Yasunori Ono

Colletoic Acid, a Novel 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor from Colletotrichum gloeosporioides SANK 21404

Colletoic acid, a novel 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor, was found and isolated from the cultured broth of the producing fungus Colletotrichum gloeosporioides SANK 21404. Its structure was determined to be a novel acorene-type sesquiterpene by several spectroscopic methods. The absolute structure of colletoic acid was established using a modified Moshers method and single-crystal X-ray diffraction analysis.

Novel Nrf2 activators from microbial transformation products inhibit blood–retinal barrier permeability in rabbits

Nuclear factor erythroid 2‐related factor 2 (Nrf2) is a redox‐sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of the Nrf2 pathway seems protective for many organs, and although a well‐known Nrf2 activator, bardoxolone methyl, was evaluated clinically for treating chronic kidney disease, it was found to induce adverse events. Many bardoxolone methyl derivatives, mostly derived by chemical modifications, have already been studied. However, we adopted a biotransformation technique to obtain a novel Nrf2 activator.

Notes on new and noteworthy plant-inhabiting fungi in Japan (3)

Six fungi isolated from plant materials in Japan are described. The first isPseudohalonectria aomoriensis sp. nov. (Lasiosphaeriaceae). It differs from other known species of the genusPseudohalonectria in the dimensions of its asci and ascospores. The second,Monodictys abuensis, is newly added to the mycoflora of Japan. Its host,Zelkova serrata, is also newly recorded. Three others found on new host plants areDictyochaeta simplex onQuercus myrsinaefolia andBladhia crispa, Colletotrichum dematium onAucuba japonica var.borealis, andNectria mammoidea var.rubi onCercidiphyllum japonicum. The sixth,Trochophora fasciculata, aDaphniphyllum sooty leaf spot fungus renamed by Goos fromT. simplex, is reported with a full list of synonyms.

Ascotricins A and B, novel antagonists of sphingosine-1-phosphate receptor 1 from Ascotricha chartarum Berk. SANK 14186

Ascotricins A and B were isolated as novel sphingosine-1-phosphate receptor 1 (S1P1) antagonists from a cultured broth of a fungus identified as Ascotricha chartarum Berk. SANK 14186. The two compounds were purified by solvent extraction, reversed-phase (RP) column chromatography and a preparative RP-HPLC. The structures were determined by various NMR experiments and by LC/MS and GC/MS analyses. The S1P1 antagonist activities were measured by a cyclic AMP assay using S1P1-expressing cells and the IC50 values were 8.2 and 1.8 μM, respectively. In a [33P]sphingosine-1-phosphate/S1P1-binding assay, those values were 120 and 39 μM, and in a migration assay using human umbilical vein endothelial cells (HUVECs), they were 94 and 28 μM, respectively. Thus, ascotricins A and B are novel S1P1 antagonists showing an inhibition activity toward HUVEC migration.

Hyaloscyphaceae in Japan (5): Some Lachnum-like members*

Five members of the family Hyaloscyphaceae with multiseptate hairs and lanceolate paraphyses (Lachnum-like members in broad sense) are described:Albotricha fagicola andDasyscyphella longistipitata spp. nov.;Trichopeziza discolor, T. sulphurea, andTrichopezizella barbata, new to Japan.

Biosynthesis of nectrisine in Thelonectria discophora SANK 18292.

Nectrisine, an iminosugar with a heterocyclic nitrogen-containing 5-membered ring, acts as a glycosidase inhibitor. Thelonectria discophora SANK 18292, a fungus, was identified as a nectrisine producer from its microbial library in our screening for nectrisine producing microorganisms. Biosynthesis of nectrisine produced by the fungus was studied using stable isotope tracer techniques. Incorporation of (13)C-labeled d-ribose and d-xylose into nectrisine was confirmed by mass spectrometry and (13)C NMR spectroscopy, which suggested that these were its precursors. Chromatographic separation of the hot water extract from the culture broth afforded not only nectrisine, but also substantial amounts of 4-amino-4-deoxyarabinitol. Incubation of the latter with the crude enzyme of the fungus at room temp. caused an increase in levels of nectrisine together with a decrease in amounts of the administered potential precursor suggesting that it is a biosynthetic intermediate. From these results, a biosynthetic pathway to nectrisine is proposed via d-xylulose 5-phosphate and 4-amino-4-deoxyarabinitol by the pentose phosphate pathway.

Haplofungins, novel inositol phosphorylceramide synthase inhibitors, from Lauriomyces bellulus SANK 26899 I. Taxonomy, fermentation, isolation and biological activities

In the course of screening for antifungal agents, we have discovered eight novel compounds, haplofungin A, B, C, D, E, F, G and H, from a culture broth of the fungus strain Lauriomyces bellulus SANK 26899. Haplofungins are composed of an arabinonic acid moiety linked through an ester to a modified long alkyl chain and show potent inhibitory activities against fungal inositol phosphorylceramide (IPC) synthase. Haplofungin A inhibited the activity of IPC synthase from Saccharomyces cerevisiae with an IC50 value of 0.0015 μg ml−1. This inhibitor also suppressed the growth of Candida glabrata at the MIC value of 0.5 μg ml−1.

A new species of Pestalosphaeria, the teleomorph of Pestalotiopsis neglecta.

Three specimens of a newPestalosphaeria species were obtained from a twig ofQuercus myrsinaefolia from Kumamoto Pref., and from leaves ofRhododendron hybridum andRicinus communis from Izu Peninsula, Shizuoka Pref. The collected materials were kept moist for 1 to 2 mo after collection. Monoascospore isolates from each specimen produced identical colonies with black slimy masses of conidia on them. Morphological characteristics of the conidia accorded well with those ofPestalotiopsis neglecta not only hitherto recorded but also formed on the same specimen. Hence,Pestalosphaeria gubae sp. nov. is proposed for the new species, as the teleomorph ofPestalotiopsis neglecta.

Gummy stem blight of balsam pear caused by Didymella bryoniae and its anamorph Phoma cucurbitacearum

Gummy stem blight of balsam pear found in the Kanto district and in the Hokkaido Prefecture was demonstrated to be caused by Didymella bryoniae (Auerswald) Rehm based on inoculation experiments, molecular analysis, and morphological identification of the pathogenic fungus. This fungus was also pathogenic to related plants belonging to Cucurbitaceae. The imperfect stage of the fungus was identified as Phoma cucurbitacearum (Fr.: Fr.) Sacc. based on morphological similarities.

Notes on various plant-inhabiting fungi from Hachijo Island, Tokyo (1)

Among plant-inhabiting fungi collected in June 2001 and in September 2002 on Hachijo Island, Tokyo, four fungi are described in this article. They consist of two new species, namely Stagonospora hachijoensis on Miscanthus sinensis var. condensatus and Ascochyta ixorae on Ixora chinensis, and two fungi newly added to the Japanese mycoflora, namely Discosiella cylindrospora on Callistemon speciosum and Robillarda sessilis on Parthenocissus tricuspidatus.