Butyrolactones from the fungus Aspergillus terreus BCC 4651

Two new butenolides, butyrolactones VI (1) and VII (2), were isolated together with six known compounds, butyrolactones I (3), II (4), IV (5), and V (6), aspernolide B (7), and bisdethiodi(methylthio)acetylaranotin (8) from the fungus Aspergillus terreus BCC 4651. Compound 8, exhibiting a minimum inhibitory concentration (MIC) value of 1.56 μg/ml against Mycobacterium tuberculosis H37Ra, proved to be the antimycobacterial principle from the culture of this fungus. On the other hand, butyrolactone V (6) showed antiplasmodial activity against Plasmodium falciparum K1 with an IC?? of 7.9 μg/ml.     

(+)‐Geodin from Aspergillus terreus

The fungal metabolite (+)‐geodin [systematic name: (2R)‐methyl 5,7‐dichloro‐4‐hydroxy‐6′‐methoxy‐6‐methyl‐3,4′‐dioxospiro[benzofuran‐2,1′‐cyclohexa‐2′,5′‐diene]‐2′‐carboxylate], C₁₇H₁₂Cl₂O₇, was isolated from Aspergillus terreus. The crystal structure contains two independent molecules in the asymmetric unit. Molecules denoted 1 interact through O—H...O hydrogen bonds creating chains of molecules parallel to the crystallographic 2₁ screw axis. Molecules denoted 2 interact through an O...Cl halogen bond, also creating chains of molecules parallel to the crystallographic 2₁ screw axis. Molecules 1 and 2 interact through another O...Cl halogen bond. The two molecules are similar but molecules 2 have a slightly more planar cyclohexadiene ring than molecules 1. The absolute structure of (+)‐geodin has been unequivocally assigned with the spiro centre having the R configuration in both molecules. The structurally related (+)‐griseofulvin has an S configuration at the spiro centre, a difference of potential biological and biosynthetic relevance.     

Terretonin O: a new meroterpenoid from Aspergillus terreus

Abstract

Terretonin O (1), a new meroterpenoid, was isolated individually from both methanolic extracts of thermophilic Aspergillus terreus TM8 and marine Aspergillus terreus LGO13. The recently reported terretonins M (2) and N (3) were further isolated from the fungus LGO13 along with nine known compounds, terrelumamide A (4), terrein (5), methyl-3,4,5-trimethoxyl-2-[2-(nicotinamide)benzamido] benzoate (6), butyrolactones I-III (7–9), aspulvinone O (10), ergosterol, ergost-4-ene-3-one and methyl linoleate. Structure of terretonin O (1) was established on the bases of HRESIMS, 1D and 2D NMR spectra and comparison with its analogues in literatures. The relative stereochemistry of 1 was assigned on the basis of NOESY spectra and comparison with reported configuration of its congener compounds 2 and 3. The antimicrobial and cytotoxic activities of the fungal extracts and obtained compounds were assayed using a set of microorganisms, and cervix carcinoma cell line (KB-3-1), respectively. Isolation and taxonomical characterization of the producing strains are reported.     

A new lumazine peptide penilumamide E from the fungus Aspergillus terreus

A new rare lumazine peptide, penilumamide E (1), together with 13 known compounds (2–14) were isolated from the fungus Aspergillus terreus. Their structures were identified by spectroscopic techniques. The relative configuration of 1 was confirmed by single-crystal X-ray diffraction analysis. Compound 10 exhibited antimalarial activity against Plasmodium falciparum with IC₅₀ values of 2.83 μg/mL. Compounds 4 and 6 showed weak cytotoxicity against cholangiocarcinoma (CCA) cell lines. In addition, 4 and 11 exhibited weak cytotoxicity against human hepatoma cell line.     

Terretonin D1, a new meroterpenoid from marine-derived Aspergillus terreus ML-44

A new meroterpenoid, named terretonin D1 (1), and three known ones, terretonin (2), terretonin A (3), and terretonin D (4), were isolated from marine-derived fungus Aspergillus terreus ML-44. The structure of 1 was elucidated by extensive spectroscopic methods, including 1D and 2D NMR, HR-ESI-MS, and the absolute configuration was determined by X-ray crystallographic analysis. The anti-inflammation activity of 1–4 was preliminarily tested, and all of them weakly inhibited the nitric oxide (NO) production of RAW264.7 macrophages stimulated by lipopolysaccharide (LPS), with inhibitory rates of 22–34% at 50?μg/mL.     

Terrenolide S,a new antileishmanial butenolide from the endophytic fungus Aspergillus terreus

Terrenolide S, a new butenolide derivative (6), together with six known compounds: (22E,24R)-stigmasta-5,7,22-trien-3-β-ol (1), stigmast-4-ene-3-one (2), stigmasta-4,6,8(14),22-tetraen-3-one (3), terretonin A (4), terretonin (5) and butyrolactone VI (7) have been isolated from the endophytic fungus Aspergillus terreus isolated from the roots of Carthamus lanatus (Asteraceae). Their structures were established by extensive spectroscopic analyses (1D, 2D NMR and HRESIMS), as well as optical rotation measurement and comparison with literature data. Compound 1 displayed a potent activity towards methicillin-resistant Staphylococcus aureus (MRSA) and Cryptococcus neoformans with IC₅₀ values of 2.29 and 10.68 µM, respectively. Moreover, 1, 2 and 6 exhibited antileishmanial activity towards Leishmania donovani with IC₅₀ values of 11.24, 15.32 and 27.27 µM, respectively and IC₉₀ values of 14.68, 40.56 and 167.03 µM, respectively.     

Production of lovastatin by wild strains of Aspergillus terreus

A wild fungal strain of Aspergillus terreus, labeled as PM3, was isolated by using the Candida albicans bioassay and confirmed by 18S r DNA analyses. Lovastatin was produced by submerged and solid state fermentations. Of the 30 isolated fungal strains, 11 showed lovastatin production with Aspergillus terreus PM3 being the best with a yield of 240 mg/L at the 10th day of submerged fermentation. Carboxymethylcellulose had a stimulatory effect on lovastatin production. It restricted uncontrolled filamentous growth, induced pellet formation and, thereby, improved lovastatin yield. In solid state fermentation (SSF), of the agro wastes from five crops (bran of wheat and rice, husks of red gram and soybean, and green gram straw), wheat bran showed maximum lovastatin production (12.5 mg/g of dry substrate) at pH 7.1 and a temperature of 30 +/- 2 degrees C. Development of a lovastatin production process based on wheat bran as a substrate in SSF is economically attractive as it is a cheap and readily available raw material in agriculture-based countries.     

Cyclic voltammetric measurements of growth of Aspergillus terreus.

A detailed study using the cyclic voltammogram was done on the live cells of Aspergillus terreus. The peak current values were obtained for different days of growth and plotted against time. The response of cyclic voltammogram showed the phases of the growth of the fungus. The growth curve obtained matched well with the conventional methodology, which assesses the increase of dry weight of the organisms against time. The electrochemical method is more advantageous because it is easy to assess and consumes less time. Further the electrochemical method clearly shows the decline phase which is generally not very defined in the conventional method of assessment of the growth curve. It was confirmed by further experiments that the metabolites were responsible for the anodic peak and not the biomass. Further work is in progress in order to analyze the metabolite(s) that is/are responsible for the anodic peak.     

Terrein Biosynthesis in Aspergillus terreus and Its Impact on Phytotoxicity

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Production,Biochemical Characterization,and Kinetic/Thermodynamic Study of Inulinase from Aspergillus terreus URM4658

Inulinases are enzymes involved in the hydrolysis of inulin, which can be used in the food industry to produce high-fructose syrups and fructo-oligosaccharides. For this purpose, different Aspergillus strains and substrates were tested for inulinase production by solid-state fermentation, among which Aspergillus terreus URM4658 grown on wheat bran showed the highest activity (15.08 U mL⁻¹). The inulinase produced by this strain exhibited optimum activity at 60 °C and pH 4.0. A detailed kinetic/thermodynamic study was performed on the inulin hydrolysis reaction and enzyme thermal inactivation. Inulinase was shown to have a high affinity for substrate evidenced by very-low Michaelis constant values (0.78–2.02 mM), which together with a low activation energy (19.59 kJ mol⁻¹), indicates good enzyme catalytic potential. Moreover, its long half-life (t_1/2 = 519.86 min) and very high D-value (1726.94 min) at 60 °C suggested great thermostability, which was confirmed by the thermodynamic parameters of its thermal denaturation, namely the activation energy of thermal denaturation (E*_d = 182.18 kJ mol⁻¹) and Gibbs free energy (106.18 ≤ ΔG*_d ≤ 111.56 kJ mol⁻¹). These results indicate that A. terreus URM4658 inulinase is a promising and efficient biocatalyst, which could be fruitfully exploited in long-term industrial applications.     

Asperterzine,a symmetric aromatized derivative of epipolythiodioxopiperazine,from the endophytic fungus Aspergillus terreus PR-P-2

A new symmetric aromatized derivative of epidithiodioxopiperazine, asperterzine (1), was isolated from the endophytic fungus Aspergillus terreus PR-P-2. The structure was elucidated by various spectroscopic and the cytotoxicity against HL-60 cell line was also evaluated.     

Biochemical Properties of Tyrosinase from Aspergillus terreus and Penicillium copticola; Undecanoic Acid from Aspergillus flavus,an Endophyte of Moringa oleifera,Is a Novel Potent Tyrosinase Inhibitor

Tyrosinase is a copper-containing monooxygenase catalyzing the O-hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine then to dopaquinone that is profoundly involved in melanin synthesis in eukaryotes. Overactivation of tyrosinase is correlated with hyperpigmentation that is metabolically correlated with severe pathological disorders, so, inhibition of this enzyme is the most effective approach in controlling the overproduction of melanin and its hazardous effects. Thus, searching for a powerful, selective inhibitor of human tyrosinase to limit the hyper-synthesis of melanin is a challenge. Unlike the difficulty of overexpression of human tyrosinase, using fungal tyrosinase as a model enzyme to the human one to evaluate the mechanistics of enzyme inhibition in response to various compounds is the most feasible strategy. Thus, the purification of highly catalytic-efficient fungal tyrosinase, exploring a novel inhibitor, and evaluating the mechanistics of enzyme inhibition are the main objectives of this work. Aspergillus terreus and Penicillium copticola were reported as the most potential tyrosinase producers. The biochemical properties suggest that this enzyme displays a higher structural and catalytic proximity to human tyrosinase. Upon nutritional bioprocessing by Plackett–Burman design, the yield of tyrosinase was increased by about 7.5-folds, compared to the control. The purified tyrosinase was strongly inhibited by kojic acid and A. flavus DCM extracts with IC₅₀ values of 15.1 and 12.6 µg/mL, respectively. From the spectroscopic analysis, the main anti-tyrosinase compounds of A. flavus extract was resolved, and verified as undecanoic acid. Further studies are ongoing to unravel the in vivo effect and cytotoxicity of this compound in fungi and human, that could be a novel drug to various diseases associated with hyperpigmentation by melanin.     

Radioactive32P incorporation in liver of mice fed with Aspergillus terreus contaminated feed

The distribution of³²P during toxicosis due to Aspergillus terreus, a common food contaminant, reported to produce the toxin terreic acid, in addition to few others, was studied in mice. Radioactive³²P was injected intraperitoneally to the control mice and the experimental ones, which were fed with Aspergillus terreus contaminated feed, as well as the toxin terreic acid. After 24 hours, both control and experimental animals were sacrificed.³²P incorporation in various fractions of liver were studied. In mice, fed with the contaminated feed, more³²P got incorporated in the nucleic acid fraction than seen in protein, barium soluble and barium insoluble fractions, whereas³²P incorporation in lipid fraction was lower.