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Yasuhiro Igarashi

Publications and source records attributed to Yasuhiro Igarashi.

At least 37 records · Page 2Linked to original sources
PubMed2004

Directed biosynthesis of fluorinated pseurotin A, synerazol and gliotoxin.

Aspergillus fumigatus TP-F0196 produces pseurotin A, synerazol and gliotoxin. Phenylalanine is a common biosynthetic precursor of these antibiotics. Feeding fluorophenylalanine to the culture induced the production of novel fluorinated analogs. These fluorinated antibiotics were obtained from the culture broth by solvent extraction and purified by chromatographies, and their antimicrobial and antitumor activities were investigated. Among the novel fluorinated analogs, 19- and 20-fluorosynerazols exhibited potent anti-angiogenic activity in the chorioallantoic membrane assay. In addition, 19-fluorosynerazol showed more potent cytocidal activity against several cancer cell lines than synerazol.

Angiogenesis Inhibitors↗
PubMed2004

[Lactate].

Explore the source record for details and available documents.

Humans↗
PubMed2003

DNA alkylation properties of yatakemycin.

Yatakemycin represents the newest and now most potent member of a class of naturally occurring antitumor compounds that includes CC-1065 and the duocarmycins, which derive their biological properties from a characteristic DNA alkylation reaction. Herein, the first description of the yatakemycin DNA alkylation properties is detailed, constituting the first such study of a naturally occurring "sandwiched" member of this class. Thus, the event, sequence selectivity, relative rate and efficiency, and reversibility of the DNA alkylation reaction of yatakemycin are described.

Alkylation↗
PubMed2003

Concerted interaction between conjugated double bond CHs and multiple OHs in polyene macrolide antibiotic chainin: weak =C-H...O interactions responsible for intrinsic molecular assembly.

The concerted interactions observed between five conjugated double bond CHs and four hydroxy Os in the crystal of chainin, a polyene macrolide antibiotic, clarified the existence of unprecedented, weak =C-H...O interactions, which is important for forming its intrinsic molecular assembly.

Anti-Bacterial Agents↗
PubMed2003

Characterization of the biosynthetic gene cluster of rebeccamycin from Lechevalieria aerocolonigenes ATCC 39243.

The biosynthetic gene cluster for rebeccamycin, an indolocarbazole antibiotic, from Lechevalieria aerocolonigenes ATCC 39243 has 11 ORFs. To clarify their functions, mutants with rebG, rebD, rebC, rebP, rebM, rebR, rebH, rebT, or orfD2 disrupted were constructed, and the gene products were examined. rebP disruptants produced 11,11'-dichlorochromopyrrolic acid, found to be a biosynthetic intermediate by a bioconversion experiment. Other genes encoded N-glycosyltransferase (rebG), monooxygenase (rebC), methyltransferase (rebM), a transcriptional activator (rebR), and halogenase (rebH). rebT disruptants produced rebeccamycin as much as the wild strain, so rebT was probably not involved in rebeccamycin production. Biosynthetic genes of staurosporine, an another indolocarbazole antibiotic, were cloned from Streptomyces sp. TP-A0274. staO, staD, and staP were similar to rebO, rebD, and rebP, respectively, all of which are responsible for indolocarbazole biosynthesis, But a rebC homolog, encoding a putative enzyme oxidizing the C-7 site of pyrrole rings, was not found in the staurosporine biosynthetic gene cluster. These results suggest that indolocarbazole is constructed by oxidative decarboxylation of chromopyrrolic acid (11,11'-dichlorochromopyrrolic acid in rebeccamycin) generated from two molecules of tryptophan by coupling and that the oxidation state at the C-7 position depends on the additional enzyme(s) encoded by the biosynthetic genes.

Aminoglycosides↗
PubMed2003

Pradimicin-resistance of yeast is caused by a point mutation of the histidine-containing phosphotransfer protein Ypd1.

Pradimicin is an antifungal antibiotic which induces apoptosis like cell death in the yeast Saccharomyces cerevisiae. Pradimicin-resistant mutants were isolated from the S. cerevisiae and the mutation points were analyzed. A point mutation of YPD1 that led to a substitution of the 74th glycine (Gly74) to cysteine (Cys) was identified in a mutant strain NH1. In S. cerevisiae, Ypd1 transfers a phosphoryl group from the sensor kinase Slnl to the response regulator Sskl which regulates a downstream MAP kinase in response to hyperosmotic stress. Gly74 is located in a three-residue reverse turn domain that connects two alpha-helices, one of which contains a histidine residue which is phosphorylated. In the reverse turn, glycine (relative position +10 to the active-site histidine) is highly conserved in Ypd1 and other histidine-containing phosphotransfer proteins. It was therefore suggested that the substitution of Gly74 to Cys altered the Ypd1 structure, which resulted in the resistance to pradimicin.

Anthracyclines↗
PubMed2003

Yatakemycin, a novel antifungal antibiotic produced by Streptomyces sp. TP-A0356.

In the screening of novel antifungal compounds, yatakemycin was found in the culture broth of Streptomyces sp. TP-A0356. Yatakemycin was obtained by solvent extraction of the fermentation broth and chromatographic purification using ODS column and preparative HPLC. The structure of yatakemycin was elucidated by NMR and CID-MS/MS experiments as a novel antibiotic belonging to a family of CC-1065 and duocarmycins known to be DNA alkylating agents. Yatakemycin inhibited the growth of pathogenic fungi such as Aspergillus fumigatus and Candida albicans with the MIC values of 0.01-0.03 microg/ml, more potent than amphotericin B (MIC: 0.1-0.5 microg/ml) or itraconazole (MIC: 0.03-0.2 microg/ml). It also showed potent cytotoxicity against cancer cell lines with the IC50 of 0.01-0.3 microg/ml.

Antifungal Agents↗
PubMed2003

Clethramycin, a new inhibitor of pollen tube growth with antifungal activity from Streptomyces hygroscopicus TP-A0623. I. Screening, taxonomy, fermentation, isolation and biological properties.

The cytoskeletal proteins, actin and myosin, play a central role in pollen tube growth. The pollen tube growth is inhibited by cytochalasin, which interferes with actin polymerization. In the screening of pollen tube growth inhibitors, clethramycin was found from the fermentation broth of an actinomycete strain TP-A0623. The producing strain was isolated from a root of Clethra barbinervis collected in Toyama, Japan and identified as Streptomyces hygroscopicus based on the taxonomic study. Clethramycin showed in vitro antifungal activity against yeast such as Candida albicans and C. glabrata with the MIC of 0.5 approximately 8 microg/ml, but weak activity against Gram-positive and negative bacteria (MIC > or = 64 microg/ml). Cytotoxicity of clethramycin was moderate and the IC50 was 57 microg/ml against HeLa cells and 120 microg/ml against WI-38 cells.

Animals↗
PubMed2003

Clethramycin, a new inhibitor of pollen tube growth with antifungal activity from Streptomyces hygroscopicus TP-A0623. II. Physico-chemical properties and structure determination.

Clethramycin is a novel linear polyene polyketide produced by a plant-associated actinomycete Streptomyces hygroscopicus TP-A0623. It possesses a guanidino and carboxyl residue at each end and an O-sulfate group and a hexaene moiety in the molecule, and its molecular formula is C63H99N3O18S. The structure was determined by analyzing 2D-NMR and FAB-MS data, using 13C-enriched compounds. Clethramycin is structurally similar to linearmycin, an inhibitor of spheroplast regeneration in Candida albicans. Clethramycin shows potent antifungal and pollen tube growth inhibitory activity.

Antifungal Agents↗
PubMed2003

Apoptosis-like cell death of Saccharomyces cerevisiae induced by a mannose-binding antifungal antibiotic, pradimicin.

Pradimicin A (PRM), a mannose-binding antifungal antibiotic, induced the apotosis-like cell death in Saccharomyces cerevisiae. The nuclear breakage and DNA fragmentation were observed in yeast cells by DAPI and TUNEL staining after the treatment with PRM. Accumulation of reactive oxygen species (ROS) was also detected in PRM-treated yeast cells by staining with dichlorodihydrofluorescein diacetate. PRM-induced cell death and the accumulation of ROS were prevented by pretreating the yeast cells with a radical scavenger, N-acetylcysteine. These results indicate that PRM induces the apoptosis-like cell death in yeast through the generation of ROS.

Anthracyclines↗
PubMed2003

pTOYAMAcos, pTYM18, and pTYM19, actinomycete-Escherichia coli integrating vectors for heterologous gene expression.

A novel shuttle integration cosmid vector (pTOYAMAcos), based on pKU402, and shuttle integration vectors (pTYM18 and pTYM19) were constructed for the cloning of actinomycete DNA and its heterologous expression. These vectors contain oriT of an IncP transmissible plasmid in order to transfer genes by conjugation from Escherichia coli to actinomycetes, and they also contain int derived from actinophage phiC31 in order to integrate site-specifically into the chromosomal DNA. pTOYAMAcos contains the lambdacos site to promote packaging of vectors containing 35 to approximately 45-kb DNA fragments into lambda particles. pTYM18 and pTYM19 contain kanamaycin and thiostrepton resistance genes, respectively, and have multiple cloning sites including EcoRI and HindIII sites, which are available for blue/white screening in E. coli. To demonstrate the utility of these vectors, we expressed the entire gene cluster for rebeccamycin biosynthesis from Lechevalieria aerocolonigenes using pTOYAMAcos and detected rebeccamycin production in transformed S. lividans. In addition, we demonstrated the utility of pTYM 19 in a gene-disruption complementation test. L. aerocolonigenes deltarebC strain, which is defective in rebeccamycin production because of a rebC deletion, was restored to rebeccamycin production by complemention by rebC cloned in pTYM 19.

Actinobacteria↗
PubMed2002

Cloning of the staurosporine biosynthetic gene cluster from Streptomyces sp. TP-A0274 and its heterologous expression in Streptomyces lividans.

Staurosporine is a representative member of indolocarbazole antibiotics. The entire staurosporine biosynthetic and regulatory gene cluster spanning 20-kb was cloned from Streptomyces sp. TP-A0274 and sequenced. The gene cluster consists of 14 ORFs and the amino acid sequence homology search revealed that it contains three genes, staO, staD, and staP, coding for the enzymes involved in the indolocarbazole aglycone biosynthesis, two genes, staG and staN, for the bond formation between the aglycone and deoxysugar, eight genes, staA, staB, staE, staJ, staI, staK, staMA, and staMB, for the deoxysugar biosynthesis and one gene, staR is a transcriptional regulator. Heterologous gene expression of a 38-kb fragment containing a complete set of the biosynthetic genes for staurosporine cloned into pTOYAMAcos confirmed its role in staurosporine biosynthesis. Moreover, the distribution of the gene for chromopyrrolic acid synthase, the key enzyme for the biosynthesis of indolocarbazole aglycone, in actinomycetes was investigated, and rebD homologs were shown to exist only in the strains producing indolocarbazole antibiotics.

Amino Acid Sequence↗
PubMed2002

Kosinostatin, a quinocycline antibiotic with antitumor activity from Micromonospora sp. TP-A0468.

Kosinostatin, a quinocycline antibiotic was isolated from the culture broth of an actinomycete strain TP-A0468 along with isoquinocycline B. The producing strain was isolated from the seawater sample collected in Toyama Bay and identified as Micromonospora sp. based on the taxonomic study. Kosinostatin was obtained from the culture fluid by solvent extraction and ODS column chromatography. Kosinostatin inhibited the growth of Gram-positive bacteria strongly (MIC=0.039 microg/ml) and Gram-negative bacteria and yeasts moderately (MIC= 1.56 approximately 12.5 microg/ml). It showed cytotoxicity against various cancer cell lines with the IC50 of 0.02 approximately 0.6 microm and inhibited human DNA topoisomerase Ila with the IC50 of 3 approximately 10 microM.

Aminoglycosides↗
PubMed2002

NMR analysis of quinocycline antibiotics: structure determination of kosinostatin, an antitumor substance from Micromonospora sp. TP-A0468.

A quinocycline antibiotic, kosinostatin, was isolated from the culture broth of Micromonospora sp. TP-A0468 along with isoquinocycline B. Structure of kosinostatin was determined to be the stereoisomer of isoquinocycline B regarding to the stereochemistry at the C-2' spiro carbon by NMR analysis. Kosinostatin isomerizes to isoquinocycline B through the inversion of the stereocenter at C-2'. Comparison of physico-chemical properties indicated that kosinostatin is presumably identical with quinocycline B isolated by CELMER et al. from Streptomyces aureofaciens.

Aminoglycosides↗
PubMed2002

Watasemycins A and B, new antibiotics produced by Streptomyces sp. TP-A0597.

Two novel antibiotics, watasemycins A and B, were isolated from the fermentation broth of an actinomycete strain. The producing strain TP-A0597 was isolated from the seawater sample collected in Toyama Bay, Japan and identified as Streptomyces sp. based on the taxonomic study. The new antibiotics were obtained by solvent extraction and chromatographic purification and spectroscopic analyses identified that they were new analogs of thiazostatins. Watasemycin possesses a methyl group at 5'-position of thiazostatin instead of a hydrogen atom. Watasemycins showed antibiotic activity against Gram-positive and negative bacteria and yeast.

Anti-Bacterial Agents↗
PubMed2002

Effects of hibarimicins and hibarimicin-related compounds produced by Microbispora on v-Src kinase activity and growth and differentiation of human myeloid leukemia HL-60 cells.

We studied the effects of hibarimicins and hibarimicin-related compounds produced by Microbispora rosea subsp. hibaria [glycosides (hibarimicins A, B, C, D, E, G, H and I) and aglycon (hibarimicinone)] or compounds produced by its mutants [glycosides (HMP-P4 and -Y6), aglycons (HMP-P1 and -Y1) and shunt products (HMP-M1, M2, M3 and -M4)] on v-Src tyrosine kinase and growth and differentiation of human myeloid leukemia HL-60 cells. Among them, hibarimicin B was a strong and the most selective v-Src kinase inhibitor with differentiation inducing activity of HL-60 cells. Hibarimicin E similarly induced HL-60 cell differentiation but had no v-Src kinase inhibitory activity. Hibarimicinone was the most potent v-Src kinase inhibitor, although less selective, and did not induce differentiation of HL-60 cells. Hibarimicin B competitively inhibited ATP binding to the v-Src kinase, but hibarimicinone showed noncompetitive inhibition. These two compounds, however, showed similar mixed types of inhibition against a Src substrate binding to the v-Src kinase. Altogether, these results suggest that signaling molecules other than Src might be more important in the differentiation induction of HL-60 cells.

Actinomycetales↗
PubMed2002

Anicequol, a novel inhibitor for anchorage-independent growth of tumor cells from Penicillium aurantiogriseum Dierckx TP-F0213.

A novel inhibitor for anchorage-independent growth of tumor cells was isolated from the culture broth of a fungal strain. The producing strain TP-F0213 was identified as Penicillium aurantiogriseum Dierckx based on the taxonomic study. The compound designated anicequol was obtained by solvent extraction, HP-20 and silica gel chromatographies and recrystallization. The planar structure was elucidated by NMR analysis to be 16-acetoxy-3,7,11-trihydroxyergost-22-en-6-one. The absolute configuration was determined by the X-ray analysis of 3,7-bis-p-bromobenzoyl derivative. The carbon skeleton of anicequol has the same absolute configuration as ergostane and the configurations of substituents are 3beta, 5alpha, 7beta, 11beta, 16beta and 24S. Anicequol inhibited the anchorage-independent growth of human colon cancer DLD-1 cells with the IC50 of 1.2 microM whereas the IC50 against anchorage-dependent growth was 40 microM.

Antibiotics, Antineoplastic↗