Keiko Furihata

Prunustatin A, a Novel GRP78 Molecular Chaperone Down- regulator Isolated from Streptomyces violaceoniger

In the course of our screening program for regulators of a molecular chaperone GRP78 expression, we isolated a novel inhibitor of GRP78 expression, designated as prunustatin A, from Streptomyces violaceoniger 4521-SVS3. The structure of prunustatin A was determined by a series of NMR analyses to be an oxidized type of the neoantimycin family. Prunustatin A inhibited the expression of GRP78 induced by 2-deoxyglucose in human fibrosarcoma HT1080 cells accompanied by global cell death without showing cytotoxicity under normal nutrient condition.

Thioviridamide, a Novel Apoptosis Inducer in Transformed Cells from Streptomyces olivoviridis

In the course of screening for antitumor antibiotics using 3Y1 rat fibroblasts transformed with adenovirus oncogenes, a new active substance designated thioviridamide was isolated from the culture broth of an actinomycete. The producing organism was identified as Streptomyces olivoviridis on the basis of its culture characteristics and physiological properties. Thioviridamide showed cytotoxicity selectively against Ad12-3Y1 cells (IC50=3.9 ng/ml) and E1A-3Y1 cells (IC50=32 ng/ml), both of which contain the adenovirus E1A oncogene. Significant numbers of Ad12-3Y1 cells treated with thioviridamide contained condensed chromatin and fragmented nuclei, indicating that thioviridamide induced apoptosis.

Isolation and Characterization of 2-Nitroimidazole Produced by Streptomyces Species as an Inhibitor of Both Carbonic Anhydrase and Shell Formation in the Barnacle Balanus amphitrite

Abstract: Carbonic anhydrase is thought to be involved in the process of calcium carbonate deposition in calcified tissues of many organisms. Barnacles form hard calcified shells for protection against predation, and represent a class of marine-fouling animals. In order to inhibit barnacle growth by inhibiting shell formation, we searched for carbonic anhydrase inhibitors from microbial secondary metabolites. A simple assay for assessing carbonic-anhydrase-inhibiting activity was developed. Screening of many microorganisms isolated from soil with this assay resulted in a microbial strain that produced a carbonic anhydrase inhibitor. This strain was identified as Streptomyces eurocidicus mf294. The inhibitor was isolated through 4 purification steps and identified as 2-nitroimidazole on the basis of spectroscopic data. 2-Nitroimidazole inhibited barnacle carbonic anhydrase dose-dependently and complete inhibition was reached at the concentration of 1 × 10−5 M. 2-Nitroimidazole did not affect settlement or metamorphosis of barnacle larvae, but inhibited shell formation at concentrations higher than 1 × 10−4 M. These findings strongly support the idea that carbonic anhydrase is involved in calcification.

Effect of detoxin D on blasticidin S uptake inBacillus cereus

The active transport of blasticidin S into the cells ofBacillus cereus was significantly inhibited by the addition of detoxin D or poisons of energy metabolism.