Yuichi Yamaguchi

Effect of sea water concentration on hyphal growth and antimicrobial metabolite production in marine fungi

We studied the effect of sea water concentration in a culture medium on fungal growth and the production of antimicrobial metabolites. Most of the marine fungal isolates were identified as members of the same genera as terrestrial isolates, such asAspergillus andTrichoderma. Many of the marine fungi isolated grew more abundantly as the sea water concentration increased. The production of antimicrobial materials was improved as the sea water concentration increased. Even though the marine fungi were considered to be similar to fungi from terrestrial environments, from a mycological perspective, the two types have different physiological characteristics. The fungi from marine samples are useful microbial resources in the search for new bioactive compounds.

Tensidols, New Potentiators of Antifungal Miconazole Activity, Produced by Aspergillus niger FKI-2342

Two new furopyrrols, designated tensidols A and B, were isolated from the culture broth of Aspergillus niger FKI-2342 by solvent extraction, silica gel column chromatography and HPLC. Their structures were elucidated and shown to have the common skeleton of 6-benzyl-6H-furo[2,3-b]pyrrole. Tensidols A and B potentiated miconazole activity against Candida albicans. Tensidols also showed moderate antimicrobial activity only against Pyricularia oryzae.

Citridones, new potentiators of antifungal miconazole activity, produced by Penicillium sp. FKI-1938. I. Taxonomy, fermentation, isolation and biological properties.

New phenylfuropyridinones and related compounds, designated citridones A, B, B′ and C, were isolated along with known CJ-16,173, from the culture broth of Penicillium sp. FKI-1938 by solvent extraction, silica gel column chromatography and HPLC. Citridones (75 µM) potentiate the miconazole activity against Candida albicans, decreasing the IC50 value of miconazole from 14.5 nM to 3.5∼6.3 nM.

Stemphones, Novel Potentiators of Imipenem Activity against Methicillin-resistant Staphylococcus aureus, Produced by Aspergillus sp. FKI-2136

A fungal strain FKI-2136 identified as genus Aspergillus was found to produce potentiators of imipenem activity against methicillin-resistant Staphylococcus aureus (MRSA). Two new compounds designated stemphones B and C were isolated along with a structurally related known compound cochlioquinone D from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography and preparative HPLC. These compounds have a common tetracyclic quinone skeleton. Stemphone C potentiated imipenem activity against the MRSA 512 fold by decreasing MIC value of imipenem from 16 µg/ml to 0.03 µg/ml.

Yaequinolones, new insecticidal antibiotics produced by Penicillium sp. FKI-2140. I. Taxonomy, fermentation, isolation and biological activity.

New nine insecticidal antibiotics designated yaequinolones were isolated from the culture broth of the fungal strain Penicillium sp. FKI-2140 by solvent extraction, centrifugal partition chromatography and HPLC. Yaequinolones showed growth inhibitory activity against brine shrimp (Artemia salina). Among them, yaequinolone F has the most potent activity with MIC value of 0.19 μg/ml.

Fungal phenalenones inhibit HIV-1 integrase.

AbstractA phenalenone compound, atrovenetinone methyl acetal, was isolated from a culture broth of Penicillium sp. FKI-1463 as an HIV-1 integrase inhibitor, and it showed anti-HIV activity in vitro. HIV-1 integrase inhibition and anti-HIV activity of two other natural phenalenones were also studied. Among the tested compounds, funalenone inhibited HIV-1 integrase with an IC50 value of 10 µM and showed the best selectivity (anti-HIV, IC50=1.7 µM; cytotoxicity, IC50=87 µM).

Spylidone, a novel inhibitor of lipid droplet accumulation in mouse macrophages produced by Phoma sp. FKI-1840.

During our screening for microbial inhibitors of lipid droplet accumulation in macrophages, a new compound designated spylidone was isolated along with two structurally related known compounds, PF1052 and vermisporin, from the fermentation broth of Phoma sp. FKI-1840 by solvent extraction, silica gel column chromatography, ODS column chromatography and preparative HPLC. From the structure elucidation, spylidone has a spiro ring containing 2,4-pyrrolidinedione. Among the three compounds, only spylidone was found to inhibit lipid droplet accumulation in macrophages at 10∼50 µM without any cytotoxic effect.

Verticipyrone, a New NADH-fumarate Reductase Inhibitor, Produced by Verticillium sp. FKI-1083

A new NADH-fumarate reductase inhibitor, verticipyrone, was isolated from the cultured broth of a fungus, Verticillium sp. FKI-1083. The structure was established as (E)-2-methoxy-3,5-dimethyl-6-(3-methyl-2-undecenyl)-4H-pyran-4-one. Verticipyrone exhibited an IC50 value of 0.88 nM against NADH-fumarate reductase of Ascaris suum. Verticipyrone inhibited both Ascaris and bovine heart complex I, and its synthetic analogue, 8,9-dihydro-8-hydroxyverticipyrone, showed good selectivity against Ascaris complex I.

Verticilide, a new ryanodine-binding inhibitor, produced by Verticillium sp. FKI-1033.

A new ryanodine-binding inhibitor, verticilide, was isolated from the cultured broth of a fungus, Verticillium sp. FKI-1033. It is a 24-membered ring cyclic depsipeptide, its structure being elucidated as cyclo[(2R)-2-hydroxyheptanoyl-N-methyl- L-alanyl]4. Verticilide inhibited ryanodine binding to ryanodine receptors in the cockroach at an IC50 value of 4.2 μM, whereas inhibition against mouse ryanodine receptors was weak (IC50=53.9 μM).

Taxonomy and secondary metabolites of Pseudobotrytis sp. FKA-25

Fungal strain FKA-25, isolated from forest soil collected on Yakushima Island, Kagoshima Prefecture, Japan, was assigned to genus Pseudobotrytis based on its morphological characteristics. Conidiophores were erect, slightly swollen at the end of the tip, and gave rise to umbellate conidiogenous cells that were in an expanded denticulate portion at the end and formed ellipsoidal to clavate conidia in sympodial succession. Identification as species P. terrestris was made on the basis of the character of 1-septate conidium. Although no secondary metabolites have been reported from the genus Pseudobotrytis, four secondary metabolite compounds (designated A to D) were isolated from the culture broth of strain FKA-25. Compounds B to D have been reported previously as FK-17-p2a, lunatinin, and 3,4-dihydro-3,4,8-trihydroxy-1(2H)-naphthalenone, respectively. Compound A was designated sespendole and possessed a novel indole-sesquiterpene skeleton.