簡易檢索 / 詳目顯示

研究生: 呂坤樺
Lu, Kun-Hua
論文名稱: 以c-AMP解除碳源代謝抑制於檢測不同基質中的苯乙酸及苯乙胺
Using c-AMP to Release the Carbon Catabolite Repression in Different Types of Matrices for the Determination of Phenylacetic Acid and Phenylethylamine
指導教授: 葉怡均
Yeh, Yi-Chun
學位類別: 碩士
Master
系所名稱: 化學系
Department of Chemistry
論文出版年: 2019
畢業學年度: 107
語文別: 中文
論文頁數: 94
中文關鍵詞: 全細胞生物感測器苯乙胺苯乙酸碳源代謝抑制效應解抑制模擬環腺苷酸尿液樣品
英文關鍵詞: Whole cell-based biosensor, Phenethylamine, Phenylacetic acid, Carbon catabolite repression, The simulation of release, Cyclic adenosine monophosphate, Urine sample
DOI URL: http://doi.org/10.6345/NTNU201900504
論文種類: 學術論文
相關次數: 點閱:119下載:0
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 苯乙胺及苯乙酸分別為人體中重要的神經傳導物質以及代謝產物,其中尿液中的苯乙酸為偵測苯丙酮尿症患者的重要指標。然而尿液樣品所產生的基質干擾,抑制了細胞中環腺苷酸-CRP 轉錄結合位點系統,造成全細胞生物感測器的偵測異常。在此,先在標準培養液中模擬出碳源代謝抑制效應,並透過額外添加環腺苷酸、2-脫氧葡萄糖及更換培養液氮源的方式解除其效應,再將此優化的解抑制條件運用在尿液樣品中,達到更廣的檢測應用。

    Phenylethylamine and phenylacetic acid are important metabolites in the human body. Specifcally, urinary phenylacetic acid is a vital indicator for the diagnosis of phenylketonuria. However, the matrix effect generated by the urinary glucose represses the cyclic adenosine monophosphate-CRP transcriptional binding in the cell. In this study, the carbon catabolite repression is first simulated in the standard culture media, and it is released by adding cyclic adenosine monophosphate, 2-Deoxy-D glucose, and replacing nitrogen sources of the culture media. Finally, the optimization of released conditions is applied to the urine samples to achieve a better detection application.

    目錄 中文摘要 v ABSTRACT vi 縮寫表 vii 圖目錄 viii 表目錄 xi Chapter 1 實驗概論 1 1-1 生物感測器 (Biosensor) 1 1-1-1 生物感測器的發展 2 1-1-2生物感測器的類型 4 1-1-3生物感測器的運用 5 1-2 全細胞生物感測器 (Whole cell-based biosensor) 6 1-2-1 感測器原理 7 1-2-2 全細胞感測器文獻回饋 8 1-3克隆 (Clone) 10 1-3-1 基因克隆 11 1-3-1-1 目標基因的獲得 (Insert) 12 1-3-1-2 選擇適當的載體 (Vector) 13 1-3-1-3 人工體外重組 (Ligase) 13 1-3-1-4 轉化作用 (Transform) 13 1-3-1-5 聚合酶連鎖反應 (PCR) 14 1-3-2 大腸桿菌上的基因工程 14 1-3-2-1 大腸桿菌的表達系統 15 1-4人體神經性物質苯乙胺 ( phenylethylamine) 16 1-4-1 苯乙胺的性質 17 1-4-2 苯乙胺對神經的調控 17 1-4-3 愛情巧克力理論 18 1-4-4 偵測苯乙胺 18 1-5 人體代謝物質苯乙酸 (phenylacetic acid) 18 1-5-1 苯乙酸的性質 19 1-5-2 苯乙酸在人體中的代謝 19 1-5-3 文獻中的苯乙酸感測器 20 1-6 芳香族化合物在大腸桿菌中的調控與代謝 21 1-6-1 對苯乙胺之代謝與調控 23 1-6-2 對苯乙酸之代謝與調控 25 1-6-3 苯丙酮尿症 (phenylketonuria,PKU) 26 1-7 環球調控系統 (global regulator) 27 1-7-1 CRP 結合位點 28 1-7-2 FNR 結合位點 29 1-8 碳源代謝抑制效應 (CCR) 29 1-8-1 磷酸根轉移系統 30 1-8-2 c-AMP-CRP 系統 31 1-9 實驗動機 32 Chapter 2 實驗方法與設計 34 2-1 實驗儀器 34 2-2 實驗藥品 35 2-3 克隆 (clony) 37 2-3-1 質體萃取 (plasmid extraction) 37 2-3-2 剪輯質體 (digestion) 37 2-3-3 接合 (ligation) 38 2-3-4 轉化作用 (transformation) 38 2-3-5 聚合酶連鎖反應檢查 (PCR check) 39 2-3-6 膠體製作 39 2-3-7 膠體萃取/聚合酶連鎖反應清理 (gel extraction/PCR clean up) 40 2-3-8 存菌 (bacteria store) 40 2-3-9 勝任細胞製作 (competent cell) 40 2-4 實驗方法 41 2-4-1 質體選擇與設計 41 2-4-2 養菌 45 2-4-3 稀釋 (dilute) 46 2-4-4 誘導試劑 (inducer) 添加 47 2-4-5 螢光分析定量 48 2-4-6 葡萄糖對 c-AMP-CRP 系統抑制之模擬 49 2-4-7 額外添加 c-AMP 對c-AMP-CRP 系統影響之模擬 50 2-4-8 額外添加 DDG 對c-AMP-CRP 系統影響之模擬 51 2-4-9 真實樣品 (urine) 的運用 52 2-4-10 偵測極限 (LOD) 公式 53 2-4-11 M9培養液配置方法 53 Chapter 3 實驗結果與討論 54 3-1 碳源抑制效應模擬 54 3-1-1 YCY_620 54 3-1-2 YCY_877 56 3-1-3 YCY_844 58 3-2 透過基因工程證實CRP基因的重要性 59 3-2-2 YCY_896 59 3-2-3 YCY_931 60 3-3 解抑制模擬 61 3-3-1 YCY_877 64 3-3-1-1 額外供給 c-AMP 64 3-3-1-2 額外供給 DDG 67 3-3-1-3 更換培養基質中的氮源 69 3-3-2 YCY_620 71 3-3-2-1 額外供給 c-AMP 71 3-3-2-2 額外供給DDG 72 3-3-3 YCY_844 73 3-3-3-1 額外供給 c-AMP 73 3-3-3-2 額外供給 DDG 74 3-4 尿液樣品的運用 75 3-4-1 YCY_844及YCY_620於不同條件下對苯乙酸/苯乙胺產生的螢光值 76 3-4-1-1 YCY_844 76 3-4-1-2 YCY_620 78 3-4-2 YCY_844及YCY_620於不同尿液樣品中測試實驗可信度 79 3-4-2-1 YCY_844 79 3-4-2-2 YCY_620 81 Chapter 4 結論 83 Chapter 5 參考資料 84 Chapter 6 附錄 92 6-1 使用菌種 92 6-2 使用質體 93 6-3 使用引子 94

    1.Turner, A.; Karube, I.; Wilson, G. S., Biosensors: fundamentals and applications. Oxford university press: 1987.
    2.Scheller, F.; Hintsche, R.; Pfeiffer, D.; Schubert, F.; Riedel, K.; Kindervater, R., Biosensors: fundamentals, applications and trends. Sensors and Actuators B: Chemical. 1991, 4 (1-2), 197-206.
    3.Lowe, C. R., Biosensors. Philosophical Transactions of the Royal Society of London. B, Biological Sciences. 1989, 324 (1224), 487-496.
    4.Luong, J.; Mulchandani, A.; Guilbault, G. G., Developments and applications of biosensors. Trends in Biotechnology. 1988, 6 (12), 310-316.
    5.Luka, G.; Ahmadi, A.; Najjaran, H.; Alocilja, E.; DeRosa, M.; Wolthers, K.; Malki, A.; Aziz, H.; Althani, A.; Hoorfar, M., Microfluidics integrated biosensors: A leading technology towards lab-on-a-chip and sensing applications. Sensors. 2015, 15 (12), 30011-30031.
    6.Wang, J., Electrochemical glucose biosensors. Chemical reviews. 2008, 108 (2), 814-825.
    7.Schultz, J. S., Biosensors. Scientific American. 1991, 265 (2), 64-69.
    8.Updike, S.; Hicks, G. P., The enzyme electrode. Nature. 1967, 214 (5092), 986.
    9.Eggins, B. R., Chemical sensors and biosensors. John Wiley & Sons. 2008
    10.Wang, J., Glucose biosensors: 40 years of advances and challenges. Electroanalysis: An International Journal Devoted to Fundamental and Practical Aspects of Electroanalysis. 2001, 13 (12), 983-988.
    11.Stoica, L.; Ludwig, R.; Haltrich, D.; Gorton, L., Third-generation biosensor for lactose based on newly discovered cellobiose dehydrogenase. Analytical chemistry. 2006, 78 (2), 393-398.
    12.Stone, H. A.; Stroock, A. D.; Ajdari, A., Engineering flows in small devices: microfluidics toward a lab-on-a-chip. Annu. Rev. Fluid Mech. 2004, 36, 381-411.
    13.da Silva, J. C. E.; Gonçalves, H. M., Analytical and bioanalytical applications of carbon dots. TrAC Trends in analytical chemistry. 2011, 30 (8), 1327-1336.
    14.Yayon, A.; Klagsbrun, M.; Esko, J. D.; Leder, P.; Ornitz, D. M., Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Cell. 1991, 64 (4), 841-848.
    15.Săndulescu, R.; Tertiş, M.; Cristea, C.; Bodoki, E., New materials for the construction of electrochemical biosensors. Biosensors-Micro and Nanoscale Applications. IntechOpen, 2015.
    16.Prodromidis, M. I.; Karayannis, M. I., Enzyme based amperometric biosensors for food analysis. Electroanalysis: An International Journal Devoted to Fundamental and Practical Aspects of Electroanalysis. 2002, 14 (4), 241-261.
    17.Dremel, B. A.; Schaffar, B. P.; Schmid, R. D., Determination of glucose in wine and fruit juice based on a fibre-optic glucose biosensor and flow-injection analysis. Analytica Chimica Acta. 1989, 225, 293-301.
    18.Proll, G.; Tschmelak, J.; Gauglitz, G., Fully automated biosensors for water analysis. Analytical and bioanalytical chemistry. 2005, 381 (1), 61-63.
    19.Mitchell, S.; Poulsson, A.; Davidson, M.; Emmison, N.; Shard, A.; Bradley, R. H., Cellular attachment and spatial control of cells using micro-patterned ultra-violet/ozone treatment in serum enriched media. Biomaterials. 2004, 25 (18), 4079-4086.
    20.Haron, S.; Ray, A. K., Optical biodetection of cadmium and lead ions in water. Medical engineering & physics. 2006, 28 (10), 978-981.
    21.Ziegler, C., Cell-based biosensors. Fresenius' journal of analytical chemistry. 2000, 366 (6-7), 552-559.
    22.Pancrazio, J. J.; Whelan, J.; Borkholder, D. A., Development and application of cell-based biosensors. Annals of biomedical engineering. 1999, 27 (6), 697-711.
    23.De Lorenzo, V.; Herrero, M.; Jakubzik, U.; Timmis, K. N., Mini-Tn5 transposon derivatives for insertion mutagenesis, promoter probing, and chromosomal insertion of cloned DNA in gram-negative eubacteria. Journal of bacteriology. 1990, 172 (11), 6568-6572.
    24.Prendergast, F. G.; Mann, K. G., Chemical and physical properties of aequorin and the green fluorescent protein isolated from Aequorea forskalea. Biochemistry. 1978, 17 (17), 3448-3453.
    25.Tsien, R. Y., The green fluorescent protein. 1998.
    26.Shimomura, O.; Johnson, F. H.; Saiga, Y., Extraction, purification and properties of aequorin, a bioluminescent protein from the luminous hydromedusan, Aequorea. Journal of cellular and comparative physiology. 1962, 59 (3), 223-239.
    27.Contag, C. H.; Bachmann, M. H., Advances in in vivo bioluminescence imaging of gene expression. 2002, 4 (1), 235-260.
    28.Fan, F.; Lewis, M. K.; Shultz, J. W.; Wood, K. V.; Butler, B., Luciferase biosensor. U.S. Patent No. 8,183,036. 2012.
    29.Guo, K. H.; Chen, P. H.; Lin, C.; Chen, C. F.; Lee, I. R.; Yeh, Y. C., Determination of gold ions in human urine using genetically engineered microorganisms on a paper device. ACS sensors. 2018, 3 (4), 744-748.
    30.Kylilis, N.; Riangrungroj, P.; Lai, H. E.; Salema, V.; Fernández, L. A. n.; Stan, G. B. V.; Freemont, P. S.; Polizzi, K. M., Whole-Cell Biosensor with Tunable Limit of Detection Enables Low-Cost Agglutination Assays for Medical Diagnostic Applications. ACS sensors. 2019, 4 (2), 370-378.
    31.Guo, K. H.; Lu, K. H.; Yeh, Y. C., Cell-Based Biosensor with Dual Signal Outputs for Simultaneous Quantification of Phenylacetic Acid and Phenylethylamine. ACS synthetic biology. 2018, 7 (12), 2790-2795.
    32.McFarland, D. C., Preparation of pure cell cultures by cloning. Methods in cell science. 2000, 22 (1), 63-66.
    33.Green, M. R.; Sambrook, J., Molecular cloning. A Laboratory Manual 4th. 2012.
    34.De Robertis, E. M., Spemann's organizer and self-regulation in amphibian embryos. Nature reviews Molecular cell biology. 2006, 7 (4), 296.
    35.Lassen, J.; Gjerris, M.; Sandøe, P., After Dolly—Ethical limits to the use of biotechnology on farm animals. Theriogenology. 2006, 65 (5), 992-1004.
    36.Jackson, D. A.; Symons, R. H.; Berg, P., Biochemical method for inserting new genetic information into DNA of Simian Virus 40: circular SV40 DNA molecules containing lambda phage genes and the galactose operon of Escherichia coli. Proceedings of the National Academy of Sciences. 1972, 69 (10), 2904-2909.
    37.Meyer, A.; Panke, S., Genomics in metabolic engineering and biocatalytic applications of the pollutant degradation machinery. Microbial Biodegradation: Genomics and Molecular Biology. 2008.
    38.Nataro, J. P.; Kaper, J. B., Diarrheagenic escherichia coli. Clinical microbiology reviews. 1998, 11 (1), 142-201.
    39.Dietzman, D. E.; Fischer, G. W.; Schoenknecht, F. D., Neonatal Escherichia coli septicemia—bacterial counts in blood. The Journal of pediatrics. 1974, 85 (1), 128-130.
    40.Levine, M. M., Escherichia coli that cause diarrhea: enterotoxigenic, enteropathogenic, enteroinvasive, enterohemorrhagic, and enteroadherent. The University of Chicago Press. 1987.
    41.Goeddel, D. V.; Kleid, D. G.; Bolivar, F.; Heyneker, H. L.; Yansura, D. G.; Crea, R.; Hirose, T.; Kraszewski, A.; Itakura, K.; Riggs, A. D., Expression in Escherichia coli of chemically synthesized genes for human insulin. Proceedings of the National Academy of Sciences. 1979, 76 (1), 106-110.
    42.Tabor, S.; Richardson, C. C., A bacteriophage T7 RNA polymerase/promoter system for controlled exclusive expression of specific genes. Proceedings of the National Academy of Sciences. 1985, 82 (4), 1074-1078.
    43.Casadaban, M. J., Transposition and fusion of the lac genes to selected promoters in Escherichia coli using bacteriophage lambda and Mu. Journal of molecular biology. 1976, 104 (3), 541-555.
    44.Menart, V.; Jevševar, S.; Vilar, M.; Trobiš, A.; Pavko, A., Constitutive versus thermoinducible expression of heterologous proteins in Escherichia coli based on strong PR, PL promoters from phage lambda. Biotechnology and bioengineering. 2003, 83 (2), 181-190.
    45.Tucker, D. L.; Tucker, N.; Conway, T., Gene expression profiling of the pH response in Escherichia coli. Journal of Bacteriology. 2002, 184 (23), 6551-6558.
    46.Sinensky, M., Temperature control of phospholipid biosynthesis in Escherichia coli. Journal of bacteriology. 1971, 106 (2), 449-455.
    47.El-Mansi, E.; Holms, W. H., Control of carbon flux to acetate excretion during growth of Escherichia coli in batch and continuous cultures. Microbiology. 1989, 135 (11), 2875-2883.
    48.Pei, Y.; Asif-Malik, A.; Canales, J. J., Trace amines and the trace amine-associated receptor 1: pharmacology, neurochemistry, and clinical implications. Frontiers in neuroscience. 2016, 10, 148.
    49.Burchett, S. A.; Hicks, T. P., The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain. Progress in neurobiology. 2006, 79 (5-6), 223-246.
    50.Berry, M. D., The potential of trace amines and their receptors for treating neurological and psychiatric diseases. Reviews on recent clinical trials. 2007, 2 (1), 3-19.
    51.Nakamura, M.; Ishii, A.; Nakahara, D., Characterization of β-phenylethylamine-induced monoamine release in rat nucleus accumbens: a microdialysis study. European journal of pharmacology. 1998, 349 (2-3), 163-169.
    52.Irsfeld, M.; Spadafore, M.; Prüß, B. M., β-phenylethylamine, a small molecule with a large impact. Webmedcentral. 2013, 4 (9).
    53.Potkin, S. G.; Karoum, F.; Chuang, L. W.; Cannon Spoor, H.; Phillips, I.; Wyatt, R. J., Phenylethylamine in paranoid chronic schizophrenia. Science. 1979, 206 (4417), 470-471.
    54.Bruinsma, K.; Taren, D. L., Chocolate: food or drug? Journal of the American Dietetic Association. 1999, 99 (10), 1249-1256.
    55.Vorce, S. P.; Sklerov, J. H., A general screening and confirmation approach to the analysis of designer tryptamines and phenethylamines in blood and urine using GC-EI-MS and HPLC-electrospray-MS. Journal of analytical toxicology. 2004, 28 (6), 407-410.
    56.Corse, J. W.; Jones, R. G.; Soper, Q. F.; Whitehead, C. W.; Behrens, O. K., Biosynthesis of Penicillins. V. 1 Substituted Phenylacetic Acid Derivatives as Penicillin Precursors. Journal of the American Chemical Society. 1948, 70 (9), 2837-2843.
    57.Adams, R.; Thal, A. F., Benzyl cyanide. Organic Syntheses. 1922, 9-9.
    58.Janssen, P. A.; Leysen, J. E.; Megens, A. A.; Awouters, F. H., Does phenylethylamine act as an endogenous amphetamine in some patients? International Journal of Neuropsychopharmacology. 1999, 2 (3), 229-240.
    59.Diamond, A.; Prevor, M. B.; Callender, G.; Druin, D. P., Prefrontal cortex cognitive deficits in children treated early and continuously for PKU. Monographs of the society for research in child development. 1997, i-206.
    60.Dierckx, S.; Van Puyvelde, S.; Venken, L.; Eberle, W.; Vanderleyden, J., Design and construction of a whole cell bacterial 4-hydroxyphenylacetic acid and 2-phenylacetic acid bioassay. Frontiers in bioengineering and biotechnology. 2015, 3, 88.
    61.Weng, J. R.; Tsai, C. H.; Kulp, S. K.; Chen, C. S., Indole-3-carbinol as a chemopreventive and anti-cancer agent. Cancer letters. 2008, 262 (2), 153-163.
    62.TANAKA, T., Cancer chemoprevention by natural-products. Oncology reports. 1994, 1 (6), 1139-1155.
    63.Murray, R. D. H.; Méndez, J.; Brown, S. A., The natural coumarins. 1982.
    64.Lacy, A.; O'kennedy, R., Studies on coumarins and coumarin-related compounds to determine their therapeutic role in the treatment of cancer. Current pharmaceutical design. 2004, 10 (30), 3797-3811.
    65.Dı́az, E.; Ferrández, A.; Prieto, M. a. A.; Garcı́a, J. L., Biodegradation of aromatic compounds byEscherichia coli. Microbiol. Mol. Biol. Rev. 2001, 65 (4), 523-569.
    66.Yamashita, M.; Azakami, H.; Yokoro, N.; Roh, J.-H.; Suzuki, H.; Kumagai, H.; Murooka, Y., maoB, a gene that encodes a positive regulator of the monoamine oxidase gene (maoA) in Escherichia coli. Journal of bacteriology. 1996, 178 (10), 2941-2947.
    67.Zeng, J.; Spiro, S., Finely tuned regulation of the aromatic amine degradation pathway in Escherichia coli. Journal of bacteriology. 2013, 195 (22), 5141-5150.
    68.Hanlon, S. P.; Hill, T. K.; Flavell, M. A.; Stringfellow, J. M.; Cooper, R. A., 2-Phenylethylamine catabolism by Escherichia coli K-12: gene organization and expression. Microbiology. 1997, 143 (2), 513-518.
    69.Steinebach, V.; Benen, J. A.; Bader, R.; Postma, P. W.; De Vries, S.; Duine, J. A., Cloning of the maoA gene that encodes aromatic amine oxidase of Escherichia coli W3350 and characterization of the overexpressed enzyme. European journal of biochemistry. 1996, 237 (3), 584-591.
    70.Ferrández, A.; Prieto, M. a. A.; Garcı́a, J. L.; Dı́az, E., Molecular characterization of PadA, a phenylacetaldehyde dehydrogenase from Escherichia coli. FEBS letters. 1997, 406 (1-2), 23-27.
    71.Parrott, S.; Jones, S.; Cooper, R. A., 2-Phenylethylamine catabolism by Escherichia coli K12. Microbiology. 1987, 133 (2), 347-351.
    72.Cooper, R.; Knowles, P.; Brown, D.; McGuirl, M.; Dooley, D.M., Evidence for copper and 3, 4, 6-trihydroxyphenylalanine quinone cofactors in an amine oxidase from the Gram-negative bacterium Escherichia coli K-12. Biochemical Journal. 1992, 288 (2), 337-340.
    73.Yang, H.; Wolff, E.; Kim, M.; Diep, A.; Miller, J. H., Identification of mutator genes and mutational pathways in Escherichia coli using a multicopy cloning approach. Molecular microbiology. 2004, 53 (1), 283-295.
    74.Kim, H. S.; Kang, T. S.; Hyun, J. S.; Kang, H. S., Regulation of penicillin G acylase gene expression in Escherichia coli by repressor PaaX and the cAMP-cAMP receptor protein complex. Journal of Biological Chemistry. 2004, 279 (32), 33253-33262.
    75.Ferrández, A.; Garcı́a, J. L.; Dı́az, E., Transcriptional Regulation of the Divergent paaCatabolic Operons for Phenylacetic Acid Degradation inEscherichia coli. Journal of Biological Chemistry. 2000, 275 (16), 12214-12222.
    76.Teufel, R.; Friedrich, T.; Fuchs, G., An oxygenase that forms and deoxygenates toxic epoxide. Nature. 2012, 483 (7389), 359.
    77.Ferrández, A.; Miñambres, B.; Garcı́a, B.; Olivera, E. a. R.; Luengo, J. M.; Garcı́a, J. L.; Dı́az, E., Catabolism of phenylacetic acid in Escherichia coli characterization of a new aerobic hybrid pathway. Journal of Biological Chemistry. 1998, 273 (40), 25974-25986.
    78.Al Hafid, N.; Christodoulou, J., Phenylketonuria: a review of current and future treatments. Translational pediatrics. 2015, 4 (4), 304.
    79.National Institutes of Health Consensus Development Panel, National institutes of health consensus development conference statement: phenylketonuria: screening and management. Pediatrics. 2001, 108 (4), 972-982.
    80.Grainger, D. C.; Busby, S. J., Global regulators of transcription in Escherichia coli: mechanisms of action and methods for study. Adv Appl Microbiol. 2008, 65, 93-113.
    81.Cooper, G. M.; Hausman, R. E.; Hausman, R. E., The cell: a molecular approach. ASM press Washington. DC, 2000; Vol. 10.
    82.Hanamura, A.; Aiba, H., A new aspect of transcriptional control of the Escherichia coli crp gene: positive autoregulation. Molecular microbiology. 1992, 6 (17), 2489-2497.
    83.Ramseier, T. M.; Saier Jr, M. H., cAMP-cAMP receptor protein complex: five binding sites in the control region of the Escherichia coli mannitol operon. Microbiology. 1995, 141 (8), 1901-1907.
    84.Hanamura, A.; Aiba, H., Molecular mechanism of negative autoregulation of Escherichia coli crp gene. Nucleic acids research. 1991, 19 (16), 4413-4419.
    85.Görke, B.; Stülke, J., Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Reviews Microbiology. 2008, 6 (8), 613.
    86.Salmon, K.; Hung, S. p.; Mekjian, K.; Baldi, P.; Hatfield, G. W.; Gunsalus, R. P., Global gene expression profiling in Escherichia coli K12 the effects of oxygen availability and FNR. Journal of Biological Chemistry. 2003, 278 (32), 29837-29855.
    87.Kang, Y.; Weber, K. D.; Qiu, Y.; Kiley, P. J.; Blattner, F. R., Genome-wide expression analysis indicates that FNR of Escherichia coli K-12 regulates a large number of genes of unknown function. Journal of Bacteriology. 2005, 187 (3), 1135-1160.
    88.Martin, D. B.; Vagelos, P. R., The mechanism of tricarboxylic acid cycle regulation of fatty acid synthesis. J Biol Chem. 1962, 237 (6), 1787-92.
    89.Stülke, J.; Hillen, W. J., Carbon catabolite repression in bacteria. Nature Reviews Microbiology. 1999, 2 (2), 195-201.
    90.Postma, P.; Lengeler, J. W., Phosphoenolpyruvate: carbohydrate phosphotransferase system of bacteria. Microbiological reviews. 1985, 49 (3), 232.
    91.Meadow, N. D.; Fox, D. K.; Roseman, S., The bacterial phosphoenol-pyruvate: glycose phosphotransferase system. Annual review of biochemistry. 1990, 59 (1), 497-542.
    92.Johnston, M.; Carlson, M., 5 regulation of carbon and phosphate utilization. Cold Spring Harbor Monograph Archive. 1992, 21, 193-281.
    93.Cameron, A. D.; Redfield, R. J., CRP binding and transcription activation at CRP-S sites. Journal of molecular biology. 2008, 383 (2), 313-323.
    94.Busby, S.; Ebright, R. H., Transcription activation by catabolite activator protein (CAP). Journal of molecular biology. 1999, 293 (2), 199-213.
    95.Lin, Y. K.; Yeh, Y. C., Dual-Signal Microbial Biosensor for the Detection of Dopamine without Inference from Other Catecholamine Neurotransmitters. Analytical chemistry. 2017, 89 (21), 11178-11182.
    96.Bren, A.; Park, J. O.; Towbin, B. D.; Dekel, E.; Rabinowitz, J. D.; Alon, U., Glucose becomes one of the worst carbon sources for E. coli on poor nitrogen sources due to suboptimal levels of cAMP. Scientific reports. 2016, 6, 24834.
    97.Mönch, E.; Kneer, J.; Jakobs, C.; Arnold, M.; Diehl, H.; Batzler, U., Examination of urine metabolites in the newborn period and during protein loading tests at 6 months of age—part 1. European journal of pediatrics. 1990, 149 (1), 17-24.
    98.Kusaga, A.; Yamashita, Y.; Koeda, T.; Hiratani, M.; Kaneko, M.; Yamada, S.; Matsuishi, T., Increased urine phenylethylamine after methylphenidate treatment in children with ADHD. Annals of neurology. 2002, 52 (3), 372-374.
    99.Bouatra, S.; Aziat, F.; Mandal, R.; Guo, A. C.; Wilson, M. R.; Knox, C.; Bjorndahl, T. C.; Krishnamurthy, R.; Saleem, F.; Liu, P., The human urine metabolome. PloS one. 2013, 8 (9), e73076.
    100.Gronwald, W.; Klein, M. S.; Zeltner, R.; Schulze, B. D.; Reinhold, S. W.; Deutschmann, M.; Immervoll, A. K.; Böger, C. A.; Banas, B.; Eckardt, K. U., Detection of autosomal dominant polycystic kidney disease by NMR spectroscopic fingerprinting of urine. Kidney international. 2011, 79 (11), 1244-1253.
    101.Cucchi, M. L.; Frattini, P.; Santagostino, G.; Preda, S.; Orecchia, G., Catecholamines increase in the urine of non‐segmental vitiligo especially during its active phase. Pigment cell research. 2003, 16 (2), 111-116.
    102.Nikolelis, D. P.; Drivelos, D. A.; Simantiraki, M. G.; Koinis, S., An optical spot test for the detection of dopamine in human urine using stabilized in air lipid films. Analytical chemistry. 2004, 76 (8), 2174-2180.

    下載圖示
    QR CODE