A Structural In Silico Analysis of the Immunogenicity of L-Asparaginase from Penicillium cerradense.

L-asparaginase is an essential drug used to treat acute lymphoid leukemia (ALL), a cancer of high prevalence in children. Several adverse reactions associated with L-asparaginase have been observed, mainly caused by immunogenicity and allergenicity. Some strategies have been adopted, such as searching for new microorganisms that produce the enzyme and applying protein engineering. Therefore, this work aimed to elucidate the molecular structure and predict the immunogenic profile of L-asparaginase from Penicillium cerradense, recently revealed as a new fungus of the genus Penicillium and producer of the enzyme, as a motivation to search for alternatives to bacterial L-asparaginase. In the evolutionary relationship, L-asparaginase from P. cerradense closely matches Aspergillus species. Using in silico tools, we characterized the enzyme as a protein fragment of 378 amino acids (39 kDa), including a signal peptide containing 17 amino acids, and the isoelectric point at 5.13. The oligomeric state was predicted to be a homotetramer. Also, this L-asparaginase presented a similar immunogenicity response (T- and B-cell epitopes) compared to Escherichia coli and Dickeya chrysanthemi enzymes. These results suggest a potentially useful L-asparaginase, with insights that can drive strategies to improve enzyme production.

Comparative study on effect of pomegranate peel powder as natural preservative and chemical preservatives on quality and shelf life of muffins.

This research aims to investigate the potential of utilizing pomegranate peel powder (PPP) as a natural preservative in muffin preparation. Pomegranate peel is a rich source of bioactive compounds, including phenolics, flavonoids, and tannins, which possess high antioxidant and antimicrobial properties. The In-Vitro antifungal activity of pomegranate peel powder (8% PPP), potassium sorbate (0.1% PS) and calcium propionate (0.5% CP) was assessed against Penicillium sp. and Aspergillus sp. using poison food technique. The PPP showed the anti-fungal activity by delaying the growth of microorganism on media plate similar to the PS and CP. The effect of utilization of PPP on quality characteristics of muffins were compared with the muffins with chemical preservatives (0.1% PS and 0.5% CP). The viscosity and specific gravity of batter significantly increased from 7.98 to 11.87 Pa s and 1.089-1.398 respectively on addition of 8% PPP. The optical microscopic structure of PPP added batter revealed the decrease in the number of air cells from 24 to 12 with radius range of 6.42-72.72 µm and area range of 511.03-15,383.17 µm2. The functional properties of flour with PPP had higher water absorption capacity, foaming stability, emulsification activity and emulsion stability than others. The addition of PPP significantly increase the weight (32.83 g), and decrease the height (31.3 mm), volume (61.43 cm3), specific volume (1.67 cm3/g) and baking loss (10.19%). The 418.36% increase in fibre content, 14.46% and 18.46% decrease in carbohydrates and energy value was observed in muffin with 8% PPP as compared to control respectively. The total phenols was increased from 0.92 to 12.5 mg GAE/100 g, total tannin from 0.2 to 8.27 mg GAE/100 g, In-vitro antioxidant activity by DPPH from 6.97 to 29.34% and In-vitro antioxidant activity by FRAP from 0.497 to 2.934 mg AAE/100 g in muffins added with 8% PPP. The muffin with PPP was softer than control and muffin with 0.1% PS. The addition of PPP resulted to improve in muffin texture but taste slightly bitter. During the storage of muffins at room temperature (27-30 °C), the moisture content of muffin with PPP was reduced from 17.04 to 13.23% which was higher than the rest of the treatments. Similarly, the hardness of sample with PPP was higher than the sample with 0.5% CP, but lowers than control and sample with 0.1% PS throughout the storage period. The results suggest that pomegranate peel powder can be successfully used as a natural preservative in place of chemical preservatives in muffins, to extend the shelf life. This study provides the opportunity to use PPP as functional ingredient and natural preservative in different bakery products.

A New Quinazolinone Alkaloid along with Known Compounds with Seed-Germination-Promoting Activity from Rhodiola tibetica Endophytic Fungus Penicillium sp. HJT-A-6.

A new quinazolinone alkaloid named peniquinazolinone A (1), as well as eleven known compounds, 2-(2-hydroxy-3-phenylpropionamido)-N-methylbenzamide (2), viridicatin (3), viridicatol (4), (±)-cyclopeptin (5a/5b), dehydrocyclopeptin (6), cyclopenin (7), cyclopenol (8), methyl-indole-3-carboxylate (9), 2,5-dihydroxyphenyl acetate (10), methyl m-hydroxyphenylacetate (11), and conidiogenone B (12), were isolated from the endophytic Penicillium sp. HJT-A-6. The chemical structures of all the compounds were elucidated by comprehensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS. The absolute configuration at C-13 of peniquinazolinone A (1) was established by applying the modified Mosher's method. Compounds 2, 3, and 7 exhibited an optimal promoting effect on the seed germination of Rhodiola tibetica at a concentration of 0.01 mg/mL, while the optimal concentration for compounds 4 and 9 to promote Rhodiola tibetica seed germination was 0.001 mg/mL. Compound 12 showed optimal seed-germination-promoting activity at a concentration of 0.1 mg/mL. Compared with the positive drug 6-benzyladenine (6-BA), compounds 2, 3, 4, 7, 9, and 12 could extend the seed germination period of Rhodiola tibetica up to the 11th day.

Design, Synthesis, Bioactive Evaluation, and Molecular Dynamics Simulation of Novel 4H-Pyrano[3,2-c]pyridine Analogues as Potential Sterol 14α-Demethylase (CYP51) Inhibitors.

To discover potential sterol 14α-demethylase (CYP51) inhibitors, thirty-four unreported 4H-pyrano[3,2-c]pyridine derivatives were designed and synthesized. The assay results indicated that most compounds displayed significant fungicidal activity against Sclerotinia sclerotiorum, Colletotrichum lagenarium, Botrytis cinerea, Penicillium digitatum, and Fusarium oxysporum at 16 µg/mL. The half maximal effective concentration (EC50) values of compounds 7a, 7b, and 7f against B. cinerea were 0.326, 0.530, and 0.610, respectively. Namely, they had better antifungal activity than epoxiconazole (EC50 = 0.670 µg/mL). Meanwhile, their half maximal inhibitory concentration (IC50) values against CYP51 were 0.377, 0.611, and 0.748 µg/mL, respectively, representing that they also possessed better inhibitory activities than epoxiconazole (IC50 = 0.802 µg/mL). The fluorescent quenching tests of proteins showed that 7a and 7b had similar quenching patterns to epoxiconazole. The molecular dynamics simulations indicated that the binding free energy of 7a and epoxiconazole to CYP51 was -35.4 and -27.6 kcal/mol, respectively.

An at-leg pellet and associated Penicillium sp. provide multiple protections to mealybugs.

Beneficial fungi are well known for their contribution to insects' adaptation to diverse habitats. However, where insect-associated fungi reside and the underlying mechanisms of insect-fungi interaction are not well understood. Here, we show a pellet-like structure on the legs of mealybugs, a group of economically important insect pests. This at-leg pellet, formed by mealybugs feeding on tomato but not by those on cotton, potato, or eggplant, originates jointly from host secretions and mealybug waxy filaments. A fungal strain, Penicillium citrinum, is present in the pellets and it colonizes honeydew. P. citrinum can inhibit mealybug fungal pathogens and is highly competitive in honeydew. Compounds within the pellets also have inhibitory activity against mealybug pathogens. Further bioassays suggest that at-leg pellets can improve the survival rate of Phenacoccus solenopsis under pathogen pressure, increase their sucking frequency, and decrease the defense response of host plants. Our study presents evidences on how a fungi-associated at-leg pellet provides multiple protections for mealybugs through suppressing pathogens and host defense, providing new insights into complex insect × fungi × plant interactions and their coevolution.

Antagonistic Activities of Metschnikowia pulcherrima Isolates Against Penicillium expansum on Amasya Apples.

Postharvest fungal diseases cause serious fruit losses and food safety issues worldwide. The trend in preventing food loss and waste has shifted to environmentally friendly and sustainable methods, such as biological control. Penicillium expansum is a common postharvest contaminant fungus that causes blue mould disease and patulin formation on apples. This study aimed to provide biocontrol using Metschnikowia pulcherrima isolates against P. expansum, and to understand their antagonistic action mechanisms. In vitro, 38.77-51.69% of mycelial growth inhibition of P. expansum was achieved by M. pulcherrima isolates with the dual culture assay, while this rate was 69.45-84.89% in the disc diffusion assay. The disease symptoms of P. expansum on wounds were reduced by M. pulcherrima, on Amasya apples. The lesion diameter, 41.84 mm after 12 d of incubation in control, was measured as 24.14 mm when treated with the most effective M. pulcherrima DN-MP in vivo. Although the antagonistic mechanisms of M. pulcherrima isolates were similar, there was a difference between their activities. In general, DN-HS and DN-MP isolates were found to be more effective. In light of all these results, it can be said that M. pulcherrima isolates used in the study have an antagonistic effect against the growth of P. expansum both in vitro and in vivo in Amasya apples, therefore, when the appropriate formulation is provided, they can be used as an alternative biocontrol agent to chemical fungicides in the prevention of postharvest diseases.

Penifuranone A: A Novel Alkaloid from the Mangrove Endophytic Fungus Penicillium crustosum SCNU-F0006.

One previously undescribed alkaloid, named penifuranone A (1), and three known compounds (2-4) were isolated from the mangrove endophytic fungus Penicillium crustosum SCNU-F0006. The structure of the new alkaloid (1) was elucidated based on extensive spectroscopic data analysis and single-crystal X-ray diffraction analysis. Four natural isolates and one new synthetic derivative of penifuranone A, compound 1a, were screened for their antimicrobial, antioxidant, and anti-inflammatory activities. Bioassays revealed that penifuranone A (1) exhibited strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 42.2 µM. The docking study revealed that compound 1 exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds.

Novel Bioactive Natural Products from Marine-Derived Penicillium Fungi: A Review (2021-2023).

Marine-derived Penicillium fungi are productive sources of structurally unique and diverse bioactive secondary metabolites, representing a hot topic in natural product research. This review describes structural diversity, bioactivities and statistical research of 452 new natural products from marine-derived Penicillium fungi covering 2021 to 2023. Sediments are the main sources of marine-derived Penicillium fungi for producing nearly 56% new natural products. Polyketides, alkaloids, and terpenoids displayed diverse biological activities and are the major contributors to antibacterial activity, cytotoxicity, anti-inflammatory and enzyme inhibitory capacities. Polyketides had higher proportions of new bioactive compounds in new compounds than other chemical classes. The characteristics of studies in recent years are presented.

Antifungal Activities of Biogenic Silver Nanoparticles Mediated by Marine Algae: In Vitro and In Vivo Insights of Coating Tomato Fruit to Protect against Penicillium italicum Blue Mold.

In an attempt to reduce such decay induced by pathogenic causes, several studies investigated the effectiveness of nanoparticles (NPs) that play a vital role in saving food products, especially fruits. Current research delves into biogenic silver nanoparticles (using marine alga Turbinaria turbinata (Tt/Ag-NPs) and their characterization using FT-IR, TEM, EDS, and zeta potential. Some pathogenic fungi, which cause fruit spoilage, were isolated. We studied the impact of using Tt/Ag-NPs to protect against isolated fungi in vitro, and the influence of Tt/Ag-NPs as a coating of tomato fruit to protect against blue mold caused by Penicillium italicum (OR770486) over 17 days of storage time. Five treatments were examined: T1, healthy fruits were used as the positive control; T2, healthy fruits sprayed with Tt/Ag-NPs; T3, fruits infected with P. italicum followed by coating with Tt/Ag-NPs (pre-coating); T4, fruits coated with Tt/Ag-NPs followed by infection by P. italicum (post-coating); and T5, the negative control, fruits infected by P. italicum. The results displayed that Tt/Ag-NPs are crystalline, spherical in shape, with size ranges between 14.5 and 39.85 nm, and negative charges. Different concentrations of Tt/Ag-NPs possessed antifungal activities against Botrytis cinerea, Rhodotorula mucilaginosa, Penicillium expansum, Alternaria alternate, and Stemphylium vesicarium. After two days of tomatoes being infected with P. italicum, 55% of the fruits were spoilage. The tomato fruit coated with Tt/Ag-NPs delayed weight loss, increased titratable acidity (TA%), antioxidant%, and polyphenol contents, and decreased pH and total soluble solids (TSSs). There were no significant results between pre-coating and post-coating except in phenol contents increased in pre-coating. A particular focus is placed on the novel and promising approach of utilizing nanoparticles to combat foodborne pathogens and preserve commodities, with a spotlight on the application of nanoparticles in safeguarding tomatoes from decay.

Enhancing biological control of postharvest green mold in lemons: Synergistic efficacy of native yeasts with diverse mechanisms of action.

Argentina is among the most important lemon fruit producers in the world. Penicillium digitatum is the primary lemon fungal phytopathogen, causing green mold during the postharvest. Several alternatives to the use of synthetic fungicides have been developed, being the use of biocontrol yeasts one of the most promising. Although many of the reports are based on the use of a single yeast species, it has been shown that the combination of agents with different mechanisms of action can increase control efficiency through synergistic effects. The combined use of native yeasts with different mechanisms of action had not been studied as a biological control strategy in lemons. In this work, the mechanisms of action of native yeasts (Clavispora lusitaniae AgL21, Clavispora lusitaniae AgL2 and Clavispora lusitaniae AcL2) with biocontrol activity against P. digitatum were evaluated. Isolate AgL21 was selected for its ability to form biofilm, colonize lemon wounds, and inhibit fungal spore germination. The compatibility of C. lusitaniae AgL21 with two killer yeasts of the species Kazachstania exigua (AcL4 and AcL8) was evaluated. In vivo assays were then carried out with the yeasts applied individually or mixed in equal cell concentrations. AgL21 alone was able to control green mold with 87.5% efficiency, while individual killer yeasts were significantly less efficient (43.3% and 38.3%, respectively). Inhibitory effects were increased when C. lusitaniae AgL21 and K. exigua strains were jointly applied. The most efficient treatment was the combination of AgL21 and AcL4, reaching 100% efficiency in wound protection. The combination of AgL21 with AcL8 was as well promising, with an efficiency of 97.5%. The combined application of native yeasts showed a synergistic effect considering that the multiple mechanisms of action involved could hinder the development of green mold in lemon more efficiently than using single yeasts. Therefore, this work demonstrates that the integration of native yeasts with diverse modes of action can provide new insights to formulate effective microbial consortia. This could lead to the development of tailor-made biofungicides, allowing control of postharvest fungal diseases in lemons while remaining competitive with traditionally used synthetic chemicals.

Penicillium oxalicum induced phosphate precipitation enhanced cadmium (Cd) immobilization by simultaneously accelerating Cd biosorption and biomineralization.

Soil cadmium (Cd) is immobilized by the progressing biomineralization process as microbial induced phosphate precipitation (MIPP), which is regulated by phosphate (P) solubilizing microorganisms and P sources. However, little attention has been paid to the implications of Cd biosorption during MIPP. In this study, the newly isolated Penicillium oxalicum could immobilize 5.4-12.6 % of Cd2+, while the presence of hydroxyapatite (HAP) considerably enhanced Cd2+ immobilization in P. oxalicum and reached over 99 % Cd2+ immobilization efficiency within 7 days. Compared to P. oxalicum mono inoculation, MIPP dramatically boosted Cd biosorption and biomineralization efficiency by 71 % and 16 % after 96 h cultivation, respectively. P. oxalicum preferred to absorbing Cd2+ and reaching maximum Cd2+ biosorption efficiency of 87.8 % in the presence of HAP. More surface groups in P. oxalicum and HAP mineral involved adsorption which resulted in the formation of Cd-apatite [Ca8Cd2(PO4)6(OH)2] via ion exchange. Intracellular S2-, secreted organic acids and soluble P via HAP solubilization complexed with Cd2+, progressively mineralized into Cd5(PO4)3OH, Cd(H2PO4)2, C4H6CdO4 and CdS. These results suggested that Cd2+ immobilization was enhanced simultaneously by the accelerated biosorption and biomineralization during P. oxalicum induced P precipitation. Our findings revealed new mechanisms of Cd immobilization in MIPP process and offered clues for remediation practices at metal contaminated sites.

Comparative physiological and transcriptomic analysis reveals an improved biological control efficacy of Sporidiobolus pararoseus Y16 enhanced with ascorbic acid against the oxidative stress tolerance caused by Penicillium expansum in pears.

Sporidiobolus pararoseus Y16, a species of significant ecological importance, has distinctive physiological and biological regulatory systems that aid in its survival and environmental adaptation. The goal of this investigation was to understand the complex interactions between physiological and molecular mechanisms in pear fruits as induced by S. pararoseus Y16. The study investigated the use of S. pararoseus Y16 and ascorbic acid (VC) in combination in controlling blue mold decay in pears via physiological and transcriptomic approach. The study results showed that treatment of S. pararoseus Y16 with 150 µg/mL VC reduced pears blue mold disease incidence from 43% to 11%. Furthermore, the combination of S. pararoseus Y16 and VC significantly inhibited mycelia growth and spore germination of Penicillium expansum in the pear's wounds. The pre-treatment did not impair post-harvest qualities of pear fruit but increased antioxidant enzyme activity specifically polyphenol oxidase (PPO), peroxidase (POD), catalase (CAT) activities as well as phenylalanine ammonia-lyase (PAL) enzyme activity. The transcriptome analysis further uncovered 395 differentially expressed genes (DEGs) and pathways involved in defense mechanisms and disease resistance. Notable pathways of the DEGs include plant-pathogen interaction, tyrosine metabolism, and hormone signal transduction pathways. The integrative approach with both physiological and transcriptomic tools to investigate postharvest pathology in pear fruits with clarification on how S. pararoseus Y16 enhanced with VC, improved gene expression for disease defense, and create alternative controls strategies for managing postharvest diseases.

Genome Mining of a Deep-Sea-Derived Penicillium allii-sativi Revealed Polyketide-Terpenoid Hybrids with Antiosteoporosis Activity.

Two novel meroterpenoids, alliisativins A and B (1, 2) were discovered through a genome-based exploration of the biosynthetic gene clusters of the deep-sea-derived fungus Penicillium allii-sativi MCCC entry 3A00580. Extensive spectroscopic analysis, quantum calculations, chemical derivatization, and biogenetic considerations were utilized to establish their structures. Alliisativins A and B (1, 2) possess a unique carbon skeleton featuring a drimane sesquiterpene with a highly oxidized polyketide. Noteworthily, alliisativin A (1) showed dual activity in promoting osteogenesis and inhibiting osteoclast, indicating an antiosteoporosis potential.

Lipolytic production from solid-state fermentation of the filamentous fungus Penicillium polonicum and its applicability as biocatalyst in the synthesis of ethyl oleate.

Lipases represent versatile biocatalysts extensively employed in transesterification reactions for ester production. Ethyl oleate holds significance in biodiesel production, serving as a sustainable alternative to petroleum-derived diesel. In this study, our goal was to prospect lipase and assess its efficacy as a biocatalyst for ethyl oleate synthesis. For quantitative analysis, a base medium supplemented with Rhodamine B, olive oil, and Tween 80 was used. Solid-state fermentation utilized crambe seeds of varying particle sizes and humidity levels as substrates. In the synthesis of ethyl oleate, molar ratios of 1:3, 1:6, and 1:9, along with a total enzymatic activity of 60 U in n-heptane, were utilized at temperatures of 30 °C, 37 °C, and 44 °C. Reactions were conducted in a shaker at 200 rpm for 60 min. As a result, we first identified Penicillium polonicum and employed the method of solid-state fermentation using crambe seeds as a substrate to produce lipase. Our findings revealed heightened lipolytic activity (22.5 Ug-1) after 96 h of fermentation using crambe cake as the substrate. Optimal results were achieved with crambe seeds at a granulometry of 0.6 mm and a fermentation medium humidity of 60%. Additionally, electron microscopy suggested the immobilization of lipase in the substrate, enabling enzyme reuse for up to 4 cycles with 100% enzymatic activity. Subsequently, we conducted applicability tests of biocatalysts for ethyl oleate synthesis, optimizing parameters such as the acid/alcohol molar ratio, temperature, and reaction time. We attained 100% conversion within 30 min at 37 °C, and our results indicated that the molar ratio proportion did not significantly influence the outcome. These findings provide a methodological alternative for the utilization of biocatalysts in ethyl oleate synthesis.

Lipid-Lowering Meroterpenoids Penihemeroterpenoids A-F from Penicillium herquei GZU-31-6 via Targeting the AMPK/ACC/SREBP-1c Signaling Pathway.

Penihemeroterpenoids A-C, the first meroterpenoids with an unprecedented 6/5/6/5/5/6/5 heptacyclic ring system, together with precursors penihemeroterpenoids D-F, were co-isolated from the fungus Penicillium herquei GZU-31-6. Among them, penihemeroterpenoids C-F exhibited lipid-lowering effects comparable to those of the positive control simvastatin by the activation of the AMPK/ACC/SREBP-1c signaling pathway, downregulated the mRNA levels of lipid synthesis genes FAS and PNPLA3, and increased the level of mRNA expression of the lipid export gene MTTP.

Antifungal efficiency and mechanisms of ethyl ferulate against postharvest pathogens.

Postharvest loss caused by a range of pathogens necessitates exploring novel antifungal compounds that are safe and efficient in managing the pathogens. This study evaluated the antifungal activity of ethyl ferulate (EF) and explored its mechanisms of action against Alternaria alternata, Aspergillus niger, Botrytis cinerea, Penicillium expansum, Penicillium digitatum, Geotrichum candidum and evaluated its potential to inhibit postharvest decay. The results demonstrated that EF exerts potent antifungal activity against a wide board of postharvest pathogens. Results also revealed that its antifungal mechanism is multifaceted: EF may be involved in binding to and disturbing the integrity of the fungal plasma membrane, causing leakage of intracellular content and losing normal morphology and ultrastructure. EF also induced oxidative stress in the pathogen, causing membrane lipid peroxidation and malondialdehyde accumulation. EF inhibited the critical gene expression of the pathogen, affecting its metabolic regulation, antioxidant metabolism, and cell wall degrading enzymes. EF exhibited antifungal inhibitory activity when applied directly into peel wounds or after incorporation with chitosan coating. Due to its wide board and efficient antifungal activity, EF has the potential to provide a promising alternative to manage postharvest decay.

Peniditerpenoids A and B: Oxidized Indole Diterpenoids with Osteoclast Differentiation Inhibitory Activity from a Mangrove-Sediment-Derived Penicillium sp.

An unprecedented di-seco-indole diterpenoid, peniditerpenoid A (1), and a rare N-oxide-containing indole diterpenoid derivative, peniditerpenoid B (2), together with three known ones (3-5), were obtained from the mangrove-sediment-derived fungus Penicillium sp. SCSIO 41411. Their structures were determined by the analysis of spectroscopic data, quantum chemical calculations, and X-ray diffraction analyses. Peniditerpenoid A (1) inhibited lipopolysaccharide-induced NF-κB with an IC50 value of 11 µM and further effectively prevented RANKL-induced osteoclast differentiation in bone marrow macrophages. In vitro studies demonstrated that 1 exerted significant inhibition of NF-κB activation in the classical pathway by preventing TAK1 activation, IκBα phosphorylation, and p65 translocation. Furthermore, 1 effectively reduced the level of NFATc1 activation, resulting in the attenuation of osteoclast differentiation. Our findings suggest that 1 holds promise as an inhibitor with significant potential for the treatment of diseases related to osteoporosis.

Histone H2B lysine 122 and lysine 130, as the putative targets of Penicillium oxalicum LaeA, play important roles in asexual development, expression of secondary metabolite gene clusters, and extracellular glycoside hydrolase synthesis.

Core histones in the nucleosome are subject to a wide variety of posttranslational modifications (PTMs), such as methylation, phosphorylation, ubiquitylation, and acetylation, all of which are crucial in shaping the structure of the chromatin and the expression of the target genes. A putative histone methyltransferase LaeA/Lae1, which is conserved in numerous filamentous fungi, functions as a global regulator of fungal growth, virulence, secondary metabolite formation, and the production of extracellular glycoside hydrolases (GHs). LaeA's direct histone targets, however, were not yet recognized. Previous research has shown that LaeA interacts with core histone H2B. Using S-adenosyl-L-methionine (SAM) as a methyl group donor and recombinant human histone H2B as the substrate, it was found that Penicillium oxalicum LaeA can transfer the methyl groups to the C-terminal lysine (K) 108 and K116 residues in vitro. The H2BK108 and H2BK116 sites on recombinant histone correspond to P. oxalicum H2BK122 and H2BK130, respectively. H2BK122A and H2BK130A, two mutants with histone H2B K122 or K130 mutation to alanine (A), were constructed in P. oxalicum. The mutants H2BK122A and H2BK130A demonstrated altered asexual development and decreased extracellular GH production, consistent with the findings of the laeA gene deletion strain (ΔlaeA). The transcriptome data showed that when compared to wild-type (WT) of P. oxalicum, 38 of the 47 differentially expressed (fold change ≥ 2, FDR ≤ 0.05) genes that encode extracellular GHs showed the same expression pattern in the three mutants ΔlaeA, H2BK122A, and H2BK130A. The four secondary metabolic gene clusters that considerably decreased expression in ΔlaeA also significantly decreased in H2BK122A or H2BK130A. The chromatin of promotor regions of the key cellulolytic genes cel7A/cbh1 and cel7B/eg1 compacted in the ΔlaeA, H2BK122A, and H2BK130A mutants, according to the results of chromatin accessibility real-time PCR (CHART-PCR). The chromatin accessibility index dropped. The histone binding pocket of the LaeA-methyltransf_23 domain is compatible with particular histone H2B peptides, providing appropriate electrostatic and steric compatibility to stabilize these peptides, according to molecular docking. The findings of the study demonstrate that H2BK122 and H2BK130, which are histone targets of P. oxalicum LaeA in vitro, are crucial for fungal conidiation, the expression of gene clusters encoding secondary metabolites, and the production of extracellular GHs.

Comprehensive Analysis of Penicillium Sclerotiorum: Biology, Secondary Metabolites, and Bioactive Compound Potential─A Review.

The filamentous fungus Penicillium sclerotiorum is significant in ecological and industrial domains due to its vast supply of secondary metabolites that have a diverse array of biological functions. We have gathered the metabolic potential and biological activities associated with P. sclerotiorum metabolites of various structures, based on extensive research of the latest literature. The review incorporated literature spanning from 2000 to 2023, drawing from reputable databases including Google Scholar, ScienceDirect, Scopus, and PubMed, among others. Ranging from azaphilones, meroterpenoids, polyketides, and peptides group exhibits fascinating potential pharmacological activities such as antimicrobial, anti-inflammatory, and antitumor effects, holding promise in pharmaceutical and industrial sectors. Additionally, P. sclerotiorum showcases biotechnological potential through the production of enzymes like ß-xylosidases, ß-d-glucosidase, and xylanases, pivotal in various industrial processes. This review underscores the need for further exploration into its genetic foundations and cultivation conditions to optimize the yield of valuable compounds and enzymes, highlighting the unexplored potential of P. sclerotiorum in diverse applications across industries.

Purification of andibenin and a chromanone analogue from rhizospheric Aspergillus flavus and soil-borne Penicillium notatum exhibiting cytotoxic and antibacterial properties.

The discovery of bioactive compounds from fungal natural sources holds immense potential for the development of novel therapeutics. The present study investigates the extracts of soil-borne Penicillium notatum and rhizosphere-inhabiting Aspergillus flavus for their antibacterial, antifungal, and cytotoxic potential. Additionally, two compounds were purified using chromatographic and spectroscopic techniques. The results demonstrated that the ethyl acetate fraction of A. flavus exhibited prominent cytotoxic activity against Artemia salina, whereas the ethyl acetate fraction of P. notatum displayed promising antibacterial potential. At dose concentrations of 10, 100, and 1000 µg mL-1, the ethyl acetate fraction of A. flavus showed mortality percentages of 7.6%, 66.4%, and 90%, respectively. The ethyl acetate fraction of P. notatum extract exhibited significant antibacterial activity, forming inhibition zones measuring 41, 38, 34, 34, and 30 mm against B. subtilis, S. flexneri, E. coli, K. pneumoniae, and S. aureus, respectively, at 1000 µg mL-1. At this concentration, inhibition zones of 28, 27, and 15 mm were recorded for P. vulgaris, S. typhi, and X. oryzae. Using bioassay-guided approach, one compound each was purified from the fungal extracts. The initial purification involved mass spectroscopic analysis, followed by structural elucidation using 500 MHz nuclear magnetic resonance (NMR) spectroscopy. Compound 1, derived from A. flavus, was identified as ethyl 2-hydroxy-5,6-dimethyl-4-oxocyclohex-2-ene-1-carboxylate, with a mass of 212, whereas compound 2, isolated from P. notatum, was identified as 3-amino-2-(cyclopenta-2,4-dien-1-ylamino)-8-methoxy-4H-chromen-4-one, with an exact mass of 270. Based on bioassay results, compound 1 was subjected to brine shrimp lethality assay and compound 2 was tested for its antibacterial potential. Compound 1 exhibited 30% lethality against brine shrimp larvae at a concentration of 100 µg mL-1, whereas at 1000 µg mL-1 the mortality increased to 70%. Compound 2 displayed notable antibacterial potential, forming inhibition zones of 30, 24, 19, and 12 mm against S. aureus, E. coli, B. subtilis, and S. flexneri, respectively. In comparison, the standard antibiotic tetracycline produced inhibition zones of 18, 18, 15, and 10 mm against the respective bacterial strains at the same concentration.