Cellulase and pectinase are degrading cellulosic and pectic substances that form plant cell walls and, thereby, they have a wide range of applications in the agro-industrial by-products recycling and food industries. In the current research, Mucor circinelloides and M. hiemalis strains were tested for their ability to produce cellulase and pectinase from tangerine peel by submerged fermentation. Experiments on five variables: temperature, pH, incubation period, inoculum size, and substrate concentration, were designed with a Box–Behnken design, as well as response surface methodology (RSM), and analysis of variance was performed. In addition, cellulase and pectinase were partially purified and characterized. At their optimum parameters, M. circinelloides and M. hiemalis afforded high cellulase production (37.20 U/mL and 33.82 U/mL, respectively) and pectinase (38.02 U/mL and 39.76 U/mL, respectively). The partial purification of M. circinelloides and M. hiemalis cellulase produced 1.73- and 2.03-fold purification with 31.12 and 32.02% recovery, respectively; meanwhile, 1.74- and 1.99-fold purification with 31.26 and 31.51% recovery, respectively, were obtained for pectinase. Partially purified cellulase and pectinase from M. circinelloides and M. hiemalis demonstrated the highest activity at neutral pH, and 70 and 50 °C, for cellulase and 50 and 60 °C, for pectinase, respectively. Moreover, 10 mM of K+ increased M. circinelloides enzymatic activity. The production of cellulase and pectinase from M. circinelloides and M. hiemalis utilizing RSM is deemed profitable for the decomposition of agro-industrial wastes.

Xylan is the primary hemicellulosic polymer found in lignocellulosic agricultural wastes and can be degraded by xylanase. In the current research, Mucor circinelloides and M. hiemalis were tested for their ability to produce xylanase from tangerine peel by submerged fermentation. Experiments on five variables were designed with Box–Behnken design and response surface methodology. Analysis of variance was exercised, the xylanase output was demonstrated with a mathematical equation as a function of the five factors, and the quixotic states for xylanase biosynthesis was secured. In addition, xylanase was partially purified, characterized, and immobilized on calcium alginate beads. The optimum parameters for xylanase production by M. circinelloides and M. hiemalis were consisted of incubation temperature (30 and 20°C), pH value (9 and 7) incubation period (9 and 9 days), inoculum size (3 and 3 mL), and substrate concentration (3 and 3 g/100 mL), respectively. M. circinelloides and M. hiemalis demonstrated the highest xylanase activities after RSM optimization, with 42.23 and 35.88 U/mL, respectively. The influence of single, interchange, and quadratic factors on xylanase output was investigated using nonlinear regression equations with significant R² and p values. The partial purification of M. circinelloides and M. hiemalis xylanase yielded 1.69‐ and 1.97‐fold purification, and 30.74 and 31.34% recovery with 292.08 and 240.15 U/mg specific activity, respectively. Partially purified xylanase from M. circinelloides and M. hiemalis demonstrated the highest activity at neutral pH and 60 and 50°C, respectively. The immobilized M. circinelloides and M. hiemalis xylanase retained 84.02 and 79.43% activity, respectively. The production of xylanase from M. circinelloides and M. hiemalis utilizing RSM is deemed profitable for the decomposition of the agro‐industrial wastes.

Breast, cervical, and ovarian cancers are among the most serious cancers and the main causes of mortality in females worldwide, necessitating urgent efforts to find newer sources of safe anticancer drugs. The present study aimed to evaluate the anticancer potency of mycoendophytic Alternaria tenuissima AUMC14342 ethyl acetate extract on HeLa (cervical cancer), SKOV-3 (ovarian cancer), and MCF-7 (breast adenocarcinoma) cell lines. The extract showed potent effect on MCF-7 cells with an IC50 value of 55.53 μg/mL. Cell cycle distribution analysis of treated MCF-7 cells revealed a cell cycle arrest at the S phase with a significant increase in the cell population (25.53%). When compared to control cells, no significant signs of necrotic or apoptotic cell death were observed. LC-MS/MS analysis of Alternaria tenuissima extract afforded the identification of 20 secondary metabolites, including 7-dehydrobrefeldin A, which exhibited the highest interaction score (−8.0156 kcal/mol) in molecular docking analysis against human aromatase. Regarding ADME pharmacokinetics and drug-likeness properties, 7-dehydrobrefeldin A, 4’-epialtenuene, and atransfusarin had good GIT absorption and water solubility without any violation of drug-likeness rules. These findings support the anticancer activity of bioactive metabolites derived from endophytic fungi and provide drug scaffolds and substitute sources for the future development of safe chemotherapy.

Staphylococcus and Candida are recognized as causative agents in numerous diseases, and the rise of multidrug-resistant strains emphasizes the need to explore natural sources, such as fungi, for effective antimicrobial agents. This study aims to assess the in vitro anti-staphylococcal and anti-candidal potential of ethyl acetate extracts from various soil-derived fungal isolates. The investigation includes isolating and identifying fungal strains as well as determining their antioxidative activities, characterizing their phenolic substances through HPLC analysis, and conducting in silico molecular docking assessments of the phenolics’ binding affinities to the target proteins, Staphylococcus aureus tyrosyl-tRNA synthetase and Candida albicans secreted aspartic protease 2. Out of nine fungal species tested, two highly potent isolates were identified through ITS ribosomal gene sequencing: Aspergillus terreus AUMC 15447 and A. nidulans AUMC 15444. Results indicated that A. terreus AUMC 15447 and A. nidulans AUMC 15444 extracts effectively inhibited S. aureus (concentration range: 25–0.39 mg/mL), with the A. nidulans AUMC 15444 extract demonstrating significant suppression of Candida spp. (concentration range: 3.125–0.39 mg/mL). The A. terreus AUMC 15447 extract exhibited an IC₅₀ of 0.47 mg/mL toward DPPH radical-scavenging activity. HPLC analysis of the fungal extracts, employing 18 standards, revealed varying degrees of detected phenolics in terms of their presence and quantities. Docking investigations highlighted rutin as a potent inhibitor, showing high affinity (−16.43 kcal/mol and −12.35 kcal/mol) for S. aureus tyrosyl-tRNA synthetase and C. albicans secreted aspartic protease 2, respectively. The findings suggest that fungal metabolites, particularly phenolics, hold significant promise for the development of safe medications to combat pathogenic infections.

Burn injuries, which significantly affect global public health, require effective treatment strategies tailored to varying severity. Fungi are considered a sustainable, easily propagated source for lead therapeutic discovery. In this study, we explored the burn wound healing potential of Aspergillus terreus through a combination of in vitro, in vivo, metabolite profiling, and in silico analysis. The in vitro scratch assays performed with human skin fibroblast cells showed promising wound healing activity. Furthermore, the burn-induced rats model showed a marked improvement in cutaneous wound healing, evidenced by an accelerated rate of wound closure and better skin regeneration after A. terreus extract treatment at 14 days. The results of this study demonstrated significant enhancements in wound closure and tissue regeneration in the treated rat model, surpassing the outcomes of standard treatments. This controlled healing process, evidenced by superior collagen synthesis and angiogenesis and confirmed by histopathological studies, suggests that A. terreus has potential beyond the traditionally studied fungal metabolites. The metabolite profiling of 27 bioactive compounds was further investigated by docking analysis for the potential inhibition of the NF-κB pathway, which has an important function in inflammation and wound repair. The compounds eurobenzophenone A (7), aspernolide D (16), asperphenalenone A (23), aspergilate D (15), kodaistatin A (18), and versicolactone A (14) showed the highest binding affinity to the target protein with a pose score of −16.86, −14.65, −12.65, −12.45, −12.19, and −12.08 kcal/mol, respectively. Drug-likeness properties were also conducted. The findings suggest the potential wound healing properties of A. terreus as a source for lead therapeutic candidate discovery.

Background/Objectives: Endophytic fungi represent an alternative source for resveratrol (RES) production. The present study aims to utilize mycoendophytic-derived resveratrol as a reducing agent for the synthesis of silver nanoparticles (AgNPs), in addition to further assay the cytotoxic activity of a RES-conjugated nanocarrier system toward human epidermoid carcinoma A-431 cells. Methods: Alternaria alternata AUMC 16209 was isolated from the stem of grapevine Vitis vinifera L. cultivar prime. Strain identification was achieved through morphological and molecular characterization using ITS sequencing. A. alternata AUMC 16209 exhibited RES production capability upon cultivation on PDB medium for seven days with a total of 8.25 mg/L as determined by HPLC. The crude RES was purified using flash chromatography followed by structure elucidation through ¹H and ¹³C NMR analyses. The purified RES was used for green synthesis of nanoparticles, acting as a reducing agent for silver ions. Results: Stable RES-AgNPs were fabricated at particle sizes ranging from 25 to 47 nm. RES-AgNPs observed a plasmon resonance absorption band at 415 nm with a negative zeta potential value of −38.5 mV. The crystalline structure of RES-AgNPs was addressed through X-ray diffraction analysis. FT-IR spectroscopy confirms the involvement of the functional –OH group and the aromatic C=C bond in the reduction and stabilization process. RES-AgNPs was more efficient to inhibit the cellular proliferation of human epidermoid carcinoma A-431 cells compared to RES alone. Conclusions: This report introduces for the first time an endophytic A. alternata as a sustainable source for RES production and emphasizes its potential for green synthesis of stable AgNPs with promising cytotoxic activity.