Regulation of secondary metabolites in the endophytic fungus Penicillium sp. KMU18029 by the chemical epigenetic modifier 5-azacitidine.

The chemical epigenetic modifier 5-azacitidine (5-Aza C), a DNA methyltransferase inhibitor, was used to manipulate the endophytic fungus Penicillium sp. KMU18029. From its rice fermentation extract, a new polyketone compound (3S,4R)-3,4,8-trihydroxy-6-methyl-3,4-dihydronaphthalen-1(2H)-one (1), along with 13 known compounds, 3,4,8-trihydroxy-6-(hydroxymethyl)-3,4-dihydronaphthalen-1(2H)-one (2), decaturin B (3), 15-hydroxydecaturin A (4), oxalicine A (5), pileotin A (6), pyrandecarurin A (7), decaturenol A (8), decaturenoid (9), penisarins A (10), oxaline (11), (4E,8E)-N-D-2'-hydroxyocta-decanoyl-1-O-ß-D-glycopy-ranosyl-9-methyl-4,8-sphingadienine (12), ergosterol (13) and stigma-5-en-3-O-ß-glucoside (14), were separated. Among the known compounds, 2, 7, 12 and 14 were not found in our previous research on this strain. The structure of the new compound was identified by spectroscopic techniques such as HR-ESIMS, 1D NMR, 2D NMR and CD. Furthermore, all the isolated compounds were tested for their antimicrobial activities, and only compounds 1, 2 and 11 showed weak activities against S. aureus, with MICs of 128 µg/mL.

Fungal polyketides produced by an endophytic fungus Phoma sp. associated with Gastrodia elata.

Two novel fungal polyketides, phometides A (1) and B (2), together with four known compounds (3-6), were isolated from the endophytic fungus Phoma sp. YUD17001 obtained from Gastrodia elata Blume. The structures were elucidated based on spectroscopic analyses, X-ray crystal diffraction, and time-dependent density functional theory/electronic circular dichroism (TDDFT/ECD) calculations. Structurally, phometide A (1) represented the first example of C12 polyketide characterized by an unusual tetrahydrobenzofuran-3(2H)-one core with an α,ß-unsaturated ketone functionality, while phometide B (2) was an unprecedented molecule containing a 2-pentylcycloheptan-1-one scaffold. In an antimicrobial activity assay, phometide A (1) exhibited significant inhibitory activity against Staphylococcus aureus with MIC value of 4 µg/mL. Phometide B (2) showed moderate antifungal activity against Candida albicans with an MIC value of 16 µg/mL. Furthermore, compounds 1 and 2 were evaluated for their acetylcholinesterase inhibitory and cytotoxic activities.

Transient inhibition of mitochondrial function by chrysin and apigenin prolong longevity via mitohormesis in C. elegans.

Mild inhibition of mitochondrial function leads to longevity. Genetic disruption of mitochondrial respiratory components either by mutation or RNAi greatly extends the lifespan in yeast, worms, and drosophila. This has given rise to the idea that pharmacologically inhibiting mitochondrial function would be a workable strategy for postponing aging. Toward this end, we used a transgenic worm strain that expresses the firefly luciferase enzyme widely to evaluate compounds by tracking real-time ATP levels. We identified chrysin and apigenin, which reduced ATP production and increased the lifespan of worms. Mechanistically, we discovered that chrysin and apigenin transiently inhibit mitochondrial respiration and induce an early ROS, and the lifespan-extending effect is dependent on transient ROS formation. We also show that AAK-2/AMPK, DAF-16/FOXO, and SKN-1/NRF-2 are required for chrysin or apigenin-mediated lifespan extension. Temporary increases in ROS levels trigger an adaptive response in a mitohormetic way, thereby increasing oxidative stress capacity and cellular metabolic adaptation, finally leading to longevity. Thus, chrysin and apigenin represent a class of compounds isolated from natural products that delay senescence and improve age-related diseases by inhibiting mitochondrial function and shed new light on the function of additional plant-derived polyphenols in enhancing health and delaying aging. Collectively, this work provides an avenue for pharmacological inhibition of mitochondrial function and the mechanism underlining their lifespan-extending properties.

Bioactive sorbicillinoids from a rhizospheric soil-derived Paecilomyces sp. KMU21009.

A new hybrid sorbicillinoid named paeciureallin (1) and a new monomeric sorbicillinoid named paecillyketide (2), along with six known analogues (3-8), were isolated from the rhizospheric soil-derived fungus Paecilomyces sp. KMU21009 associated with Delphinium yunnanense. Their structures were elucidated by extensive spectroscopic analysis and comparison with literature values. Paeciureallin (1) is the first example of hybrid sorbicillinoids possessing a rare sorbicillinoid urea unit and containing a ß-D-ribofuranose functionality. In pharmacological studies, compounds 1 and 2 were evaluated for in vitro anti-inflammatory and cytotoxic activities. Paeciureallin (1) exhibited moderate cytotoxicity against SW480 and A549 cell lines, and the IC50 values were 32.0 ± 0.1 and 34.4 ± 2.0 µM, respectively.

Penisarins A and B, Sesquiterpene Coumarins Isolated from an Endophytic Penicillium sp.

Penisarins A (1) and B (2), sesquiterpene coumarins with an unusual tricyclic sesquiterpene system, were isolated from endophytic Penicillium sp. KMU18029. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compound 2 showed significant cytotoxicities against two human cancer cell lines, HL-60 and SMMC-7721, with IC50 values of 3.6 ± 0.2 and 3.7 ± 0.2 µM, respectively.