• BMB Reports
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• v.50 no.6
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• pp.329-334
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• 2017

Protein tyrosine phosphatases (PTPs) play crucial roles in signal transduction and their functional alteration has been detected in many diseases. PTP inhibitors have been developed as therapeutic drugs for diseases that are related to the activity of PTPs. In this study, PTP inhibitor XIX, an inhibitor of CD45 and PTEN, was investigated whether it inhibits other PTPs. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) was selectively inhibited by the inhibitor in a competitive manner. Drug affinity responsive target stability (DARTS) analysis showed that the inhibitor induces conformational changes in PTPN2. Phosphorylation levels of signal transducer and activator of transcription 3 (STAT3) at Tyr-705, a crucial site for STAT3 activation and target site of PTPN2, decreased upon exposure to the inhibitor. Our results suggest that PTP inhibitor XIX might be considered as an effective regulator of PTPN2 for treating diseases related to PTPN2.

• Journal of Life Science
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• v.9 no.2
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• pp.5-8
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• 1999

We isolated a sphingonyelinase (SMase) inhibitor, which would be a potential reagent to regulate cell proliferation, oncogenesis, and inflammation, from a strain of Streptomyces sp.. In this paper, we report the optimal conditions for the production of SMase inhibitor, designed as sphinin, from Streptomyces sp. F50970. The optimal carbon and nitrogen source were 1% soluble starch and 0.05%-0.15% trypton. Most of monosaccharides and high concentration of soluble starch above 1.0% caused falling of pH and sphinin production. Zn2+, Cu2+, Fe2+, Mn2+, and Co2+inhibited cell growth and the production of sphinin. Inorganic phosphate promoted the sphinin production. Optimal initial pH for the production of sphinin was 7.5-8.0. Addition of CaCO3 to the medium resulted in an increase of inhibitor production. Based on these results, we designed a fermentation medium for the production of a SMase inhibitor, sphinin, from Streptomyces sp. F50970.

• Journal of Microbiology and Biotechnology
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• v.24 no.5
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• pp.667-674
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• 2014

Twenty-five Saccharomyces cerevisiae strains were screened for the highest sugar tolerance, ethanol-tolerance, ethanol production, and inhibitor resistance, and S. cerevisiae KL5 was selected as the best strain. Inhibitor cocktail (100%) was composed of 75 mM formic acid, 75 mM acetic acid, 30 mM furfural, 30 mM hydroxymethyl furfural (HMF), and 2.7 mM vanillin. The cells of strain KL5 were treated with ${\gamma}$-irradiation, and among the survivals, KL5-G2 with improved inhibitor resistance and the highest ethanol yield in the presence of inhibitor cocktail was selected. The KL5-G2 strain was adapted to inhibitor cocktail by sequential transfer of cultures to a minimal YNB medium containing increasing concentrations of inhibitor cocktail. After 10 times of adaptation, most of the isolated colonies could grow in YNB with 80% inhibitor cocktail, whereas the parental KL5 strain could not grow at all. Among the various adapted strains, the best strain (KL5-G2-A9) producing the highest ethanol yield in the presence of inhibitor cocktail was selected. In a complex YP medium containing 60% inhibitor cocktail and 5% glucose, the theoretical yield and productivity (at 48 h) of KL5-G2-A9 were 81.3% and 0.304 g/l/h, respectively, whereas those of KL5 were 20.8% and 0.072 g/l/h, respectively. KL5-G2-A9 reduced the concentrations of HMF, furfural, and vanillin in the medium in much faster rates than KL5.

• Microbiology and Biotechnology Letters
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• v.24 no.2
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• pp.227-233
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• 1996

Tyrosinase is an enzyme which catalyzes an enzymatic browning of some foods and in vivo synthesis of melanin. In order to produce natural and edible inhibitor of the enzyme which is expected to have whitening effect on melanogenesis, a microorganism was selected from fermented foods. It was named as NU-7, and cultured in mushroom (Lentinus edodes, Shiitake) media. Optimal media to produce tyrosinase inhibitor was formulated by varing nitrogen or carbon content. If glucose content was in a range of 3-20% and ammonium sulfate was in a range of 0-0.25%, production of inhibitor was independent of cell mass. Addition of ammonium sulfate as a nitrogen source had little effect on inhibitor production. Production of inhibitor (Y) was proportionally related to shiitake content (X) with a regression equation of Y= -0.96X$^{2}$ + 13.07X + 14.43 (R = 0.96). These results indicate that shiitake and glucose are necessary for the production of tyrosinase inhibitor. In the analysis of mycotoxin in culture broth, aflatoxin was not detected, suggesting that it would be probably edible.

• Journal of Life Science
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• v.6 no.2
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• pp.120-128
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• 1996

In the screening of actinomycetes culture filtrate for inhibitor of adenosine deaminase, a novel inhibitor was found in a cultured broth of strain J-144K. The optimum conditions for the adenosine deaminase inhibitor production from the isolated strain J-144K were evaluated. This strain showed the maximum yield of adenosine deaminase inhibitor when grown at pH 7.0 and 30$\circ$C for 60 hours in the medium of 1.0% dextrose, 0.5% yeast extract, 0.5% peptone and 0.1% KH$_{2}$PO$_{4}$ under the aerobic condition. Through the activated charcoal extraction, methanol fractionation, Dowex 50 H$^{+}$ X-8 ion exchange column chromatography, Dowex CI$^{-}$ X-8 ion exchange column chromatography, and Sephadex G-15 gel filtration procedures, this inhibitor was purified with three materials.

• Journal of Microbiology and Biotechnology
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• v.12 no.6
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• pp.895-900
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• 2002

A soil microorganism producing ${\alpha}$- and ${\beta}$-glucosidase inhibitors was identified as Bacillus lentimorbus, based on the fatty acid and morphological analyses, along with biochemical and physiological tests. The ${\alpha}$-glucosidase inhibitor was highly produced by this strain in a culture medium containing $0.25\%$ of sodium glutamate and $0.5\%$ of glucose, pH 8.0 at $30^{\circ}C$ for 2 days. The ${\alpha}$-glucosidase inhibitor from culture filtrate of his strain was identified as water soluble, organic solvent nonextractable, and heat stable. In addition to ${\alpha}$-glucosidase inhibitor, this strain also produced ${\beta}$-glucosidase inhibitor in he same culture medium and this inhibitor showed an antifugal activity against Botrytis cinerea. While the production of ${\alpha}$- glucosidase inhibitor was decreased by a glucose concentration higher than $1\%$, the production of ${\beta}$-glucosidase inhibitor was lot Influenced by a glucose concentration higher than $20\%$. The ${\alpha}$-glucosidase inhibitor from culture filtrate of this strain was separated from the ${\beta}$-glucosidase inhibitor through Sephadex G-100 column chromatography.

• Mycobiology
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• v.36 no.2
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• pp.102-105
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• 2008

The acetylcholinesterase (AChE) inhibitor of Yarrowia lipolytica S-3 was maximally produced when it was incubated at $30^{\circ}C$ for 36 h in an optimal medium containing 1% yeast extract, 2% peptone and 2% glucose, with an initial pH 6.0. The final AChE inhibitory activity under these conditions was an $IC_{50}$ value of 64mg/ml. After partial purification of the AChE inhibitor by means of systematic solvent extraction, the final $IC_{50}$ value of the partially purified AChE inhibitor was 0.75 mg/ml. We prepared a test product by using the partially purified AChE inhibitor and then determined its stability for the development of a new antidementia commercial product. The test product was stable at room temperature for 15 weeks.

• Journal of Life Science
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• v.26 no.7
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• pp.826-834
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• 2016

The present investigation was undertaken to examine the effectiveness of the combination treatment of an Hsp90 inhibitor and a SIRT1 inhibitor on suppressing the growth of chemo-resistant human cancer cells. We showed that inhibition of SIRT1 effectively potentiated the cytotoxicity of 17-allylamino-17-demethoxygeldanamycin (17-AAG) and reversed Hsp90 inhibitor resistance in multidrug-resistant (MDR) human ovarian HeyA8-MDR cells. Amurensin G, a potent natural SIRT1 inhibitor, enhanced Hsp90 inhibitor-mediated abrogation of the Hsp90 chaperone function and accelerated degradation of mutated p53 (mut p53), an Hsp90 client protein, by up-regulation of ubiquitin ligase CHIP. Knock-down of CHIP significantly attenuated amurensin G-induced mut p53 degradation. Down-regulation of mut p53 reduced the expression of heat shock factor1 (HSF1)/heat shock proteins (Hsps), a major cause of Hsp90 inhibitor resistance, which led to sensitization of the MDR cells to the Hsp90 inhibitor by the SIRT1 inhibitor. Amurensin G potentiated cytotoxicity of the Hsp90 inhibitor in HeyA8-MDR cells through suppression of 17-AAG-induced Hsp70 and Hsp27 induction via down-regulation of mut p53/HSF1, and it caused activation of PARP and inhibition of Bcl-2. Our data suggests that SIRT1 inhibitors could be used to sensitize MDR cells to Hsp90 inhibitors, possibly through suppression of the mut p53/HSF1-dependent pathway, and a novel mut p53-directed action of SIRT1 inhibition could effectively prevent mut p53 accumulation in MDR cells.

• Biomedical Science Letters
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• v.18 no.3
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• pp.307-309
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• 2012

(S)-(+)-3(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo3,4-dihydro-2H,8H-pyrano[3,2-g]Chromen-3-yl-ester (Compound 6, C6) is synthesized from (S)-(+)-decursin and attenuates the pathophysiologic progression of asthma in a ovalbumin-induced asthmatic mouse model. In the present study, we examined the effect of C6 on spontaneous apoptosis of eosinophils and neutrophils of normal and asthmatic subjects. C6 increased the apoptosis of asthmatic eosinophils in a dose-dependent manner, but it inhibited neutrophil apoptosis. C6 has no effect on apoptosis of normal eosinophils and neutrophils. LY294002, an inhibitor of PI3K, rottlerin, an inhibitor of $PKC{\delta}$, Ro-31-8425, an inhibitor of classical PKC inhibitor, PD98059, an inhibitor of MEK, and BAY 11-7085, an inhibitor of NF-${\kappa}B$, blocked the inhibitory effect on apoptosis of asthmatic neutrophils due to C6. These results indicate that C6 may be valuable as a therapeutic agent for the treatment of asthma.

• Microbiology and Biotechnology Letters
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• v.27 no.6
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• pp.458-465
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• 1999

Streptomyces luteogriseus KT-10 isolated from Korean farm soil produced a strong cathepsin B inhibitor. Optimal conditions for the cathepsin B inhibitor production by s. luteogriseus KT-10 were evaluated. The cathepsin B inhibitor was produced with maximal yield in the cultural condition of pH 7.0 and $25^{\circ}C$ for 4 days. Optimal medium for the cathepsin B inhibitor production was determined to be a medium containing 20g, peptone 3g, yeast extract 1g, K2HPO4 0.5g, MgSO4.7H2O 0.5g, NaNO3 0.5g, NaCl 0.5g per l. The cathepsin B inhibitor produced by S. luteogriseus KT-10 could also inhibit the other proteinases such as trypsin, papain, and cathepsin D.