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61.
Pramod B. Shinde Ah Reum Han Jaeyong Cho So Ra Lee Yeon Hee Ban Young Ji Yoo Eun Ji Kim Eunji Kim Myoung-Chong Song Je Won Park Dong Gun Lee Yeo Joon Yoon 《Journal of biotechnology》2013
Expression plasmids carrying different deoxysugar biosynthetic gene cassettes and the gene encoding a substrate-flexible glycosyltransferase DesVII were constructed and introduced into Streptomyces venezuelae YJ003 mutant strain bearing a deletion of a desosamine biosynthetic (des) gene cluster. The resulting recombinants produced macrolide antibiotic YC-17 analogs possessing unnatural sugars replacing native d-desosamine. These metabolites were isolated and further purified using chromatographic techniques and their structures were determined as d-quinovosyl-10-deoxymethynolide, l-rhamnosyl-10-deoxymethynolide, l-olivosyl-10-deoxymethynolide, and d-boivinosyl-10-deoxymethynolide on the basis of 1D and 2D NMR and MS analyses and the stereochemistry of sugars was confirmed using coupling constant values and NOE correlations. Their antibacterial activities were evaluated in vitro against erythromycin-susceptible and -resistant Enterococcus faecium and Staphylococcus aureus. Substitution with l-rhamnose displayed better antibacterial activity than parent compound YC-17 containing native sugar d-desosamine. The present study on relationships between chemical structures and antibacterial activities could be useful in generation of novel advanced antibiotics utilizing combinatorial biosynthesis approach. 相似文献
62.
Won-Heong Lee Jin-Woo Kim Eun-Hee Park Nam Soo Han Myoung-Dong Kim Jin-Ho Seo 《Applied microbiology and biotechnology》2013,97(4):1561-1569
Sufficient supply of NADPH is one of the most important factors affecting the productivity of biotransformation processes. In this study, construction of an efficient NADPH-regenerating system was attempted using direct phosphorylation of NADH by NADH kinase (Pos5p) from Saccharomyces cerevisiae for producing guanosine diphosphate (GDP)-l-fucose and ε-caprolactone in recombinant Escherichia coli. Expression of Pos5p in a fed-batch culture of recombinant E. coli producing GDP-l-fucose resulted in a maximum GDP-l-fucose concentration of 291.5 mg/l, which corresponded to a 51 % enhancement compared with the control strain. In a fed-batch Baeyer–Villiger (BV) oxidation of cyclohexanone using recombinant E. coli expressing Pos5p, a maximum ε-caprolactone concentration of 21.6 g/l was obtained, which corresponded to a 96 % enhancement compared with the control strain. Such an increase might be due to the enhanced availability of NADPH in recombinant E. coli expressing Pos5p. These results suggested that efficient regeneration of NADPH was possible by functional expression of Pos5p in recombinant E. coli, which can be applied to other NADPH-dependent biotransformation processes in E. coli. 相似文献
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Seong Rim Byeon Hyunjin Vincent Kim Mijin Jeon Young Gil Ahn Maeng Sup Kim Jae Yang Kong Hye Yun Kim Young Soo Kim Dong Jin Kim 《Bioorganic & medicinal chemistry letters》2013,23(11):3467-3469
Alzheimer’s disease drug discovery regarding exploration into the molecules and processes has focused on the intrinsic causes of the brain disorder correlated with the accumulation of amyloid-β. An anti-amyloidogenic bis-styrylbenzene derivative, KMS80013, showed excellent oral bioavailability (F = 46.2%), facilitated brain penetration (26%, iv) in mouse and target specific in vivo efficacy in acute AD mouse model attenuating the cognitive deficiency in Y-maze test. Acute toxicity (LD50 >2000 mg/kg) and hERG channel inhibition (14% at 10 μM) results indicated safety of KMS80013. 相似文献
66.
Jeong Ah Hwang Mun Kyung Hwang Yongwoo Jang Eun Jung Lee Jong-Eun Kim Mi Hyun Oh Dong Joo Shin Semi Lim Geun og Ji Uhtaek Oh Ann M. Bode Zigang Dong Ki Won Lee Hyong Joo Lee 《The Journal of nutritional biochemistry》2013,24(6):1096-1104
Abnormal regulation of Ca2+ mediates tumorigenesis and Ca2+ channels are reportedly deregulated in cancers, indicating that regulating Ca2+ signaling in cancer cells is considered as a promising strategy to treat cancer. However, little is known regarding the mechanism by which Ca2+ affects cancer cell death. Here, we show that 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol (20-GPPD), a metabolite of ginseng saponin, causes apoptosis of colon cancer cells through the induction of cytoplasmic Ca2+. 20-GPPD decreased cell viability, increased annexin V-positive early apoptosis and induced sub-G1 accumulation and nuclear condensation of CT-26 murine colon cancer cells. Although 20-GPPD-induced activation of AMP-activated protein kinase (AMPK) played a key role in the apoptotic death of CT-26 cells, LKB1, a well-known upstream kinase of AMPK, was not involved in this activation. To identify the upstream target of 20-GPPD for activating AMPK, we examined the effect of Ca2+ on apoptosis of CT-26 cells. A calcium chelator recovered 20-GPPD-induced AMPK phosphorylation and CT-26 cell death. Confocal microscopy showed that 20-GPPD increased Ca2+ entry into CT-26 cells, whereas a transient receptor potential canonical (TRPC) blocker suppressed Ca2+ entry. When cells were treated with a TRPC blocker plus an endoplasmic reticulum (ER) calcium blocker, 20-GPPD-induced calcium influx was completely inhibited, suggesting that the ER calcium store, as well as TRPC, was involved. In vivo mouse CT-26 allografts showed that 20-GPPD significantly suppressed tumor growth, volume and weight in a dose-dependent manner. Collectively, 20-GPPD exerts potent anticarcinogenic effects on colon carcinogenesis by increasing Ca2+ influx, mainly through TRPC channels, and by targeting AMPK. 相似文献
67.
Hyunji Lee Hyeon-Son Choi Yooheon Park Chang Won Ahn Sung Ug Jung Soo Hyun Park 《Bioscience, biotechnology, and biochemistry》2013,77(10):1703-1709
Deer bone extract has the potential to relieve the discomfort or the articular cartilaginous damage associated with osteoarthritic (OA) and may be useful as a natural supplement for OA treatment without serious side effects. We analyzed the expression of pro-inflammatory cytokine and cartilage-related genes in monosodium iodoacetate-induced OA rats. Increases in the levels of serum pro-inflammatory cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly inhibited by the administration of deer bone extract (p?<?0.05). Decreases in the expression of collagen type II (COL2) and tissue inhibitors of metalloproteinases (TIMPs) mRNAs in the cartilage were significantly inhibited by deer bone extract treatment (p?<?0.05). The deer bone extract significantly suppressed the expression of matrix metalloproteinases (MMPs) mRNAs in the cartilage. The deer bone extract induced the up-regulation of COL2 and TIMP mRNAs and the down-regulation of MMP mRNAs by suppressing the expression of pro-inflammatory cytokine mRNAs. 相似文献
68.
Seongho Jang Eu Ddeum Park Hyung Joo Suh Sang Hun Lee Jin Soo Kim 《Bioscience, biotechnology, and biochemistry》2013,77(10):1716-1722
To investigate the activity of fermented deer antler on exercise endurance capacity, we evaluated endurance capacity in five-week-old male BALB/c mice by administering the fermented deer antler extract (FA) or the non-fermented deer antler extract (NFA) and then subjected the mice to exercise in the form of swimming. The mice administered 500?mg/kg/day of FA showed a significant increase in swimming time compared with mice administered placebo (16.55?min vs. 21.64?min, P?<?0.05). Serum lactate dehydrogenase (LDH), the marker of the liver and muscle damage, was significantly lower in FA groups. However, NFA groups did not show significantly different swimming time or serum LDH from that of the control group. Moreover, the FA-500 group had significantly higher hepatic superoxide dismutase (SOD) activity after forced swimming than the control and NFA groups (P?<?0.05). These findings suggest that fermentation may increase the exercise endurance capacity of the deer antler. 相似文献
69.
Piperlonguminine (PL), an important component of Piper longum fruits, is known to exhibit anti-hyperlipidemic, antiplatelet and anti-melanogenic activities. Here, the anticoagulant activities of PL were examined by monitoring activatedpartial-thromboplastin-time (aPTT), prothrombin-time (PT), and the activities of thrombin and activated factor X (FXa). The effects of PL on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were also tested in tumor necrosis factor-α (TNF-α) activated HUVECs. The results showed that PL prolonged aPTT and PT significantly and inhibited the activities of thrombin and FXa. PL inhibited the generation of thrombin and FXa in HUVECs. In accordance with these anticoagulant activities, PL prolonged in vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by PL. Collectively, our results suggest that PL possesses antithrombotic activities and that the current study could provide bases for the development of new anticoagulant agents. [BMB Reports 2013; 46(10): 484-489] 相似文献
70.
Adhesion molecules such as ICAM-1 are important in the infiltration of leukocytes into the site of inflammation. In this study, we investigated the inhibitory effects of curcumin on ICAM-1 expression and monocyte adhesiveness as well as its underlying action mechanism in the TNF-α-stimulated keratinocytes. Curcumin induced expression of heme oxygenase-1 (HO-1) in the human keratinocyte cell line HaCaT. In addition, curcumin induced Nrf2 activation in dose- and time-dependent manners in the HaCaT cells. Curcumin suppressed TNF-α- induced ICAM-1 expression and subsequent monocyte adhesion, which were reversed by the addition of tin protoporphyrin IX (SnPP), a specific inhibitor of HO-1, or HO-1 knockdown using siRNA. Furthermore, Nrf2 knockdown using siRNA reversed the inhibitory effect of curcumin on the TNF-α-induced ICAM-1 expression and adhesion of monocytes to keratinocytes. These results suggest that curcumin may exert its anti-inflammatory activity by suppressing the TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion via expression of HO-1 in the keratinocytes. [BMB Reports 2013;46(8): 410-415] 相似文献