Bioprospecting endophytic fungi for bioactive metabolites with seed germination promoting potentials.

There is an urgent need for new bioactive molecules with unique mechanisms of action and chemistry to address the issue of incorrect use of chemical fertilizers and pesticides, which hurts both the environment and the health of humans. In light of this, research was done for this work to isolate, identify, and evaluate the germination-promoting potential of various plant species' fungal endophytes. Zea mays L. (maize) seed germination was examined using spore suspension of 75 different endophytic strains that were identified. Three promising strains were identified through screening to possess the ability mentioned above. These strains Alternaria alternate, Aspergilus flavus, and Aspergillus terreus were isolated from the stem of Tecoma stans, Delonix regia, and Ricinus communis, respectively. The ability of the three endophytic fungal strains to produce siderophore and indole acetic acid (IAA) was also examined. Compared to both Aspergillus flavus as well as Aspergillus terreus, Alternaria alternata recorded the greatest rates of IAA, according to the data that was gathered. On CAS agar versus blue media, all three strains failed to produce siderophores. Moreover, the antioxidant and antifungal potentials of extracts from these fungi were tested against different plant pathogens. The obtained results indicated the antioxidant and antifungal activities of the three fungal strains. GC-Mass studies were carried out to determine the principal components in extracts of all three strains of fungi. The three strains' fungus extracts included both well-known and previously unidentified bioactive compounds. These results may aid in the development of novel plant growth promoters by suggesting three different fungal strains as sources of compounds that may improve seed germination. According to the study that has been given, as unexplored sources of bioactive compounds, fungal endophytes have great potential.

Gamma rays-assisted bacterial synthesis of bimetallic silver-selenium nanoparticles: powerful antimicrobial, antibiofilm, antioxidant, and photocatalytic activities.

BACKGROUND: Bimetallic nanoparticles (BNPs) has drawn a lot of attention especially during the last couple of decades. A bimetallic nanoparticle stands for a combination of two different metals that exhibit several new and improved physicochemical properties. Therefore, the green synthesis and design of bimetallic nanoparticles is a field worth exploring. METHODS: In this study, we present a green synthesis of silver nanoparticles (Ag NPs), selenium (Se) NPs, and bimetallic Ag-Se NPs using Gamma irradiation and utilizing a bacterial filtrate of Bacillus paramycoides. Different Techniques such as UV-Vis., XRD, DLS, SEM, EDX, and HR-TEM, were employed for identifying the synthesized NPs. The antimicrobial and antibiofilm activities of both the Ag/Se monometallic and bimetallic Ag-Se NPs were evaluated against some standard microbial strains including, Aspergillus brasiliensis ATCC16404, Candida albicans ATCC10231, Alternaria alternate EUM108, Fusarium oxysporum EUM37, Escherichia coli ATCC11229, Bacillus cereus ATCC15442, Klebsiella pneumoniae ATCC13883, Bacillus subtilis ATCC15442, and Pseudomonas aeruginosa ATCC6538 as a model tested pathogenic microbes. The individual free radical scavenging potentials of the synthesized Ag NPs, Se NPs, and bimetallic Ag-Se NPs were determined using the DPPH radical scavenging assay. The degradation of methylene blue (MB) dye in the presence of the synthesized Ag NPs, Se NPs, and bimetallic Ag-Se NPs was used to assess their photocatalytic behavior. RESULTS: According to the UV-Vis. spectrophotometer, the dose of 20.0 kGy that results in Ag NPs with the highest O.D. = 3.19 at 390 nm is the most effective dose. In a similar vein, the optimal dose for the synthesis of Se NPs was 15.0 kGy dose with O.D. = 1.74 at 460 nm. With a high O.D. of 2.79 at 395 nm, the most potent dose for the formation of bimetallic Ag-Se NPs is 15.0 kGy. The recorded MIC-values for Ag-Se NPs were 62.5 µg mL- 1, and the data clearly demonstrated that C. albicans was the organism that was most susceptible to the three types of NPs. The MIC value was 125 µg mL- 1 for both Ag NPs and Se NPs. In antibiofilm assay, 5 µg mL- 1 Ag-Se NPs inhibited C. albicans with a percentage of 90.88%, E. coli with a percentage of 90.70%, and S. aureus with a percentage of 90.62%. The synthesized NPs can be arranged as follows in decreasing order of antioxidant capacity as an antioxidant result: Ag-Se NPs > Se NPs > Ag NPs. The MB dye degradation in the presence of the synthesized Ag NPs, Se NPs, and bimetallic Ag-Se NPs was confirmed by the decrease in the measured absorbance (at 664 nm) after 20 min of exposure to sunlight. CONCLUSION: Our study provides insight towards the synthesis of bimetallic NPs through green methodologies, to develop synergistic combinatorial antimicrobials with possible applications in the treatment of infectious diseases caused by clinically and industrial relevant drug-resistant strains.

Myco-fabricated ZnO nanoparticles ameliorate neurotoxicity in mice model of Alzheimer's disease via acetylcholinesterase inhibition and oxidative stress reduction.

Alzheimer's disease (AD) is one of the primary health problems linked to the decrease of acetylcholine in cholinergic neurons and elevation in oxidative stress. Myco-fabrication of ZnO-NPs revealed excellent biological activities, including anti-inflammatory and acetylcholinesterase inhibitory potentials. This study aims to determine if two distinct doses of myco-fabricated ZnO-NPs have a positive impact on behavioral impairment and several biochemical markers associated with inflammation and oxidative stress in mice that have been treated by aluminum chloride (AlCl3) to induce AD. Sixty male mice were haphazardly separated into equally six groups. Group 1 was injected i.p. with 0.5 ml of deionized water daily during the experiment. Mice in group 2 received AlCl3 (50 mg/kg/day i.p.). Groups 3 and 4 were treated i.p. with 5 and 10 mg/kg/day of ZnO-NPs only, respectively. Groups 5 and 6 were given i.p. 5 and 10 mg/kg/day ZnO-NPs, respectively, add to 50 mg/kg/day AlCl3. Results showed that the AlCl3 caused an increase in the escape latency time and a reduction in the time spent in the target quadrant, indicating a decreased improvement in learning and memory. Moreover, acetylcholinesterase enzyme (AChE) activity and malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin 1ß (IL-1ß) levels were significantly increased, and the content of glutathione (GSH), activities of superoxide dismutase (SOD), catalase (CAT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), as well as levels of serotonin and dopamine, were decreased in brain tissues only in AlCl3 treated mice. However, treatment of mice with myco-fabrication of ZnO-NPs at doses of 5 or 10 mg/kg improves learning and memory function through ameliorate all the previous parameters in the AD mice group. The low dose of 5 mg/kg is more effective than a high dose of 10 mg/kg. In accordance with these findings, myco-fabricated ZnO-NPs could enhance memory and exhibit a protective influence against memory loss caused by AlCl3.

Bifunctional role of some biogenic nanoparticles in controlling wilt disease and promoting growth of common bean.

In the present era, nanomaterials are emerging as a powerful tool for management of plant disease and improving crop production to meet the growing global need for food. Thus, this paper was conducted to explore the effectiveness of five different types of nanoparticles (NPs) viz., Co3O4NPs, CuONPs, Fe3O4NPs, NiONPs, and ZnONPs as treatments for Fusarium wilt as well as their role in promoting growth of the common bean plant. The five types of NPs were applied as a treatment for wilt in two ways, therapeutic and protective plans under greenhouse conditions. In vivo experiments showed that all types of NPs significantly increased disease control and diminished the symptoms of Fusarium wilt for both incidence and severity. The recorded values for disease control using the respective NPs during the protective plan were 82.77, 60.17, 49.67, 38.23, and 70.59%. Meanwhile these values were 92.84, 64.67, 51.33, 45.61, 73.84% during the therapeutic plan. Moreover, CuONPs during the protective plan were the best among the five types of NPs employed in terms of wilt disease management. Regarding the use of these NPs as growth promoters, the obtained results confirmed the effectiveness of the five types of NPs in enhancing vegetative growth of the plant under greenhouse conditions, in comparison with control. Among the five NPs, CuONPs improved the plant vegetative growth and particularly increased the content of the photosynthetic pigments; chlorophyll-a (2.96 mg/g), -b (1.93 mg/g), and total carotenoids (1.16 mg/g). These findings suggest the successful and potential exploitation of nanomaterials in agriculture deployed as nano-based products including nano-fungicides and nano-fertilizers. In terms of sustainability, this promising and exceptional multifunctional role of these nanomaterials will surely exert positive impacts on both the environment and sustainable agriculture.

Gamma irradiation mediated production improvement of some myco-fabricated nanoparticles and exploring their wound healing, anti-inflammatory and acetylcholinesterase inhibitory potentials.

In the current scenario, scaling up the microbial production of nanoparticles with diverse biological applications is an emerging prospect for NPs' sustainable industry. Thus, this paper was conducted to develop a suitable applicative process for the myco-fabrication of cobalt-ferrite (CoFeNPs), selenium (SeNPs), and zinc oxide (ZnONPs) nanoparticles. A strain improvement program using gamma irradiation mutagenesis was applied to improve the NPs-producing ability of the fungal strains. The achieved yields of CoFeNPs, SeNPs, and ZnONPs were intensified by a 14.47, 7.85, and 22.25-fold increase from the initial yield following gamma irradiation and isolation of stable mutant strains. The myco-fabricated CoFeNPs, SeNPs, and ZnONPs were then exploited to study their wound healing, and anti-inflammatory. In addition, the acetylcholinesterase inhibition activities of the myco-fabricated NPs were evaluated and analyzed by molecular docking. The obtained results confirmed the promising wound healing, anti-inflammatory, and acetylcholinesterase inhibition potentials of the three types of NPs. Additionally, data from analyzing the interaction of NPs with acetylcholinesterase enzyme by molecular docking were in conformation with the experimental data.

Unlocking the biosynthetic potential of Penicillium roqueforti for hyperproduction of the immunosuppressant mycophenolic acid: Gamma radiation mutagenesis and response surface optimization of fermentation medium.

Based on the broad clinical utility of the immunosuppressant mycophenolic acid (MPA), this article aims to intensify the biosynthetic potential of Penicillium roqueforti for more effective hyperproduction of the drug. Several mutants were generated from irradiation mutagenesis and screened. Two strains (GM1013 and GM1093) presented an elevated MPA productivity with significant yield constancy over 10 subsequent generations. By investigating the effect of some phosphorous sources and mineral salts on MPA production by the two mutants, KH2 PO4 and FeSO4 ·7H2 O were most preferred by the two mutants for higher MPA production rates. Statistics-dependent experimental designs were also employed for optimizing medium components for maximum MPA production. Medium components were primarily screened using the Plackett-Burman model to demonstrate the most important components that most significantly affect MPA production. The concentrations of these significant components were then optimized through a central composite rotatable model. In conclusion, gamma-radiation mutation and response surface optimization resulted in a promising MPA productivity by P. roqueforti GM1013. To our knowledge, the MPA-yield achieved in this study (2933.32 mg L-1 ) is the highest reported by academic laboratories from P. roqueforti cultures, which could be of economic value for a prospective large industrialized application.

Effects of dietary supplementation of myco-fabricated zinc oxide nanoparticles on performance, histological changes, and tissues Zn concentration in broiler chicks.

A five weeks biological experiment was planned to investigate the impacts of dietary supplementation with zinc oxide nanoparticles (ZnONPs) synthesized by the endophytic fungus Alternaria tenuissima on productive performance, carcass traits, organ relative weights, serum biochemical parameters, histological alteration in some internal organs and concentration of this element in the serum, liver, thigh and breast muscle in broiler chicks. A total of 108 3-day-old commercial broiler chicks (Cobb 500) were individually weighed and equally distributed in a completely randomized design arrangement according to the dose of ZnONPs supplementation into 3 dietary experimental groups. There were 6 replications having 6 birds per replicate (n = 36/ treatment) for each treatment. The three experiential dietary treatments received corn-soybean meal-based diets enhanced with 0 (control), 40 and 60 mg/kg diet of ZnONPs respectively with feed and water were provided ad libitum consumption through 5 weeks life span. Present results indicated that after 5 weeks of feeding trial and as compared to control, the ZnONPs supplementation groups recorded higher body weight, improved feed consumption, feed conversion ratio and performance index. Serum biochemical analyses revealed that serum cholesterol, triglyceride, low density lipoprotein and uric acid decreased significantly, while high density lipoprotein and liver enzyme concentrations were increased significantly. Meanwhile, zinc accumulation in serum, liver and breast and thigh muscle were linearly increased with increasing zinc supplementation. It could be concluded that supplementation of ZnONPs to broiler diet at 40 or 60 mg/kg improved productive performance, birds' physiological status and the lower levels Zn (40 mg/kg diet) revealed promising results and can be used as an effective feed additive in broilers.

Bioprospecting endophytic fungi for antifeedants and larvicides and their enhancement by gamma irradiation.

The search and discovery of new natural products with antifeedant and larvicidal potentials to mitigate harmful insects are scientific pressing issues in the modern agriculture. In this paper, the antifeedant and larvicidal potentials of 69 fungal isolates were screened against the Egyptian cotton leafworm Spodoptera littoralis. A total of 17 isolates showed the insecticidal potentials with three promising isolates. These strains were Aspergillus sydowii, Lasiodiplodia theobromae, and Aspergillus flavus isolated from Ricinus communis (bark), Terminalia arjuna (Bark), and Psidium guajava (twigs), respectively. The effect of gamma irradiation on the antifeedant and larvicidal activities of the three strains was investigated. Exposure of the fungal spores to 1000 Gy of gamma rays significantly intensified both the antifeedant and larvicidal potentials. To identify compounds responsible for these activities, extracts of the three strains were fractionated by thin layer chromatography. The nature of the separated compounds namely, Penitrem A, 1, 3, 5, 8- tetramethyl- 4, 6-diethyl- 7- [2- (methoxycarbonyl)ethyl] porphyrin (from A. sydowii), Penitrem A, 2, 7, 12, 17-Tetramethyl-3, 5:8, 10:13, 15:18, 20-tetrakis (2,2-dimethylpropano) porphyrin (from A. flavus), N,N-Diethyl-3-nitrobenzamide, and Diisooctyl-phthalate (from L. theobromae) were studied by GC-MS analysis. These findings recommend endophytic fungi as promising sources of novel natural compounds to mitigate harmful insects.

Improving carboxymethyl cellulose edible coating using ZnO nanoparticles from irradiated Alternaria tenuissima.

In this paper, gamma-irradiation was successfully used to intensify the yield of Zinc oxide nanoparticles (ZnONPs) produced by the fungus Alternaria tenuissima as a sustainable and green process. The obtained data showed that 500 Gy of gamma-irradiation increased ZnONPs' yield to approximately four-fold. The synthesized ZnONPs were then exploited to develop active Carboxymethyl Cellulose films by casting method at two different concentration of ZnONPs 0.5% and 1.0%. The physicochemical, mechanical, antioxidant, and antimicrobial properties of the prepared films were evaluated. The incorporation of ZnONPs in the Carboxymethyl Cellulose films had significantly decreased solubility (from 78.31% to 66.04% and 59.72%), water vapor permeability (from 0.475 g m-2 to 0.093 g m-2 and 0.026 g m-2), and oxygen transfer rate (from 24.7 × 10-2 to 2.3 × 10-2 and 1.8 × 10-2) of the respective prepared films. Meanwhile, tensile strength (from 183.2 MPa to 203.34 MPa and 235.94 MPa), elongation (from 13.0% to 62.5% and 83.7%), and Yang's modulus (from 325.344 to 1410.0 and 1814.96 MPa) of these films were increased. Moreover, the antioxidant and antimicrobial activities against several human and plant pathogens the prepared of Carboxymethyl Cellulose-ZnONPs films were significantly increased. In conclusion, the prepared Carboxymethyl Cellulose-ZnONPs films showed enhanced activities in comparison with Carboxymethyl Cellulose film without NPs. With these advantages, the fabricated Carboxymethyl Cellulose-ZnONPs films in this study could be effectively utilized as protective edible coating films of food products.

A new endophyte Monascus ruber SRZ112 as an efficient production platform of natural pigments using agro-industrial wastes.

A number of biopigment applications in various industrial sectors are gaining importance due to the growing consumer interest in their natural origin. Thus, this work was conducted to valorize endophytic fungi as an efficient production platform for natural pigments. A promising strain isolated from leaves of Origanum majorana was identified as Monascus ruber SRZ112 produced several types of pigments. The nature of the pigments, mainly rubropunctamine, monascin, ankaflavin, rubropunctatin, and monascorubrin in the fungal extract was studied by LC/ESI-MS/MS analyses. As a first step towards developing an efficient production of red pigments, the suitability of seven types of agro-industrial waste was evaluated. The highest yield of red pigments was obtained using potato peel moistened with mineral salt broth as a culture medium. To increase yield of red pigments, favourable culture conditions including incubation temperature, incubation period, pH of moistening agent, inoculum concentration, substrate weight and moisture level were evaluated. Additionally, yield of red pigments was intensified after the exposure of M. ruber SRZ112 spores to 1.00 KGy gamma rays. The final yield was improved by a 22.12-fold increase from 23.55 to 3351.87 AU g-1. The anticancer and antioxidant properties of the pigment's extract from the fungal culture were also studied. The obtained data indicated activity of the extract against human breast cancer cell lines with no significant cytotoxicity against normal cell lines. The extract also showed a free radical scavenging potential. This is the first report, to our knowledge, on the isolation of the endophytic M. ruber SRZ112 strain with the successful production of natural pigments under solid-state fermentation using potato peel as a substrate.

Harnessing endophytic fungi for biosynthesis of selenium nanoparticles and exploring their bioactivities.

In the light of the fast growing several applications of selenium nanoparticles (SeNPs) in different industrial and agricultural sectors, this paper was conducted to explore the suitability of endophytic fungi as nano-factories for SeNPs. Thus, 75 fungal isolates were recovered from plant tissues and tested for their efficacy to biosynthesize SeNPs. Four promising strains were found able to synthesis SeNPs with different characteristics and identified. These strains were Aspergillus quadrilineatus isolated from the twigs of Ricinus communis, Aspergillus ochraceus isolated from the leaves of Ricinus communis, Aspergillus terreus isolated from the twigs of Azadirachta indica, and Fusarium equiseti isolated from the twigs of Hibiscus rose-sinensis. The synthesized SeNPs were characterized by several techniques viz., UV-Vis, X-ray diffraction, Dynamic light scattering analyses, High resolution transmission electron microscopy, and Fourier transform infrared spectroscopy, to study their crystalline structure, particle sized distribution, and morphology. Furthermore, the in vitro antimicrobial and antioxidant activities were evaluated. SeNPs synthesized by the four strains showed potent antifungal and antibacterial potentials against different human and phyto- pathogens. Moreover, SeNPs synthesized by the respective strains showed promising antioxidant power with IC50 values of 198.32, 151.23, 100.31, and 91.52 µg mL- 1. To the best of our knowledge, this is the first study on the use of endophytic fungi for SeNPs' biosynthesis. The presented research recommends the use of endophytic fungi as facile one-pot production bio-factories of SeNPs with promising characteristics.

Exploiting the exceptional biosynthetic potency of the endophytic Aspergillus terreus in enhancing production of Co3O4, CuO, Fe3O4, NiO, and ZnO nanoparticles using bioprocess optimization and gamma irradiation.

Developing a suitable applicative process and scaling up the microbial synthesis of nanomaterials is an attractive and emerging prospect for a future sustainable industrial production. In this paper, optimization of fermentation conditions for enhanced production of Co3O4, CuO, Fe3O4, NiO, and ZnO nanoparticles by the endophytic A. terreus ORG-1 was studied. Different cultivation conditions were evaluated. Then, a response surface methodology program was used to optimize physical conditions controlling the biosynthesis of these NPs. Finally, the use of gamma irradiation for improvement of NPs' production was adopted. Under the optimum conditions and after gamma irradiation, the final yields of the respective NPs reached 545.71, 651.67, 463.19, 954.88, 1356.42 mg L-1. To the best of our knowledge, this is the first report on the production and enhancement of different types of nanomaterials from one microbial culture that can open up the way towards the industrialization of the microbial production of nanomaterials.

Bioprospecting endophytic fungi for bioactive metabolites and use of irradiation to improve their bioactivities.

The search for new bioactive compounds with innovative modes of action and chemistry are desperately needed to tackle the increased emergence of drug-resistant microbes. With this view, this paper was conducted for the isolation, identification, and biological evaluation of fungal endophytes of eleven different plant species. A total of 69 endophytic strains were isolated and tested for the presence of bioactive metabolites with antifungal, antibacterial, anticancer, and antioxidant properties in their extracts. Upon screening, two promising strains were found to have all the before-mentioned activities. These strains were Aspergillus sydowii isolated from the bark of Ricinus communis and Aspergillus flavus isolated from the twigs of Psidium guajava. Major compounds present in extracts of the two strains were identified by GC-Mass analyses. Several well-known bioactive compounds as well as unreported ones were identified in the fungal extracts of the two strains. Furthermore, gamma irradiation (at 1000 Gy) of the fungal cultures resulted in improved bioactivities of extracts from the two strains. These findings recommend the two fungal strains as sources of antimicrobial, anticancer, and antioxidant compounds which may aid in the development of novel drugs. The presented research also explains the high-value of fungal endophytes as untapped sources of bioactive metabolites.

Use of mycorrhizal fungi and phosphorus fertilization to improve the yield of onion (Allium cepa L.) plant.

Improving the economical yield of commonly cultivated crops is one of the most pressing social and scientific issues in modern agriculture. This paper was conducted to investigate the bio-efficacy of arbuscular mycorrhizal fungi (AMF) in improving phosphorous (P) utilization and increasing the yield of onion plant grown in sandy soil under a drip irrigation system. The obtained results showed that AMF inoculation of onion and application of 120 kg P fertilizer ha-1 significantly increased the fresh and dry weights, chlorophyll content of onion as well as P concentration in the root, shoot, and bulb during two growing seasons. Moreover, AMF increased the bioavailability of P in the rhizosphere and significantly enhanced the N-utilization by the inoculated plant. The economic yield of the onion plant inoculated by AMF and fertilized by different doses of P fertilizer was much higher than that obtained by the control (without AMF). These findings indicated that inoculating the onion plant in the field with AMF could be very effective in increasing the yield of the onion plant. Additionally, this study suggests AMF as a low-cost and promising candidate for the sustainable production of the onion crop using reclaimed sandy soils and a drip irrigation system.

New and potent production platform of the acetylcholinesterase inhibitor huperzine A by gamma-irradiated Alternaria brassicae under solid-state fermentation.

Huperzine-A (HupA) is an emerging, powerful, and promising natural acetylcholinesterase inhibitor. Despite that, the achieved yields of HupA from microbial sources are still far from the industrial applications. Accordingly, this paper was conducted to valorize solid-state fermentation (SSF) as an efficient production platform of HupA. Four agro-industrial wastes, namely rice bran, potato peel, sugarcane bagasse, and wheat bran, were tested and screened as cultural substrates for the production of HupA by the endophytic Alternaria brassica under SSF. Maximum HupA production was attained on using rice bran moistened by Czapex's dox mineral broth. In the effort to increase the HupA titer, supplementation of the best moistening agent by different carbon and nitrogen sources was successfully investigated. Additionally, factors affecting HupA production under SSF including substrate concentration, moistening level, and inoculum concentration were optimized using response surface methodology. A Box-Behnken design was applied for generating a predictive model of the interactions between these factors. Under the optimum conditions of 15 g rice bran, inoculum concentration of 5 × 106 spores mL-1, and 60% moisture level, HupA concentration was intensified to 518.93 µg g-1. Besides, HupA production by the fungal strain was further enhanced using gamma-irradiation mutagenesis. The final HupA production was significantly intensified following exposure to 0.5 KGy gamma radiation to 1327 µg g-1, which represents a 12.85-fold increase. This is the first report on the successful production of the natural fungal metabolite HupA under SSF. Moreover, the achieved yield in this study using agro-industrial wastes may contribute to reducing the cost of HupA manufacture.Key points• Different agro-industrial by-products were tried as cultural substrates for the production of the acetylcholinesterase inhibitor HupA under SSF for the first time.• Factors affecting HupA production under SSF were optimized using response surface methodology.• The final HupA production was intensified following exposure to gamma radiation recording 1327 µg g-1, which represents a 12.85-fold increase.

Novel mycosynthesis of Co3O4, CuO, Fe3O4, NiO, and ZnO nanoparticles by the endophytic Aspergillus terreus and evaluation of their antioxidant and antimicrobial activities.

Several fungal endophytes were isolated and screened for their ability to biosynthesize a variety of nanoparticles (NPs), as a potentially simple and eco-friendly method with low cost. Among these fungi, a promising isolate named ORG-1 was found able to synthesize five different NPs types: Co3O4NPs, CuONPs, Fe3O4NPs, NiONPs, and ZnONPs. The ORG-1 strain was identified as Aspergillus terreus according to the morphological and molecular studies. Synthesis of these NPs was initially monitored by UV-Vis spectroscopy and further characterized by Fourier transform infrared spectroscopy. X-ray diffraction patterns revealed their crystalline structure. Dynamic light scattering analysis was applied to study the particle size distribution and stability. Transmission electron microscope studies indicated the morphology of the synthesized NPs. Additionally, the biological activities of the in vitro antioxidant and antimicrobial potentials were evaluated. Co3O4NPs, CuONPs, Fe3O4NPs, NiONPs, and ZnONPs showed promising antioxidant activity with 50% inhibitory concentrations of 85.44, 96.74, 102.41, 87.41, and 108.67 µg mL-1, respectively. The synthesized NPs exhibited potent antimicrobial activities against several plant and human pathogens. To our knowledge, this is the first report on the use of one microbial strain for the synthesis of a variety of NPs. This study suggests endophytic fungi as new and alternate platforms with an exceptional potentiality for the synthesis of NPs with promising activities. KEY POINTS: • Discovery of a promising endophytic fungus for synthesis of five different types of NPs. • Mycosynthesis and characterization of all the synthesized NPs were investigated. • The synthesized NPs showed promising antioxidant and antimicrobial activities.

Production of the anticancer drug taxol by the endophytic fungus Epicoccum nigrum TXB502: enhanced production by gamma irradiation mutagenesis and immobilization technique.

Taxol, a phyto-extracted diterpenoid, is the most commercially needed drug in cancer chemotherapy. In spite of the microbial production of taxol being successful and prospective, the reported yields are still not sufficient for large-scale production. Thus, the discovery of new taxol-producing microbial strains and production enhancement methodologies such as process optimization, strain improvement, and immobilization technique are the main objectives. In this paper, a taxol-producing start strain Epicoccum nigrum TXB502 (initial yield 61.35 µg L-1) was isolated from Taxus baccata and identified by morphological and molecular tools. The optimum cultivation and nutritional conditions were assessed by testing one parameter at a time approach that resulted in 88.59% significant production increase. In addition, a stable mutant with improved productivity (40.07% yield increase in comparison with the parent strain) was successfully developed after gamma irradiation mutagenesis of the start strain. The taxol titer was further improved via testing different immobilization carriers for both spores and mycelia of this mutant. Over taxol production was achieved using alginate-immobilized mycelia with the feasibility of conducting six successive production cycles in a semi-continuous form. The final total concentration reached 8187.77 µg taxol 6 L-1 which represents approximately 22-fold increase, as compared to the initial titer of the start strain. These findings can pave the way for the prospective industrial manufacturing of taxol, as the achieved taxol production in this study is the highest reported by academic laboratories for microbial cultures. KEY POINTS: • Discovery of a new taxol-producing endophytic fungus E. nigrum TXB502 strain. • Taxol yield was successfully improved via bioprocess optimization and strain mutagenesis. • Alginate-immobilized mycelia were efficient for a semi-continuous production of taxol. • The final total concentration of taxol showed approximately 22-fold increase as compared to the initial titer.

Microbial acetylcholinesterase inhibitors for Alzheimer's therapy: recent trends on extraction, detection, irradiation-assisted production improvement and nano-structured drug delivery.

Neurodegenerative disorders especially Alzheimer's disease (AD) are significantly threatening the public health. Acetylcholinesterase (AChE) inhibitors are compounds of great interest which can be used as effective agents for the symptomatic treatment of AD. Although plants are considered the largest source for these types of inhibitors, the microbial production of AChE inhibitors represents an efficient, easily manipulated, eco-friendly, cost-effective, and alternative approach. This review highlights the recent advances on the microbial production of AChE inhibitors and summarizes all the previously reported successful studies on isolation, screening, extraction, and detecting methodologies of AChE inhibitors from the microbial fermentation, from the earliest trials to the most promising anti-AD drug, huperzine A (HupA). In addition, improvement strategies for maximizing the industrial production of AChE inhibitors by microbes will be discussed. Finally, the promising applications of nano-material-based drug delivery systems for natural AChE inhibitor (HupA) will also be summarized. KEY POINTS: • AChE inhibitors are potential therapies for Alzheimer's disease. • Microorganisms as alternate sources for prospective production of such inhibitors. • Research advances on extraction, detection, and strategies for production improvement. • Nanotechnology-based approaches for an effective drug delivery for Alzheimer's disease.

Semi-continuous production of the anticancer drug taxol by Aspergillus fumigatus and Alternaria tenuissima immobilized in calcium alginate beads.

Taxol is the most profitable drug ever developed in cancer chemotherapy; however, the market demand for the drug greatly exceeds the supply that can be sustained from its natural sources. In this study, Aspergillus fumigatus TXD105-GM6 and Alternaria tenuissima TER995-GM3 were immobilized in calcium alginate beads and used for the production of taxol in shake flask cultures. In an effort to increase the taxol magnitude, immobilization conditions were optimized by response surface methodology program (RSM). The optimum levels of alginate concentration, calcium chloride concentration, and mycelium fresh weight were 5%, 4%, and 15% (w/v), respectively. Under these conditions, taxol production by the respective fungal strains was intensified to 901.94 µg L-1 and 529.01 µg L-1. Moreover, the immobilized mycelia of both strains were successfully used in the repeated production of taxol for six different fermentation cycles. The total taxol concentration obtained in all cycles reached 4540.14 µg L-1 by TXD105-GM6 and 2450.27 µg L-1 by TER995-GM3 strain, which represents 7.85- and 6.31-fold increase, as compared to their initial titers. This is the first report on the production of taxol in semi-continuous fermentation. To our knowledge, the taxol productivity achieved in this study is the highest reported by academic laboratories for microbial cultures which indicates the future possibility to reduce the cost of taxol production.

Solid-state fermentation for enhanced production of selenium nanoparticles by gamma-irradiated Monascus purpureus and their biological evaluation and photocatalytic activities.

Selenium nanoparticles (SeNPs) were successfully synthesized using the culture extract of Monascus purpureus ATCC16436 grown on sugarcane bagasse under solid-state fermentation. The rapid synthesis of SeNPs was completed after 30 min as confirmed by UV-Vis spectroscopy. Functional groups present in the synthesized SeNPs samples were confirmed by Fourier transform infrared spectroscopy. The synthesized SeNPs showed a single-phase crystalline structure. Transmission electron microscope revealed the spherical shape and the mean particle size was 46.58 nm. Dynamic light scattering analysis showed that the synthesized SeNPs were monodispersed and the recorded polydispersity index value was 0.205. Zeta potential value of - 24.01 mV indicated the high stability of SeNPs. Besides, the biological activities of antioxidant, anticancer and antimicrobial as well as the photocatalytic activities were also studied. SeNPs showed promising antioxidant activity with 50% inhibitory concentration of 85.92 µg mL-1. Based on the MTT assay, SeNPs inhibited the proliferation of normal human melanocytes, human breast and liver cancer cell lines with 50% inhibitory concentrations of 45.21, 61.86 and 200.15 µg mL-1, respectively. SeNPs showed broad spectrum of antimicrobial potential against the tested human and plant pathogens. SeNPs showed efficient degradation of methylene blue dye. Moreover, the effect of gamma irradiation on the production enhancement of SeNPs was also adopted. Exposure of the fungal spores to gamma rays at 1000 Gy increased the yield of SeNPs to approximately fivefold. Hence, this study suggests a new and alternate approach with the excellent biotechnological potentiality for the production of SeNPs.