: 38479986
DOI: 10.1002/biot.202300683