• Title/Summary/Keyword: Co-metabolites

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Selective Production of Epothilone B by Heterologous Expression of Propionyl-CoA Synthetase in Sorangium cellulosum

  • Han, Se-Jong;Park, Sang-Woo;Kim, Byung-Woo;Sim, Sang-Jun
    • Journal of Microbiology and Biotechnology
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    • v.18 no.1
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    • pp.135-137
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    • 2008
  • The metabolic engineering of epothilones, as secondary metabolites, was investigated using Sorangium cellulosum to achieve the selective production of epothilone B, a potent anticancer agent. Thus, the propionyl-CoA synthetase gene (prpE) from Ralstonia solanacearum was heterologously expressed in S. cellulosum to increase the production of epothilone B. Propionyl-CoA synthetase converts propionate into propionyl-CoA, a potent precursor of epothilone B. The recombinant S. celluloslim containing the prpE gene exhibited a significant increase in the resolution of epothilones B/A, with an epothilone B to A ratio of 127 to 1, which was 100 times higher than that of the wild-type cells, demonstrating its potential use for the selective production of epothilone B.

Drug Interaction of Cimetidine and Cyclosporine in Human (정상지원자에서 Cimetidine과 Cyclosporine의 약물상호작용)

  • Choi, In;Choi, Jun Shik
    • Korean Journal of Clinical Pharmacy
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    • v.7 no.2
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    • pp.51-63
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    • 1997
  • The effect of cimetidine administration on the pharmacokinetic parameters of cyclosporine were determined in healthy voluteers. This study was performed in 10 volunteers of age ranged 22-48 years and body weight 48-62 kg. This study was performed with cross-over design. Mono cyclosporine and cyclosporine metabolites was extracted from whole blood analysed by fluororescence polarization immune assay (TDX-FLX, Abbott). After coadministration of cimetidine (300 mg) with cyclosporine (300 mg) orally, maximum concentration of mono cyclosporine was significantly increased $1221{\pm}143\;ng/ml\;to\;1562{\pm}184\;ng/ml$ (P<0.05), area under the time curve of cyclosporine (12 hr) also was significantly increased $7478{\pm}829\;ng/ml{\cdot}hr\;to\;9721{\pm}879\;ng/ml{\cdot}hr$ (P<0.05) and absolute baioavailability of cyclosporine was increased $50\pm5.6\%\;to\;57.6\pm6.1\%\;(P<0.05)$ compared to control group. The blood concentrations of cyclopsorine metabolites were significantly decrased (P<0.05) after coadministration of cimetidine. In cimetidine pretreated group, blood mono cyclosporine concentrations were increased significan시y $1220.0\pm203.00\;ng/ml\;to\;1510.0\pm204.00\;ng/ml$ compared with control group (P<0.05). In the mono cyclosporine pharmacokinetic parameter after oral administration absorption rate and maximum concentration were significantly higher in cimetidine coadministered and pretreated group than control group (P<0.05). The ratio of metabolites and mono cyclosporine concentrations was decreased significantly from $70.8\%\;in\;control\;to\;34.8\%$ in coadministration of cimetidine orally. As matter of facts these reults are considered to inhibition of cyclosporine hepatic metabolism and increasing of cyclosporine absorption rate in gastrointestinal tract because of maintaining cyclosporine stability in elevated gastric pH by cimetidine. We considered, it appeares that cimetidine increase bioavailability of cyclosporine by increasing oral absorption and by decreasing hepatic clearance. But the absorption and clearance of cyclosporine was highly variable individually, and therefore we consider that cyclosporine blood level monitoring would be essential in patients with cimetidine co-administration.

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Biosynthesis of $17\alpha-hydroxy$, $20\alpha-dihydroprogesterone$ by Ovaries of the Spotted Flounder (Verasper variegatus)

  • Baek Hea-Ja
    • Fisheries and Aquatic Sciences
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    • v.4 no.2
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    • pp.70-74
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    • 2001
  • To examine the production of steroids with potential oocyte maturation-inducing activity in the spotted flounder, Verasper variegatus, we have incubated post-vitellogenic oocytes (0.82­0.95mm in diameters) with radiolabeled pregnenolone and $17\alpha-hydroxyprogesterone$. The resulting metabolites were analyzed by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The two main metabolites (progestogens) found in both incubations co-migrated with $17\alpha-hydroxy$, $20\alpha-dihydroprogesterone$ $(17\alpha, 20\alpha OHP)$ and $17\alpha-hydroxy,\;$20\beta-dihydroprogesterone$ (17 a20{30HP). Additional chromatography by HPLC and TLC confirmed the presence of radioactive $17\alpha, 20\alpha OHP$ and a large amount of unknown metabolite. The present study did not reveal in vitro formation of $l7\alpha 20\beta OHP$. Although 1$l7\alpha 20\beta OHP$ was found in a small amount, the synthesis of this steroid suggests that it may play a role in regulating the oocyte maturation process in the spotted flounder.

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Changes in Metabolites and Embryo Growth during Seeds Priming in Tobacco

  • Min, Tai-Gi;Seou, Byung-Moon;Lee, Suk-Soon
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.44 no.3
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    • pp.273-276
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    • 1999
  • Some metabolites and embryo growth of primed tobacco (Nicotiana tabacum L. cv. ‘KFI09’) seeds were observed during priming. The seeds were primed at 15 and $25^{\circ}C$ for 1, 2, 3, 5, 10 and 15 days in a -0.8 MPa polyethylene glycol 6000 (PEG) solution. The time to 50% seed germination (T$_{50}$) was greatly reduced when the seeds were primed at $25^{\circ}C$ when compared with 15$^{\circ}C$. The $\alpha$-amylase activity and sugars and amino acid contents in the seeds primed at $25^{\circ}C$ greatly increased, while $\alpha$-amylase activity was similar, and sugar and amino acid contents increased slightly in the seeds primed at 15$^{\circ}C$. When the seeds were primed at $25^{\circ}C$, growth of the embryo which was enclosed by endosperm was detected, while the endosperm became thinner as the priming duration was extended.d.

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Effect of Carbon Monoxide Intoxication on the Change in Contents of Cerebral Energy Metabolites of Rats (흰쥐에서의 일산화탄소(一酸化炭素) 중독(中毒)이 뇌(腦)에너지 대사(代謝) 관련물질(關聯物質) 함량변화(含量變化)에 미치는 영향)

  • Yun, Jae-Soon;Choi, Shin-Kyu
    • YAKHAK HOEJI
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    • v.33 no.3
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    • pp.149-155
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    • 1989
  • To predict the influence of carbon monoxide poisonining on cerebral energy metabolism, rats were exposed to 5000 ppm environment for 30 minutes. Carboxyhemoglobin (HBCO) saturation rate in this condition was 72% equally in male and female rats. Cerebral cortex in the rats showed lower level of ATP, glucose, creatine phosphate and higher level of lactate, pyruvate by anaerobic glycolysis. As for the levels of ATP, creatine phsphate and glucose, the cerebral cortex contents of them were larger in female rats of estrus than in male rats, whereas there was no difference between sexes in the levels of pyruvate and lactate. According to time passage from CO intoxication, the mode of changes in cerebral energy metabolite contents was similar in both sexes.

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Screening of Myxobacteria Carrying Tubulysin Biosynthetic Genes

  • Hyun, Hyesook;Choi, Juo;Kang, Daun;Kim, Yungpil;Lee, Pilgoo;Chung, Gregory J.Y.;Cho, Kyungyun
    • Microbiology and Biotechnology Letters
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    • v.49 no.1
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    • pp.32-38
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    • 2021
  • Tubulysins are a group of secondary metabolites produced by myxobacteria that inhibit the function of the eukayotic cytoskeleton. We developed a pair of PCR primers that specifically amplified tubulysin biosynthetic genes. Using these primers, eight out of the eighty-one strains of myxobacteria belonging to the Cystobacteraceae family that harbored putative tubulysin biosynthetic genes were screened through PCR analysis. The selected strains included two Archangium gephyra, two Stigmatella sp., two Vitiosangium cumulatum, and two unidentified myxobacteria. LC-MS analysis of the culture extracts from the selected strains revealed that A. gephyra KYC4066 produced putative tubulysin A and B.

Statistical Optimization of Culture Conditions for the Production of Aphicidal Metabolites of Beauveria bassiana Bb08 (Beauveria bassiana Bb08의 살충성 물질 생산을 위한 배양조건의 통계적 최적화)

  • Go, Eunsu;Lim, Younghoon;Jeong, Hyeongchul;Choi, Jaepil;Park, Inseo;Kim, Jeong Jun;Lee, Dong-Jin;Kim, Keun
    • Microbiology and Biotechnology Letters
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    • v.41 no.4
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    • pp.398-406
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    • 2013
  • For the maximal production of aphicidal metabolites produced by the Beauveria bassiana Bb08, statistical methods such as the Box-Behnken experimental design and response surface methodology were used. The fungal culture filtrate was sprayed towards 3-star aphids and the mortality was examined. After the statistical analysis of the aphid mortality, the optimal culture conditions were found to be a culture temperature of $26.2^{\circ}C$, medium pH 5.9, flask shaking speed of 209.0 rpm, and culture time of 5.9 days. The expected mortality on days 4, 5, and 6 after spraying the filtrate on to the aphids were 76.8%, 84.9%, and 89.4%, respectively. All 4 factors of the culture conditions significantly affected the production of the aphicidal metabolites, and the order of significance was temperature, pH, culture time and shaking speed.

Varying Inocula Permutations (Aspergillus oryzae and Bacillus amyloliquefaciens) affect Enzyme Activities and Metabolite Levels in Koji

  • Gil, Hye Jeong;Lee, Sunmin;Singh, Digar;Lee, Choong Hwan
    • Journal of Microbiology and Biotechnology
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    • v.28 no.12
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    • pp.1971-1981
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    • 2018
  • In this study, we investigated the altered enzymatic activities and metabolite profiles of koji fermented using varying permutations of Aspergillus oryzae and/or Bacillus amyloliquefaciens. Notably, the protease and ${\beta}$-glucosidase activities were manifold increased in co-inoculated (CO) koji samples (co-inoculation of A. oryzae and B. amyloliquefaciens). Furthermore, gas chromatography-mass spectrometry (GC-MS)-based metabolite profiling indicates that levels of amino acids, organic acids, sugars, sugar alcohols, fatty acids, nucleosides, and vitamins were distinctly higher in CO, SA (sequential inoculation of A. oryzae, followed by B. amyloliquefaciens), and SB (sequential inoculation of B. amyloliquefaciens, followed by A. oryzae). The multivariate principal component analysis (PCA) plot based on GC-MS datasets indicated a clustered pattern for MA and MB (koji samples inoculated either with A. oryzae or B. amyloliquefaciens) across PC2 (20.0%). In contrast, the CO, SA, and SB metabolite profiles displayed segregated patterns across PLS1 (22.2%) and PLS2 (21.1%) in the partial least-square discriminant analysis (PLS-DA) model. Intriguingly, the observed disparity in the levels of primary metabolites was engendered largely by higher relative levels of sugars and sugar alcohols in MA, SA, and CO koji samples, which was commensurate with the relative amylase activities in respective samples. Collectively, the present study emphasizes the utility of integrated biochemical and metabolomic approaches for achieving the optimal permutation of fermentative inocula for industrial koji preparation.

Functional Implications of HMG-CoA Reductase Inhibition on Glucose Metabolism

  • Han, Ki Hoon
    • Korean Circulation Journal
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    • v.48 no.11
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    • pp.951-963
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    • 2018
  • HMG-CoA reductase inhibitors, i.e. statins, are effective in reducing cardiovascular disease events but also in cardiac-related and overall mortality. Statins are in general well-tolerated, but currently the concerns are raised if statins may increase the risk of new-onset diabetes mellitus (NOD). In this review, the possible effects of statins on organs/tissues being involved in glucose metabolism, i.e. liver, pancreas, adipose tissue, and muscles, had been discussed. The net outcome seems to be inconsistent and often contradictory, which may be largely affected by in vitro experimental settings or/and in vivo animal conditions. The majority of studies point out statin-induced changes of regulations of isoprenoid metabolites and cellassociated cholesterol contents as predisposing factors related to the statin-induced NOD. On the other hand, it should be considered that dysfunctions of isoprenoid pathway and mitochondrial ATP production and the cholesterol homeostasis are already developed under (pre)diabetic and hypercholesterolemic conditions. In order to connect the basic findings with the clinical manifestation more clearly, further research efforts are needed.

Development of Drug Candidates based on Natural Products Against COVID-19 (천연식물자원 활용 코로나19 억제 치료제 개발)

  • Se Chan Kang
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2021.04a
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    • pp.3-3
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    • 2021
  • The ongoing global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not only influenced over 1.26 billion people but also caused 2.77 million deaths worldwide (as of March 28, 2021). The vaccination could be the most efficient strategy to prevent SARS-CoV-2 infection. However, the continuous emergence of novel variants such as VUI-202012/01 (United Kingdom) and 501.V2 (South Africa) raises huge concerns about the effectiveness of the vaccine designed to target the original virus strain. Since ancient times regardless of the East and West, the plants which refered in this presentation have been consumed not only as food but also as a natural medicine to treat diverse diseases including infectious diseases. Importantly, these plants contain secondary metabolites that display antiviral activity involved in the inhibition of viral adsorption, penetration, and replication. Also, plant-derived natural medicines are expected to have a wider range of efficacy and fewer side effects than synthetic medicine, discovering novel plant-based viral agents would be a promising strategy to fight against SARS-CoV-2.

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