Oral adjuvant activity for nasal influenza vaccines caused by combination of two trihydroxy fatty acid stereoisomers from the tuber of Pinellia ternata.

Pinellic acid from the tuber of Pinellia ternata was isolated as an effective oral adjuvant for nasal influenza vaccine, and identified 9S,12S,13S-trihydroxy-10E-octadecenoic acid (9S,12S,13S) by the enantioselective total synthesis [Nagai et al., Int. Immunopharmacol.

New rugulosins, anti-MRSA antibiotics, produced by Penicillium radicum FKI-3765-2.

New rugulosins B (2) and C (3) were isolated together with known rugulosin (renamed rugulosin A in this paper, 1) from whole culture of Penicillium radicum FKI-3765-2, and their structures were elucidated by NMR spectroscopy. Rugulosins A and C were a homodimer of the same anthraquinone moieties, whereas rugulosin B was a heterodimer of analogous anthraquinone moieties. Rugulosins A to C showed antimicrobial activity against methicillin-resistant Staphylococcus aureus.

Improved catalytic and stereoselective glycosylation with glycosyl N-trichloroacetylcarbamate: application to various 1-hydroxy sugars.

Efficient catalytic and stereoselective glycosylation was achieved by activating a glycosyl N-trichloroacetylcarbamate with a catalytic amount of Lewis acid in the presence of a glycosyl acceptor and 5A molecular sieves. Catalytic one-pot dehydrative glycosylation of a 1-hydroxy carbohydrate was achieved stereoselectively by reaction with trichloroacetyl isocyanate, followed by activation with a catalytic amount of activators.

Nosokomycins, new antibiotics discovered in an in vivo-mimic infection model using silkworm larvae. II: Structure elucidation.

The structures of nosokomycins A, B, C and D, new anti-methicillin-resistant Staphylococcus aureus antibiotics produced by Streptomyces sp. K04-0144, were elucidated by spectroscopic studies including various NMR experiments. Nosokomycins A, B, C and D are new members of the moenomycin family consisting of an oligosaccharide moiety, a 2,3-dihydroxypropionic acid and an unusual sesterterpenoid moiety.

Calpinactam, a new anti-mycobacterial agent, produced by Mortierella alpina FKI-4905.

Calpinactam, a new anti-mycobacterial agent, was isolated from the culture broth of a fungal strain Mortierella alpina FKI-4905 by solvent extraction, octadecyl silane column chromatography and preparative HPLC. Calpinactam was active only against Mycobacteria among various microorganisms, including Gram-positive and Gram-negative bacteria, fungi and yeasts. Calpinactam inhibited the growth of Mycobacterium smegmatis and Mycobacterium tuberculosis with MIC values of 0.

Nosokomycins, new antibiotics discovered in an in vivo-mimic infection model using silkworm larvae. I: Fermentation, isolation and biological properties.

The in vivo-mimic assay system using silkworm larvae was used as a screening tool to discover antibiotics against methicillin-resistant Staphylococcus aureus (MRSA). Microbial culture broths were screened in this in vivo-mimic assay system and a culture broth of Streptomyces sp. K04-0144 was selected.

Recent development of two chitinase inhibitors, Argifin and Argadin, produced by soil microorganisms.

Chitin, the second most abundant polysaccharide in nature, occurs in fungi, some algae and many invertebrates, including insects. Thus, chitin synthesis and degradation could represent specific targets for fungicides and insecticides. Chitinases hydrolyze chitin into oligomers of N-acetyl-D-glucosamine at key points in the life cycles of organisms, consequently, chitinase inhibitors have become subject of increasing interest.

Genome-minimized Streptomyces host for the heterologous expression of secondary metabolism.

To construct a versatile model host for heterologous expression of genes encoding secondary metabolite biosynthesis, the genome of the industrial microorganism Streptomyces avermitilis was systematically deleted to remove nonessential genes. A region of more than 1.4 Mb was deleted stepwise from the 9.

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).

Phytohabitans suffuscus gen. nov., sp. nov., an actinomycete of the family Micromonosporaceae isolated from plant roots.

An actinomycete strain, K07-0523(T), was isolated from the roots of an orchid collected in Okinawa prefecture, Japan. 16S rRNA gene sequence analysis indicated that the new strain belonged to the family Micromonosporaceae and the similarity values between strain K07-0523(T) and the type species of 24 genera in the family Micromonosporaceae were 93.3-97.

Structure and total synthesis of fungal calpinactam, a new antimycobacterial agent.

A new fungal metabolite designated calpinactam (1) was isolated from the culture broth of Mortierella alpina FKI-4905, and its structure was elucidated by spectroscopic analyses including NMR experiments. Calpinactam was found to be a hexapeptide with a caprolactam ring at its C-terminal. Its absolute stereochemistry was determined by amino acid analysis and total synthesis.

Production of a new type of amidepsine with a sugar moiety by static fermentation of Humicola sp. FO-2942.

Static fermentation of amidepsine-producing fungus Humicola sp. FO-2942 led to the production of six new amidepsines, including a new type of glycosylated congener. Non-glycosylated amidepsine J inhibited both human diacylglycerol acyltransferases 1 (DGAT1) and DGAT2 with the same IC(50) value of 40 muM, whereas glycosylated amidepsines F to I showed very weak inhibitory activity against DGAT1 and DGAT2.

Solid-phase synthesis and biological activity of malformin C and its derivatives.

We accomplished the solid-phase total synthesis of malformin C, which is adaptable for the easy preparation of various derivatives. A solid-phase total synthesis of malformin C was achieved by on-resin macrolactamization and disulfide bond formation, with concurrent cleavage from the resin. Antimalarial and antitrypanosomal activities were examined, which helped elucidate partial structure-activity relationships.

Mechanism by which the lectin actinohivin blocks HIV infection of target cells.

Various lectins have attracted attention as potential microbicides to prevent HIV transmission. Their capacity to bind glycoproteins has been suggested as a means to block HIV binding and entry into susceptible cells. The previously undescribed lectin actinohivin (AH), isolated by us from an actinomycete, exhibits potent in vitro anti-HIV activity by binding to high-mannose (Man) type glycans (HMTGs) of gp120, an envelope glycoprotein of HIV.

Demequina salsinemoris sp. nov., isolated on agar media supplemented with ascorbic acid or rutin.

Three strains, KV-810(T), KV-811 and KV-816, were isolated from mangrove soil from a southern island in Japan on media supplemented with ascorbic acid or rutin. These strains contained l-ornithine as the diagnostic diamino acid in the cell-wall peptidoglycan and DMK-9(H(4)) as the predominant menaquinone. The G+C content of the DNA was 70-72 mol%.

Molecular modeling of human acidic mammalian chitinase in complex with the natural-product cyclopentapeptide chitinase inhibitor argifin.

Human acidic mammalian chitinase (hAMCase) is an attractive target for developing anti-asthma medications. We used a variety of computational methods to investigate the interaction between hAMCase and the natural-product cyclopentapeptide chitinase inhibitor argifin. The three-dimensional structure of hAMCase was first constructed using homology modeling.

Rapid detection of vaginal Candida species by newly developed immunochromatography.

For the diagnosis of vulvovaginal candidiasis, we developed a simple immunochromatographic method that enables the detection of vaginal Candida spp. within about 30 min. Overall, the sensitivity, specificity, positive predictive value, and negative predictive value of this method appeared to be 80.

Xanthoradones, new potentiators of imipenem activity against methicillin-resistant Staphylococcus aureus, produced by Penicillium radicum FKI-3765-2: I. Taxonomy, fermentation, isolation and biological properties.

The fungal strain FKI-3765-2, identified as Penicillium radicum, was found to produce potentiators of imipenem activity against methicillin-resistant Staphylococcus aureus (MRSA). Two new compounds, designated xanthoradones A and B, were isolated from the fermentation broth of the producing strain by solvent extraction, octadecyl silyl column chromatography and preparative HPLC. Xanthoradones A and B potentiated imipenem activity against MRSA by decreasing the MIC value of imipenem from 16 microg ml(-1) to 0.

Xanthoradones, new potentiators of imipenem activity against methicillin-resistant Staphylococcus aureus, produced by Penicillium radicum FKI-3765-2 II. Structure elucidation.

The structures of xanthoradones A and B, new potentiators of imipenem activity against methicillin-resistant Staphylococcus aureus produced by Penicillium radicum FKI-3765-2, were elucidated by spectroscopic studies, including various NMR experiments. These compounds have an asymmetric biaryl skeleton, which contains dihydronaphthopyranone and naphthoquinone moieties.

Ilumatobacter fluminis gen. nov., sp. nov., a novel actinobacterium isolated from the sediment of an estuary.

Bacterial strain YM22-133T was isolated from the sediment of an estuary and grew in media with an artificial seawater base. Strain YM22-133T was Gram-positive, aerobic, non-motile and rod shaped. The cell-wall peptidoglycan contained LL-DAP, glycine, alanine and hydroxyglutamate.

Effect of erythromycin A and its new derivative EM201 on type I collagen production by cultured dermal fibroblasts.

Thinning of the dermis is the principal histological change in atrophic skin disorders and aged skin. It is caused due to a decreased amount of collagen in the dermis. Macrolides have been reported to exert various pharmacological activities, including anti-inflammatory activity, tumor angiogenesis inhibition and growth inhibition of fibroblasts, in addition to antimicrobial activity.

Solid-phase total synthesis of the chitinase inhibitor Argadin using a supported acetal resin.

A versatile solid-phase total synthesis was applied to the rapid preparation of Argadin, a natural product isolated and characterized as a cyclopentapeptide by our group, which possesses superior inhibitory activity against family-18 chitinases. The synthetic strategy includes peptide synthesis by using an Fmoc (9-fluorenylmethoxycarbonyl) protective group, macrolactamization, acetylguanylation and formation of hemiaminal accompanied by total deprotection, including cleavage from resin.

Polymyxin B identified as an inhibitor of alternative NADH dehydrogenase and malate: quinone oxidoreductase from the Gram-positive bacterium Mycobacterium smegmatis.

Tuberculosis is the leading cause of death due to a single infectious agent in the world and the emergence of multidrug-resistant strains prompted us to develop new drugs with novel targets and mechanism. Here, we screened a natural antibiotics library with Mycobacterium smegmatis membrane-bound dehydrogenases and identified polymyxin B (cationic decapeptide) and nanaomycin A (naphtoquinone derivative) as inhibitors of alternative NADH dehydrogenase [50% inhibitory concentration (IC(50)) values of 1.6 and 31 microg/ml, respectively] and malate: quinone oxidoreductase (IC(50) values of 4.

Siccanin rediscovered as a species-selective succinate dehydrogenase inhibitor.

To identify antibiotics targeting to respiratory enzymes, we carried out matrix screening of a structurally varied natural compound library with Pseudomonas aeruginosa membrane-bound respiratory enzymes. We identified a succinate dehydrogenase inhibitor, siccanin (IC(50), 0.9 microM), which is a potent antibiotic against some pathogenic fungi like Trichophyton mentagrophytes and inhibits their mitochondrial succinate dehydrogenase.