Suillusin, a Unique Benzofuran from the Mushroom <i>Suillus </i><i>g</i><i>ranulatus</i>

A unique benzofuran named suillusin was isolated from the methanolic extract of the fruiting body of the mushroom Suillus granulatus. Its structure was assigned on the basis of various spectroscopic analyses as a highly substituted novel 1H-cyclopenta[b]benzofuran (1). Suillusin is suggested to be biogenerated from polyporic acid

New Tricyclic Sesquiterpenes from the Fermentation Broth of <i>Stereum </i><i>h</i><i>irsutum</i>

In search for novel metabolites from the culture broth of the mushroom Stereum hirsutum, three new tricyclic sesquiterpenes named hirsutenols A (1), B (2), and C (3) have been isolated. Their structures were assigned on the basis of various spectroscopic studies

Chemical Constituents of the Culture Broth of <i>Panus rudis</i>

In our ongoing search for new secondary metabolites from fungal strains, one novel compound (1) and nine known compounds (2-10) were isolated from the EtOAc-soluble layer of the culture broth of Panus rudis. The culture broth of P. rudis was extracted in acetone and fractionated by solvent partition; column chromatography using silica gel, Sephadex LH-20, and Sephadex G-10; MPLC; and HPLC. The structures of isolated compounds were elucidated by one- and two-dimensional NMR and LC-ESI-mass measurements. One new compound, panepoxydiol (1), and nine known compounds, (E)-3-(3-hydroxy-3-methylbut-1-en-1-yl)-7-oxabicyclo[4.1.0]hept-3-ene-2,5-diol (2), isopanepoxydone (3), neopanepoxydone (4), panepoxydone (5), panepophenanthrin (6), 4-hydroxy-2,2-dimethyl-6-methoxychromane (7), 6-hydroxy-2,2-dimethyl-3-chromen (8), 2,2-dimethyl-6-methoxychroman-4-one (9), 3,4-dihydroxy-2,2-dimethyl-6-methoxychromane (10), were isolated from the culture broth of P. rudis. This is the first report of isolation of a new compound panepoxydiol (1) and nine other chemical constituents (2-5, 7-10) from the culture broth of P. rudis.</p

Neuraminidase Inhibitors from the Fruiting Body of <i>Glaziella splendens</i>

Neuraminidase (NA) cleaves the glycosidic bond linkages of sialic acids to release the mature virions from infected cells and has been an attractive therapeutic target for anti-influenza agents. In our ongoing investigation of NA inhibitors in mushroom extracts, we found that the extract the fruiting body of Glaziella splendens potently inhibited neuraminidase. The fruiting bodies of G. splendens were extracted and partitioned successively with hexane, ethyl acetate, and butanol. The ethyl acetate soluble-layer was subjected to silica gel and Sephadex LH-20 column chromatographies, and MPLC to obtain five compounds (1–5). Their structures were determined by spectroscopic methods. NA inhibitory activity of these compounds was evaluated using NAs from recombinant rvH1N1, H3N2, and H5N1 influenza A viruses. One compound (1) was elucidated as a new azaphilone derivative, and four compounds (2–5) were identified as entonaemin A, comazaphilone D, rubiginosin A, and entonaemin B, respectively. Compounds 3 and 4 showed considerable inhibitory activity against three types of neuraminidases with the IC50 values of 30.9, 41.8, and 35.7 µM for 3 and 46.5, 50.4, and 29.9 µM for 4, respectively. This study reveals that the fruiting bodies of G. splendens possess azaphilone derivatives with the NA inhibitory activity. This is the first report on the isolation of neuraminidase inhibitors from the fruiting bodies of G. splendens.</p

Antifungal Activity of CHE-23C, a Dimeric Sesquiterpene from Chloranthus henryi

An antifungal compound was isolated from methanol extracts of stems and roots of Chloranthus henryi Hemsl. using ethyl acetate extraction and various chromatographic techniques. On the basis of spectroscopic analyses including mass and various NMR, the structure of the compound was identified as a dimeric sesquiterpene, CHE-23C. The compound showed potent antifungal activities (MICs = 1−32 μg/mL) in vitro against various phytopathogenic fungi such as Alternaria kikuchiana, Botrytis cinerea, Colletotrichum lagenarium, Magnaporthe grisea, Pythium ultimum, and Phytophthora infestans. In particular, it exhibited 91 and 100% disease-control activity in vivo against tomato late blight (P. infestans) and wheat leaf rust (Puccinia recondita) at concentrations of 33 and 100 μg/mL, respectively. The disease-control activity of this compound was stronger than that of the commercially available fungicide chlorothalonil, but weaker than that of dimethomorph. Therefore, the compound might serve as an interesting lead to develop effective antifungal agents

Ca²⁺-Inositol Phosphate Chelation Mediates the Substrate Specificity of β-Propeller Phytase^†

Inositol phosphates are recognized as having diverse and critical roles in biological systems. In this report, kinetic studies and TLC analysis indicate that β-propeller phytase is a special class of inositol phosphatase that preferentially recognizes a bidentate (P-Ca2+-P) formed between Ca2+ and two adjacent phosphate groups of its natural substrate phytate (InsP6). The specific recognition of a bidentate chelation enables the enzyme to sequentially hydrolyze one of the phosphate groups in a bidentate of Ca2+−InsP6 to yield a myo-inositol trisphosphate (InsP3) and three phosphates as the final products. A comparative analysis of 1H- and 13C NMR spectroscopy with the aid of 2D NMR confirms that the chemical structure of the final product is myo-Ins(2,4,6)P3. The catalytic properties of the enzyme suggest a potential model for how the enzyme specifically recognizes its substrate Ca2+−InsP6 and produces myo-Ins(2,4,6)P3 from Ca2+−InsP6. These findings potentially provide evidence for a selective Ca2+−InsPs chelation between Ca2+ and two adjacent phosphate groups of inositol phosphates

Glycopeptide Antitumor Antibiotic Zorbamycin from <i>Streptomyces </i><i>flavoviridis</i> ATCC 21892: Strain Improvement and Structure Elucidation^⊥

Zorbamycin (1, ZBM) is a glycopeptide antitumor antibiotic first reported in 1971. The partial structures of 1 were speculated on the basis of its acid hydrolysis products, but the structure of the intact molecule has never been established. The low titer of 1 from the wild-type strain, combined with its acid-instability, has so far hampered its isolation. By random mutagenesis of Streptomyces flavoviridis ATCC21892, a wild-type producer of 1, with UV irradiation, two high-producing strains of 1, S. flavoviridis SB9000 and SB9001, were isolated. Under the optimized fermentation conditions, these two strains produced about 10 mg/L of 1, which was about 10-fold higher than the wild-type ATCC21892 strain, as estimated by HPLC analysis. Finally, 1 was isolated as both a 1−Cu complex and Cu-free molecule, and the intact structure of 1 was established on the basis of a combination of mass spectrometry and 1H and 13C NMR spectroscopic analyses

Soy Leaf Extract Containing Kaempferol Glycosides and Pheophorbides Improves Glucose Homeostasis by Enhancing Pancreatic β‑Cell Function and Suppressing Hepatic Lipid Accumulation in <i>db</i>/<i>db</i> Mice

This study investigated the molecular mechanisms underlying the antidiabetic effect of an ethanol extract of soy leaves (ESL) in <i>db</i>/<i>db</i> mice. Control groups (<i>db</i>/+ and <i>db</i>/<i>db</i>) were fed a normal diet (ND), whereas the <i>db</i>/<i>db</i>-ESL group was fed ND with 1% ESL for 8 weeks. Dietary ESL improved glucose tolerance and lowered plasma glucose, glycated hemoglobin, HOMA-IR, and triglyceride levels. The pancreatic insulin content of the <i>db</i>/<i>db</i>-ESL group was significantly greater than that of the <i>db</i>/<i>db</i> group. ESL supplementation altered pancreatic <i>IRS1</i>, <i>IRS2</i>, <i>Pdx1</i>, <i>Ngn3</i>, <i>Pax4</i>, <i>Ins1</i>, <i>Ins2</i>, and <i>FoxO1</i> expression. Furthermore, ESL suppressed lipid accumulation and increased glucokinase activity in the liver. ESL primarily contained kaempferol glycosides and pheophorbides. Kaempferol, an aglycone of kaempferol glycosides, improved β-cell proliferation through IRS2-related FoxO1 signaling, whereas pheophorbide <i>a</i>, a product of chlorophyll breakdown, improved insulin secretion and β-cell proliferation through IRS1-related signaling with protein kinase A in MIN6 cells. ESL effectively regulates glucose homeostasis by enhancing IRS-mediated β-cell insulin signaling and suppressing SREBP-1-mediated hepatic lipid accumulation in <i>db</i>/<i>db</i> mice