Combining the Elicitor Up-Regulated Production of Unusual Linear Diterpene-Derived Variants for an In-Depth Assessment of the Application Value and Risk of the Medicinal and Edible Basidiomycete Schizophyllum commune.

To better assess the practical value and avoid potential risks of the traditionally medicinal and edible basidiomycete Schizophyllum commune, which may arise from undescribed metabolites, a combination of elicitors was introduced for the first time to discover products from cryptic and low-expressed gene clusters under laboratory cultivation. Treating S. commune NJFU21 with the combination of five elicitors led to the upregulated production of a class of unusual linear diterpene-derived variants, including eleven new ones (1-11), along with three known ones (12-14). The structures and stereochemistry were determined by 1D and 2D NMR, HRESIMS, ECD, OR and VCD calculations. Notably, the elongation terminus of all the diterpenes was decorated by an unusual butenedioic acid moiety. Compound 1 was a rare monocyclic diterpene, while 2-6 possessed a tetrahydrofuran moiety. The truncated metabolites 4, 5 and 13 belong to the trinorditerpenes. All the diterpenes displayed approximately 70% scavenging of hydroxyl radicals at 50 µM and null cytotoxic activity at 10 µM. In addition, compound 1 exhibited potent antifungal activity against the plant pathogenic fungi Colletotrichum camelliae, with MIC values of 8 µg/mL. Our findings indicated that this class of diterpenes could provide valuable protectants for cosmetic ingredients and the lead compounds for agricultural fungicide development.

A new Schizophyllum commune strain as a potential biocontrol agent against blueberry root rot.

In recent years, blueberry root rot has been caused mainly by Fusarium commune, and there is an urgent need for a green and efficient method to control this disease. To date, research on Schizophyllum commune has focused on antioxidant mechanisms, reactive dye degradation, etc., but the mechanism underlying the inhibition of pathogenic microorganisms is still unclear. Here, the control effects of S. commune on F. commune and blueberry root rot were studied using adversarial culture, tissue culture, and greenhouse pot experiments. The results showed that S. commune can dissolve insoluble phosphorus and secrete various extracellular hydrolases. The results of hyphal confrontation and fermentation broth antagonism experiments showed that S. commune had a significant inhibitory effect on F. commune, with inhibition rates of 70.30% and 22.86%, respectively. Microscopy results showed distortion of F. commune hyphae, indicating that S. commune is strongly parasitic. S. commune had a significant growth-promoting effect on blueberry tissue-cultured seedlings. After inoculation with S. commune, inoculation with the pathogenic fungus, or inoculation at a later time, the strain significantly reduced the root rot disease index in the potted blueberry seedlings, with relative control effects of 79.14% and 62.57%, respectively. In addition, S. commune G18 significantly increased the antioxidant enzyme contents in the aboveground and underground parts of potted blueberry seedlings. We can conclude that S. commune is a potential biocontrol agent that can be used to effectively control blueberry root rot caused by F. commune in the field.

Allergic bronchopulmonary mycosis due to Schizophyllum commune in a patient with chronic hepatitis B.

INTRODUCTION: Schizophyllum commune (S. commune) is an opportunistic pathogenic fungus and can cause infection of the respiratory system in immunocompromised hosts. Allergic bronchopulmonary mycosis (ABPM) is the major disease caused by S. commune. However, identification of S. commune using routine mycological diagnostic methods is difficult. It is easy to make mistakes in diagnosis and treatment, resulting in deterioration of the disease. We report the first case of ABPM due to S. commune in a Chinese patient with chronic hepatitis B. CASE PRESENTATION: The patient presented cough, sputum and dyspnea for six months. The pathogen was missed during routine laboratory workup. We performed bronchoscopy examination and bronchoalveolar lavage. S. commune was identified by metagenomic next-generation sequencing (mNGS) of bronchial alveolar lavage fluid (BALF). Hence, the patient was immediately treated with 200 mg voriconazole twice daily (intravenous infusion) and 20 mg prednisone once a day (oral therapy), along with oral entecavir for hepatitis B. There was no recurrence of infection after the medication was discontinued. CONCLUSIONS: S. commune infection should be considered in the diagnosis of patients with refractory cough, sputum and dyspnea, especially in immunocompromised individuals. The mNGS technique is an effective supplementary technique for the diagnosis of S. commune infection, enabling precise clinical decision-making and appropriate treatment. Most patients have good prognosis with a combination of proper antifungal therapy and hormonal therapy.

Bioguided isolation, identification and bioactivity evaluation of anti-fatigue constituents from Schizophyllum commune.

This study aims to clarify the specific anti-fatigue components of Schizophyllum commune (S.commune) and analyze its potential anti-fatigue mechanism. The main anti-fatigue active ingredient of S.commune was locked in n-butanol extract (SPE-n) by activity evaluation. Twelve compounds were identified by high performance liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS). The anti-fatigue effect of morusin is the most predominant among these 12 ingredients. The determination of biochemical indices showed that morusin could increase liver glycogen reserves, improve the activity of antioxidant enzymes in liver, and reduce reactive oxygen species (ROS) content in muscle tissue, thereby reducing myocyte damage. Further studies revealed that morusin could reduce the level of oxidative stress by activating Nrf2/HO-1 pathway, thus alleviating the fatigue of mice caused by exhaustive exercise. The current findings provide a theoretical basis for the development of natural anti-fatigue functional food.

The regulatory network of the White Collar complex during early mushroom development in Schizophyllum commune.

Blue light is an important signal for fungal development. In the mushroom-forming basidiomycete Schizophyllum commune, blue light is detected by the White Collar complex, which consists of WC-1 and WC-2. Most of our knowledge on this complex is derived from the ascomycete Neurospora crassa, where both WC-1 and WC-2 contain GATA zinc-finger transcription factor domains. In basidiomycetes, WC-1 is truncated and does not contain a transcription factor domain, but both WC-1 and WC-2 are still important for development. We show that dimerization of WC-1 and WC-2 happens independent of light in S. commune, but that induction by light is required for promoter binding by the White Collar complex. Furthermore, the White Collar complex is a promoter of transcription, but binding of the complex alone is not always sufficient to initiate transcription. For its function, the White Collar complex associates directly with the promoters of structural genes involved in mushroom development, like hydrophobins, but also promotes the expression of other transcription factors that play a role in mushroom development.

Anti-Inflammatory Sesquiterpenes from Fruiting Bodies of Schizophyllum commune.

Schizophyllum commune, a fleshy fungus, is an important medicinal and food-homologous mushroom in China. In this work, eight undescribed sesquiterpenes schizomycins A-H (1-8) and one new meroterpenoid schizomycin I (9) together with three known analogues (10-12) were isolated from fruiting bodies of S. commune. Their planar structures were established by extensive spectroscopic and mass spectrometric data. The absolute configurations of compounds 1, 2, and 4 were determined by single crystal X-ray diffraction, and compounds 3 and 5-9 were confirmed by electronic circular dichroism calculations. Anti-inflammatory activities of all isolated compounds were evaluated for their inhibitory effects on IL-6 and IL-1ß production in RAW 264.7 cells. Among them, compound 7 exhibited significant IL-6 inhibitory activity with an IC50 value of 3.6 µM. The results of molecular docking showed that compound 7 interacts with amino acid residues (Gly117, Lys118, Asp120, Thr166, and Try168) of the IL-6 receptor protein through hydrogen bonding.

Emulsion for stabilizing ß-carotene and curcumin prepared directly using a continuous phase of polysaccharide-rich Schizophyllum commune fermentation broth.

In this study, we examined the effect of Schizophyllum commune fermentation broth (SCFB) rich in polysaccharides (SCFP) on the stability and bioaccessibility of ß-carotene and curcumin. An SCFB-stabilized oil-in-water (o/w) emulsion (SCFBe) was prepared using SCFB as the continuous phase, and then evaluated for storage stability using an SCFP-based emulsion (SCFPe) as the control. The findings revealed that SCFBe is more stable at 60 °C than SCFPe, and stratification or droplet size varied at differing pH levels (3-9) and concentrations of Na+ (0.1-0.5 M) and Ca2+ (0.01-0.05 M). Since the absolute value of the zeta potential of SCFBe is much lower at 60 °C than that at 4 °C and 25 °C, a higher temperature (60 °C) may enhance the reactivity of polysaccharides and proteins in SCFB to improve the stability of SCFBe. Both the protective impact of SCFB on functional food molecules and their capacity to block lipid oxidation increased as polysaccharide content improved. The bioaccessibility of ß-carotene after in vitro simulated gastrointestinal digestion is 11.18 %-12.28 %, whereas that of curcumin is 31.64 %-33.00 %. By fermenting edible and medicinal fungi in liquid, we created a unique and environmentally friendly approach for getting food-grade emulsifiers without extraction.

Schizophyllan from Schizophyllum commune BRM 060008: Potential application as an inhibitor of lipase.

ß-D-glucan has significant implications in regulating lipid metabolism and preventing diseases associated with lipid accumulation. Schizophyllan (SPG) from Schizophyllum commune fungus is a commercially important ß-glucan with applications in the health food industry, pharmacy, and cosmetics. However, SPG was obtained by submerged culture of the wood-rotting and filamentous fungus S. commune BRM 060008, which may have been isolated from the Cerrado Biome of Brazil. In this study, to confirm that the polysaccharide produced by BRM 060008 strain fermentation was indeed (1→3)(1→6)-ß-D-glucan, it was purified and characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, high-performance size exclusion chromatography, nuclear magnetic resonance, and methylation analysis. The polysaccharide produced was identified as the ß-D-glucan expected with a high molecular weight (1.093 × 106 g/mol) and the thermogravimetric analysis indicated a maximum degradation temperature of ~324 °C and a 60 % residual weight, lower than commercial SPG. The molecular structure and thermal properties of the ß-D-glucan were similar to the commercial sample. Additionally, the in vitro pancreatic lipase inhibitory activity was evaluated, investigating anti-obesity and anti-lipidemic properties. The results showed unprecedented lipase inhibition activity to SPG prepared using the S. commune strain BRM 060008, making it promising for food and pharmaceutical applications.

Biological Synthesis, Characterization, and Therapeutic Potential of S. commune-Mediated Gold Nanoparticles.

Green-synthesized gold nanoparticles demonstrate several therapeutic benefits due to their safety, non-toxicity, accessibility, and ecological acceptance. In our study, gold nanoparticles (AuNPs) were created using an extracellular extract from the fungus Schizophyllum commune (S. commune). The reaction color was observed to be a reddish pink after a 24 h reaction, demonstrating the synthesis of the nanoparticles. The myco-produced nanoparticles were investigated using transmission electron microscopy (TEM), dynamic light scattering (DLS), and UV-visible spectroscopy. The TEM pictures depicted sphere-like shapes with sizes ranging from 60 and 120 nm, with an average diameter of 90 nm, which is in agreement with the DLS results. Furthermore, the efficiency of the AuNPs' antifungal and cytotoxic properties, as well as their production of intracellular ROS, was evaluated. Our findings showed that the AuNPs have strong antifungal effects against Trichoderma sp. and Aspergillus flavus at increasing doses. Additionally, the AuNPs established a dose-dependent activity against human alveolar basal epithelial cells with adenocarcinoma (A549), demonstrating the potency of synthesized AuNPs as a cytotoxic agent. After 4 h of incubation with AuNPs, a significant increase in intracellular ROS was observed in cancer cells. Therefore, these metallic AuNPs produced by fungus (S. commune) can be used as an effective antifungal, anticancer, and non-toxic immunomodulatory delivery agent.

Anaerobic production and biosynthesis mechanism of exopolysaccharides in Schizophyllum commune 20R-7-F01.

Exopolysaccharides (EPS) produced by microorganisms play a vital role in physiological and ecological processes. However, the mechanisms of EPS synthesis and release in anaerobic environments remain poorly understood. Here, we provide the first evidence of anaerobic EPS synthesis by the fungus Schizophyllum commune 20R-7-F01, isolated from coal-bearing sediments ~2.0 km below the seafloor. Under anaerobic conditions, the fungus exhibited significantly higher specific EPS production (1.57 times) than under aerobic conditions. Transcriptomic analysis revealed 2057 differentially expressed genes (DEGs) in the strain cultured anaerobically for 7 days compared to aerobically. Among these genes, 642 were significantly upregulated, while 1415 were significantly downregulated, mainly associated with carbon metabolism pathways. Genes involved in glycolysis and EPS synthesis, including hexokinase (HK), phosphoglucomutase (PGM), and (1 â†’ 3)-ß-glucan synthase (GLS), were significantly upregulated, while those related to the TCA cycle, respiratory chain, and pentose phosphate pathway were downregulated under anaerobic conditions. These findings highlight the oxygen-dependent regulation of EPS synthesis and suggest that EPS may serve as a key mechanism for fungal adaptation to anaerobic environments.

Functional characterization of a lytic polysaccharide monooxygenase from Schizophyllum commune that degrades non-crystalline substrates.

Lytic polysaccharide monooxygenases (LPMOs) are mono-copper enzymes that use O2 or H2O2 to oxidatively cleave glycosidic bonds. LPMOs are prevalent in nature, and the functional variation among these enzymes is a topic of great interest. We present the functional characterization of one of the 22 putative AA9-type LPMOs from the fungus Schizophyllum commune, ScLPMO9A. The enzyme, expressed in Escherichia coli, showed C4-oxidative cleavage of amorphous cellulose and soluble cello-oligosaccharides. Activity on xyloglucan, mixed-linkage ß-glucan, and glucomannan was also observed, and product profiles differed compared to the well-studied C4-oxidizing NcLPMO9C from Neurospora crassa. While NcLPMO9C is also active on more crystalline forms of cellulose, ScLPMO9A is not. Differences between the two enzymes were also revealed by nuclear magnetic resonance (NMR) titration studies showing that, in contrast to NcLPMO9C, ScLPMO9A has higher affinity for linear substrates compared to branched substrates. Studies of H2O2-fueled degradation of amorphous cellulose showed that ScLPMO9A catalyzes a fast and specific peroxygenase reaction that is at least two orders of magnitude faster than the apparent monooxygenase reaction. Together, these results show that ScLPMO9A is an efficient LPMO with a broad substrate range, which, rather than acting on cellulose, has evolved to act on amorphous and soluble glucans.

Antifungal Activity of Medicinal Mushrooms and Optimization of Submerged Culture Conditions for Schizophyllum commune (Agaricomycetes).

The main goal of the present study was the exploration of the antifungal properties of Agaricomycetes mushrooms. Among twenty-three tested mushrooms against A. niger, B. cinerea, F. oxysporum, and G. bidwellii, Schizophyllum commune demonstrated highest inhibition rates and showed 35.7%, 6.5%, 50.4%, and 66.0% of growth inhibition, respectively. To reveal culture conditions enhancing the antifungal potential of Sch. commune, several carbon (lignocellulosic substrates among them) and nitrogen sources and their optimal concentrations were investigated. Presence of 6% mandarin juice production waste (MJPW) and 6% of peptone in nutrient medium promoted antifungal activity of selected mushroom. It was determined that, extracts obtained in the presence of MJPW effectively inhibited the grow of pathogenic fungi. Moreover, the content of phenolic compounds in the extracts obtained from Sch. commune grown on MJPW was several times higher (0.87 ± 0.05 GAE/g to 2.38 ± 0.08 GAE/g) than the extracts obtained from the mushroom grown on the synthetic (glycerol contained) nutrient medium (0.21 ± 0.03 GAE/g to 0.88 ± 0.05 GAE/g). Flavonoid contents in the extracts from Sch. commune varied from 0.58 ± 0.03 to 27.2 ± 0.8 mg QE/g. Identification of phenolic compounds composition in water and ethanol extracts were provided by mass spectrometry analysis. Extracts demonstrate considerable free radical scavenging activities and the IC50 values were generally low for the extracts, ranging from 1.9 mg/ml to 6.7 mg/ml. All the samples displayed a positive correlation between their concentration (0.05-15.0 mg/ml) and DPPH radical scavenging activity. This investigation revealed that Sch. commune mushroom has great potential to be used as a source of antifungal and antioxidant substances.

ß-(1 → 3)(1 → 6)glucan from Schizophyllum commune 227E.32: High yield production via glucose/xylose co-metabolization.

A co-metabolization of xylose and glucose by Schizophyllum commune 227E.32 wild mushroom for exopolysaccharide (EPS) production is presented. Cultivations performed with S. commune 227E.32 at different xylose concentrations demonstrated that the concentration of 50 g·L-1 of xylose achieved the highest EPS production, around 4.46 g·L-1. Scale-up in a stirred tank reactor (STR) was performed. 10 % inoculum showed the highest cost/benefit ratio regarding sugar conversion and EPS production (Y P/S = 0.90 g·g-1), achieving 1.82 g·L-1 of EPS. Isolation, purification, and characterization were conducted with EPS produced in flasks and STR. GC-MS analysis showed glucose as main monosaccharide constituents for both isolates. 13C NMR and HSQC-edited showed that both EPS isolated consisted of a ß-D-Glcp (1 â†’ 3) main chain, partially substituted at O-6 with nonreducing ß-D-Glcp ends on every third residue, similar to ß-D-glucan isolated from S. commune basidiomes known as schizophyllan (SPG). The Mw was determined by GPC to 1.5 × 106 Da (flasks) and 1.1 × 106 Da (STR). AFM topographs revealed a semi-flexible appearance of the ß-D-glucan, consistent with the triple helical structures adopted by SPG and overall contour length consistent with a high molar mass.

Multiscalar electrical spiking in Schizophyllum commune.

Growing colonies of the split-gill fungus Schizophyllum commune show action potential-like spikes of extracellular electrical potential. We analysed several days of electrical activity recording of the fungus and discovered three families of oscillatory patterns. Very slow activity at a scale of hours, slow activity at a scale of 10 min and very fast activity at scale of half-minute. We simulated the spiking behaviour using FitzHugh-Nagume model, uncovered mechanisms of spike shaping. We speculated that spikes of electrical potential might be associated with transportation of nutrients and metabolites.

Unlocking the benefits of split gill mushroom: Chemical analysis and prebiotic properties of schizophyllan extract.

The edible split gill mushroom is considered both a nutritive and therapeutic superfood, as well as rich in schizophyllan and protein. Prebiotic properties and other biological effects distinguish the schizophyllan (ß-glucan). Thus, this research investigates the identity of the mushroom strain, the nutritional composition of this mushroom, and the schizophyllan extract for further analysis, including its prebiotic activity and so on. The experimental results revealed that this mushroom was identified as Schizophyllum commune, comprising more excellent carbohydrates, protein, crude fiber, lower fat, and no heavy metal detection. Moreover, this extract consisted of pharmaceutical hydrophobin (14.0-18.5 kDa), lectin protein (21-35 kDa), bioactive purpurin or red pigment, including the prebiotic ß-glucan stimulating the proliferation of probiotic bacteria isolated from yogurt. Therefore, both S. commune and the schizophyllan extract can be used as a prebiotic candidate, functional food, and nutraceutical product.

Successful management of nasopharyngitis caused by Schizophyllum commune in a captive cheetah (Acinonyx jubatus).

Herein, we describe the management of nasopharyngitis caused by Schizophyllum commune infection in a captive cheetah. Computed tomography revealed a nodule in the nasal cavity and pharynx, and an endoscopic biopsy was performed. As a result, the nodule was surgically resected because of a suspected carcinoma. However, the surgical specimen was histologically re-evaluated and a fungal granuloma was diagnosed. Sequence analysis of DNA from formalin-fixed, paraffin-embedded samples revealed S. commune infection. The cheetah was administered fluconazole orally for 73 days. However, the drug was ineffective and itraconazole was administered for 14 days. Symptoms such as nasal discharge and sneezing have completely resolved for 4 years.

Pneumonia caused by Schizophyllum commune in a patient with diabetes: A case report and comprehensive literature review.

RATIONALE: Schizophyllum commune (S. commune) is a basidiomycete bracket fungus that rarely causes invasive fungal infections. It is often misdiagnosed as other invasive fungal disease because of its atypical clinical features. Here we report a case of pneumonia due to S commune and review the relevant literature. PATIENT CONCERNS AND DIAGNOSES: A 55-year-old male with a history of diabetes and poor glycemic control presented with cough and sputum for half a month. Laboratory examination showed elevated peripheral blood eosinophils, bronchoalveolar lavage fluid eosinophils and increased serum total immunoglobulin E. Chest computed tomography revealed a gloved finger sign and consolidation in the middle lobe of the right lung and the upper lobe of the left lung. Bronchoscopy revealed thick white mucous plugs in the left lingular bronchus, which could be removed partially by suctioning. The culture of bronchoalveolar lavage fluid and bronchoscopy brush specimens grew cottony white mold in sabouraud dextrose agar. Pneumonia caused by S. commune was diagnosed based on clinical features and microbial methods. INTERVENTIONS AND OUTCOMES: Voriconazole combined with inhaled budesonide and formoterol (inhaled corticosteroids + long-acting ß-2 receptor agonist) were given, and his symptoms improved. The count of peripheral blood eosinophils and serum total immunoglobulin E decreased after 1 month. Repeated chest computed tomography showed remarkable improvement over the previous lesions. LESSONS: Although rarely reported, infections in the lungs caused by S commune should be reminded especially in patients with immunocompromised. This case illustrates the risk factors, clinical symptoms and imaging features of the pneumonia caused by S. commune. It also further highlights the diagnosis and treatment of this disease through reviewing relevant literature.