(3.236.214.19) 您好!臺灣時間:2021/05/10 08:03
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

: 
twitterline
研究生:蔡怡韋
研究生(外文):Yi-Wei Tsai
論文名稱:葡萄糖穩態控制醱酵對於基因重組E.coli細胞調控與ColicinE7Nuclease之生產研究
論文名稱(外文):The Study of Cellular Regulation and Colicin E7 Nuclease Production by Recombinant Escherichia coli in Glucose-stat Fed-batch Cultivation
指導教授:陳志成陳志成引用關係
指導教授(外文):C. Will Chen
學位類別:碩士
校院名稱:大同大學
系所名稱:生物工程學系(所)
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:183
中文關鍵詞:基因重組大腸桿菌葡萄糖穩態醱酵細胞調控去氧核醣核酸水解酶
外文關鍵詞:Recombinant E. coliGlucose-stat Fed-batchCellular RegulationDNase
相關次數:
  • 被引用被引用:2
  • 點閱點閱:274
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:20
  • 收藏至我的研究室書目清單書目收藏:0
由於肺部疾病的濃痰含有大量的deoxyribonucleic acid (DNA),而deoxyribonuclease (DNase) 可以水解大分子的DNA而形成小片段的分子便於人體排泄,進而明顯改善肺部疾病之併發症,所以DNase具有很大的的市場價值。本研究利用glucose-stat醱酵方法,於碳氮源1:0,1:1或2:1 (Glucose/Yeast extract, w/w) 饋料條件下控制培養基中葡萄糖濃度於0.1,1.0與5.0 g/L,而培養Escherichia coli DH5α生產含有核酸水解酶 (nuclease domain) 與免疫蛋白 (immunity protein, Im7) 之coliciny Im7 complex,並探討菌體細胞內調控性分子與colicin E7 nuclease表現量之關係。由於核酸水解酶為細胞毒素,所以當isopropyl-β-D-thiogalactopyranoside (IPTG) 進行誘導表現時,必須藉由coliciny Im7 complex的生成以降低細胞毒素的毒性。當培養基中葡萄糖維持於偏高 (5 g/L) 的培養條件下,於生長時期與誘導期間細胞內調控性分子Guanosine 3’,5’-bispyrophosphate (ppGpp) 濃度保持1.3μmol/g cell以上或生長時期Adenosine 3’,5’-monophosphate (cAMP) 維持於0.7μmol/g cell以下,且添加誘導劑IPTG後,細胞內adenylate/ guanylate energy charge (A/G EC) 變動幅度較大,因而造成細胞乾重濃度與colicin E7 nuclease活性表現量偏低 (分別為8.6 g/L與50680 U/L)。反之,當葡萄糖濃度維持於較低 (0.1 g/L) 的培養條件下,細胞內ppGpp濃度可維持於1.0μmol/g cell以下與cAMP維持於0.7μmol/g cell以上,且細胞內A/G energy charge變動幅度也較小,因此細胞乾重濃度與colicin E7 nuclease活性表現量也相對提升,分別可達13.8 g/L與331900 U/L。而進一步發現,於低葡萄糖濃度 (0.1 g/L) 且醱酵培養液中持續添加酵母萃取物時,有助於減緩細胞內ppGpp生成且縮小A/G energy chargy之變動幅度,而獲得最佳的colicin E7 nuclease之活性表現,可達到622300 U/L。本研究發現影響細胞生長與蛋白質產量之關鍵因素主要依靠細胞內調控性分子 (如:ppGpp與cAMP) 的協調與energy charge之穩定性,因此如能即時監控細胞內調控訊息,將有助於掌控細胞生長、代謝穩定度與基因重組蛋白質產量之提升。
Phlegm in serious lung disease contained much deoxyribonucleic acid (DNA), but deoxyribonuclease (DNase) could hydrolyze DNA to fragments for better body secretion to reduce complication. Therefore, DNase has commercial potential in medical market. In this study, we use glucose-stat strategy to control the glucose concentration of fermentation broth at 5, 1 and 0.1 g/L, along with feeding stream of different ratio of Glucose/Yeast extract (w/w) at 1/0, 1/1 or 2/1 to product coliciny Im7 complex. The coliciny Im7 complex consists of a nuclease domain and its immunity protein (Im7) from a recombinant Escherichia coli DH5α. We also study the relation between intracellular alarmones, e.g. ppGpp (guanosine 3’,5’-bispyrophosphate) or cAMP (adenosine 3’,5’-monophosphate), nucleotide triphosphate (NTP), energy charge and coliciny Im7 production. Since the nuclease activity is cytotoxic, the cell biomass may be degraded after isopropyl-β-D-thiogalactopyranoside (IPTG) induction for gene expression. Therefore, it is beneficial to reduce the cytotoxicity of nuclease domain by forming coliciny Im7 complex. We found that higher glucose concentration (at 5 g/L) resulted in higher intracellular ppGpp (above 1.3μmol/g cell) during growth and induction phase and also lower cAMP (below 0.7μmol/g cell) during growth phase, in addition, an unstable adenylate/ guanylate energy charge (A/G EC) after IPTG induction. Therefore, in such situation resulted in a lower cell concentration and volumetric nuclease activity of coliciny Im7 complex at 8.6 g/L and 50680 U/L, respectively. On the contrary, lower glucose concentration (0.1 g/L) resulted in lower intracellular ppGpp (below 1.0μmol/g cell), higher cAMP (above 0.7μmol/g cell), and more stable A/G energy charge. Therefore, in such situation, the cell concentration and volumetric nuclease activity of coliciny Im7 complex were increased to be 18.6 g/L and 331900 U/L, respectively. Besides, by feeding yeast extract during post-induction stage at low glucose level (0.1 g/L) resulted in reducing intracellular ppGpp concentration and also a much stable A/G energy charge that produced a much higher volumetric nuclease activity of coliciny Im7 complex (622300 U/L). In this study we conclude that the key factors that affect the cell growth and recombinant protein production shall be the proper range of intracellular alarmones, e.g. ppGpp or cAMP and also the stability of energy charge. The detection of such intracellular information is critical for a better control of cell growth and protein production from a recombinant E. coli.
摘要.i
英文摘要iii
目錄v
圖目錄ix
表目錄xii
壹、 序論1
1.1 前言1
1.2 研究動機2
貳、 文獻探討4
2.1 利用基因轉殖Escherichia coli生產重組蛋白質4
2.1.1 蛋白質藥物市場分析4
2.1.2 高密度醱酵培養基因轉殖Escherichia coli. 11
2.2 醱酵過程之細胞內調控訊號與其應用13
2.2.1 Metabolic load sensor13
2.2.2 NXP Pools之研究14
2.2.3 Adenosine 3’,5’-monophosphate (cAMP) 之研究20
2.2.3.1 cAMP細胞內調控 (Global regulatory) 20
2.2.3.2 cAMP之生成與分解25
2.2.4 Guaosine 3’, 5’-bispyrophosphate (ppGpp) 之研究29
2.2.4.1 ppGpp細胞內調控 (Global regulatory) 29
2.2.4.2 ppGpp之生成與分解33
2.3 大腸桿菌素之介紹36
2.3.1 大腸桿菌素的分類36
2.3.2 大腸桿菌素殺菌機制36
2.3.3 大腸桿菌素相關基因37
2.3.4 DNase功用38
參、 材料與方法40
3.1 實驗儀器40
3.2 實驗材料41
3.2.1 菌種來源41
3.2.2 藥品41
3.3 菌種保存與培養方法42
3.3.1 菌種保存42
3.3.2 菌種活化與種菌培養43
3.3.3 醱酵培養44
3.3.3.1 醱酵槽配置44
3.3.3.2 接菌培養45
3.3.3.3 電腦監控系統46
3.3.3.4 Glucose-stat批次饋料醱酵46
3.4 樣本分析方法49
3.4.1 菌體濃度與細胞乾重之定量49
3.4.2 菌體生長之參數分析49
3.4.3 高壓液相層析儀分析50
3.4.3.1 醱酵菌液內醣類與有機酸含量之測定50
3.4.3.2 菌體內ppGpp、cAMP、ATP、GTP濃度之測定51
3.4.4 氨氮含量之測定法51
3.4.5 TKN之含量測定法52
3.4.6 蛋白質之濃度測定54
3.5 大腸桿菌素與帶有His tag之免疫蛋白質複體的純化54
3.5.1 Colicin E7 nuclease之純化54
3.5.2 Colicin E7 nuclease之活性測試56
3.5.2.1 DNA濃度測定之標準曲線作法56
3.5.2.2 Colicin E7 nuclease活性測定57
肆、 結果與討論58
4.1 利用Glucose-stat醱酵培養基因轉殖Escherichia coli生產Colicin E7 Nuclease58
4.1.1 控制培養基中葡萄糖於不同濃度下培養基因轉殖Escherichia coli58
4.1.2 於饋料模式下添加不同比例之酵母萃取物培養基因轉殖Escherichia coli67
4.2 醱酵過程中監控細胞能量與細胞調控訊號之變化74
4.2.1 利用High Performance Liquid Chromatography (HPLC) 分析細胞內NXP濃度變化74
4.2.2 控制培養基中不同葡萄糖濃度培養E. coli,並探討細胞內NXP濃度之變化76
4.2.2.1 細胞內NXP Pools變化.76
4.2.2.2 細胞內能荷 (Energy charge) 變化86
4.2.2.1 細胞內Adenylate Energy charge (AEC) 之變化86
4.2.2.2 細胞內Guanylate Energy charge (GEC)之變化89
4.2.3 控制不同葡萄糖濃度之醱酵條件探討基因重組E. coli細胞內訊號生成與調控92
伍、 結論107
陸、 未來研究方向之建議 110
柒、 參考文獻111
捌、 附錄130
財團法人生物技術開發中心,2003,生物技術產業年鑑2003,全華科技。
吳文騰,2003,生物產業技術概論,國立清華大學出版社。
廖辰中,2000,大腸桿菌素E7毒性功能區運送機制的研究。碩士論文,陽明大學生物化學所。
雷博欽,2006,以限制葡萄糖濃度饋料醱酵培養重組大腸桿菌生產Colincin E7 Nuclease之研究。博士論文,大同大學生物工程所。
Åkesson, M., E. N. Karlsson, P. Hagander, J. P. Axelsson, and A. Tocaj. 1999. On-line detection of acetate formation in Escherichia coli cultures using dissolved oxygen responses to feed transients. Biotechnol. Bioeng. 64: 590-598.
Åkesson, M., P. Hagander, and J. P. Axelsson. 2001. Avoiding acetate accumulation Escherichia coli in cultures using feedback control of glucose feeding. Biotechnol. Bioeng. 73: 223-230.
Andersson, L., S. Yang, P. Neubauer, and S.-O. Enfors. 1996. Impact of plasmid presence and induction on cellular responses in fed batch cultures of Escherichia coli. J. Biotechnol. 46: 255-263.
Balloy, V., J.-M. Sallenave, B. Crestani, M. Dehoux, and M. Chignard. 2003. Neutrophil DNA Contributes to the antielastase barrier during acute lung inflammation. Am. J. Respir. Cell Mol. Biol. 28: 746-753.
Barrette, W. C., JR. D. M. Hannum, W. D. Wheeler, and J. K. Hurst. 1988. Viability and metabolic capability are maintained by Escherichia coli, Pseudomonas aeruginosa, and Streptococcus lactis at very low adenylate energy charge. J. Bacteriol. 170: 3655-3659.
Bentley, W. E., N. Mirjalili, D. C. Andersen, R. H. Davis, and D. S. Kompala. 1990. Plasmid encoded protein: the principal factor in the “metabolic burden” associated with recombinant bacteria. Biotechnol. Bioeng. 35: 668-661.
Bettenbrock, K., T. Sauter, K. Jahreis. A. Kremling, J. W. Lengeler, and E.-R. Gilles. 2007. Correlation between growth rates, EIIGlc phosphorylation and intracellular cyclic AMP levels in Escherichia coli K-12. J. Bacteriol. 189: 6891-6900.
Boogaard, R., J. C. De Jongste, and P. J. MerKus. 2007. Pharmacotherapy of impaired mucociliary clearance in non-CF pediatric lung disease. A review of the literature. Pediatr. Pulmonol. 42: 989-1001.
Botsford, J. L., and J. G. Harman. 1992. Cyclic AMP in prokaryotes. Microbiol. Rev. 56: 100-122.
Braeken, K., M. Moris, R. Daniels, J. Vanderleyden, and J. Michiels. 2006. New horizons for (p)ppGpp in bacterial and plant physiology. Trends Microbiol. 14: 45-54.
Brown, L., D. Gentry, T. Elliott, and M. Cashel. 2002. DksA affects ppGpp induction of RopS at a translational level. J. Bacteriol. 184: 4455-4465.
Busby, S., and R. H. Ebright. 1999. Transcription Activation by Catabolite Activator Protein (CAP). J. Mol. Biol. 293: 199-213.
Buckstein, M. H., J. He, and H. Rubin. 2008. Characterization of nucleotide pools as a function of physiological state in Escherichia coli. J. Biotechnol. 190: 718-726.
Cashel, M., D. R. Gentry, V. J. Hernandez, and I. D. Spenser. 1996. The stringent response. 1458-1496. In F. C. Neidhardt (ed.), Escherichia coli and Salmonella: cellular and moleculare biology, 2nd ed., vol. 1. ASM Press, Washington, D. C.
Chapman, S. G., L. Fall, and D. E. Atkinson. 1971. Adenylate energy charge in Escherichia coli during growth and starvation. J. Bacteriol. 108: 1072-1086.
Chatterji, D., and A. K. Ojha. 2001. Revisiting the stringent response, ppGpp and starvation signal. Curr. Opin. Microbiol. 4: 160-165.
Chen, C. W., B. C. Lei, K. W. Yeh, and K. J. Duan. 2003. Recombinant sweet potata sporamin production via glucose/pH control in fed-batch culture of Saccharomyces cerevisiae. Process Biochem. 38: 1223-1229.
Choi, D. B., and E. Y. Park. 2006. Enhanced production of mouse α-amylase by feeding combined nitrogen and carbon sources in fed-batch culture of recombinant Pichia pastoris. Process Biochem. 41: 390-397.
Cserjan-Puschmann, M., W. Kramer, E. Duerrschmid, G. Striedner, and K. Bayer. 1999. Metabolic approaches for the optimization of recombionant fermentation processes. Appl. Microbiol. Biotechnol. 53: 43-50.
Curless, C., J. Pope, and L. Tsai. 1990. Effect of preinduction specific growth rate on recombinant alpha consensus interferon synthesis in Escherichia coli. Biotechnol. Prog. 6: 149-152.
Dedhia, N., R. Richins, A. Mesina, and W. Chen. 1997. Improvement in recombinant protein production in ppGpp-deficient Escherichia coli. Biotechnol. Bioeng. 53: 379-386.
Dennis, P. P., M. Ehrenberg, and H. Bremer. 2004. Control of rRNA synthesis in Escherichia coli: a systems biology approach. Microbiol. Mol. Biol. Rev. 68: 639-668.
Deutscher, J., C. Francke, and P. W. Postma. 2006. How phosphotransferase system-related protein phosphorylation regulates carbohydrate metabolism in bacteria. Microbiol. Mol. Biol. Rev. 70: 939-1031.
DiRusso, C. C., and T. Nystrom. 1998. The fats of Escherichia coli during infancy and old age: regulation by global regulators, alarmones and lipid intermediates. Mol. Microbiol. 27: 1-8.
Dodge, T. C., and J. M. Gerstner. 2002. Optimization of the glucose feed rate profile for the production of tryptophan from recombinant E. coli. J. Chem. Technol. Biotechnol. 77: 1238-1245.
Dong, X.-Y., M.-L. Fu, and Y. Sun. 2008. Refolding of recombinant homodimeric malate dehydrogenase expressed in Escherichia coli as inclusion bodies. Biochem. Eng. J. 38: 341-348.
Donovan, R. S., C. W. Robinson, and B. R. Glick. 1996. Review: Optimizing inducer and culture conditions for expression of foreign proteins under the control of the lac promoter. J. Ind. Microbiol. 16: 145-154.
Ford, S. R., M. S. Hall, V. R. Vaden, J. J. Webster, F. R. Leach, J. J. Webster, and F. R. Leach. 1994. Adenylate and guanlyate energy charges in subsurface Pseudomonas sp. Proceedings of the Oklahoma Academy of Science. 74: 31-36.
Fuchs, C., D. Koster, S. Wiebusch, K. Mahr, G. Eisbrenner, and H. Markl. 2002. Scale-up of dialysis fermentation for high cell density cultivation of Escherichia coli. J. Biotechnol. 93: 243–251.
Gaal, T., M. S. Bartlett, W. Ross, C. L. Turnbough Jr., and R. L. Gourse. 1997. Transcription regulation by initiating NTP concentration: rRNA synthesis in bacteria. Science. 278: 2092-2097.
Gebelein, M, G. Merdes, and MR. Berger. 1992. Nucleotide preparation from cells and determination of nucleotides by ion-pair high-performance liquid chromatography. J. Chromatogr. 557: 146-150.
Gentry, D. R., V. J. Hernandez, L. H. Nguyen, D. B. Jensen, and M. Cashel. 1993. Synthesis of the stationary-phase factor σS is positively regulated by ppGpp. J. Bacteriol. 175: 7982-7989.
Gentry, D. R., and M. Cashel. 1995. Cellular localization of the Escherichia coli SpoT protein. J. Bacteriol. 177: 3890-3893.
Glick, B. R. 1995. Metabolic load and heterologous gene expression. Biotechnol. Adv. 13: 247-261.
Gourse, R. L., T. Gaal, M. S. Bartlett, J. A. Appleman, and W. Ross. 1996. rRNA transcription and growth rate-dependent regulation of ribosome synthesis in Escherichia coli. Annu. Rev. Microbiol. 50: 645-677.
Gupta, R., P. Sharma, and V. V. Vyas. 1995. Effect of growth environment on the stability of a recombinant shuttle plasmid, Pcpps-31, in Escherichia coli. J. Biotechnol. 41: 29-37.
Han, K., H. C. Lim, and J. Hong. 1992. Acetic acid formation in Escherichia coli fermentation. Biotechnol. Bioeng. 39: 663-671.
Hara, A., and J. Sy. 1983. Guanosine 5’-triphosphate, 3’-diphosphate 5’-phospho hydrolase. Purification and substrate specificity. J. Biol. Chem. 258: 1678–1683.
Harcum, S. W., D. M. Ramirez, and W. E. Bentley. 1992. Optimal nutrient feed policies for heterologous protein production. Appl. Biochem. Biotechnol. 34/35: 161-73.
Heath, R. J., S. Jackowski, and C. O. Rock. 1994. Guanosine tetraphosphate inhibition of fatty acid and phospholipid synthesis in Escherichia coli is relieved by overexpression of glycerol-3-phosphate acyltransferase (plsB). J. Biol. Chem. 269: 26584-26590.
Helinski, D. R., A. E. Toukdarian, and R. P. Novick. 1996. Replication control and other stable maintenance mechanisms of plasmid. 2295-2324. In F. C. Neidhardt (ed.), Escherichia coli and Salmonella: cellular and moleculare biology, 2nd ed., vol. 1. ASM Press, Washington, D. C.
Hellmuth, K., D. J. Korz, E. A. Sanders, and W. D. Deckwer. 1994. Effect of growth rate on stability and gene expression of recombinant plasmids during continuous and high cell density cultivation of Escherichia coli TG1. J. Biotechnol. 32: 289-298.
Hengge-Aronis, R. 2002. Signal transduction and regulatory mechanisms involved in control of the σS (RpoS) subunit of RNA polymerase. Microbiol. Mol. Biol. Rev. 66:373-395.
Herman, A., and G. Wegrzyn. 1995. Effect of increased ppGpp concentration on DNA replication of different replicons in Escherichia coli. J. Basic Microbiol. 35: 33-39.
Hewitt, C. J., and G. Nebe-Von-Caron. 2001. An industrial application of multi-parameter flow cytometry: assessment of cell physiological state and its application to the study of microbial fermentations. Cytometry. 44: 179-187.
Hockney, R. C. 1994. Recent developments in heterologous protein production in Escherichia coli. Trends Biotechnol. 12: 456-463.
Hoffmann, F., J. Weber, and U. Rinas. 2002. Metabolic adaptation of Escherichia coli during temperature-induced recombinant protein production: 1. readjustment of metabolic enzyme synthesis. Biotechnol. Bioeng. 80: 313-319.
Horn, U., W. Strittmatter, A. Krebber, U. Knupfer, M. Kujau, R. Wenderoth, K. Muller, S. Matzku, A. Pliuckthum, and D. Riesenberg. 1996. High volumetric yields of functional dimeric miniantibodies in Escherichia coli, using an optimized expression vector and high-cell-density fermentation under non-limited growth conditions. Appl. Microbiol. Biotechnol. 46: 524-532.
Imaizumi, A., H. Kojima, and K. Matsui. 2006. The effect of intracellular ppGpp levels on glutamate and lysine overproduction in Escherichia coli. J. Biotechnol. 125: 328-337.
Ishihama, A. 1999. Modulation of the nucleoid, the transcription apparatus, and the translation machinery in bacteria for stationary phase survival. Gene. Cell. 4: 135-143.
James, R., C. Kleanthous, and G. R. Moore. 1996. The biology of E colicines: paradigms and paradoxes. Microbiology. 142: 1569-1580.
Jung, G., P. Denefle, J. Becquart, and J. F. Mayaux. 1988. High-cell density fermentation studies of recombinant Escherichia coli strains expression expression human interleukin-lb. Ann. Inst. Pasteur Microbiol. 139: 129-146.
Kahru, A., and R. Vilu. 1983. On characterization of the growth of Escherichia coli in batch culture. Arch Microbiol. 135: 12-15.
Karl, D. M., and O. Holm-Hansen. 1978. Methodology and measurement of adenylate energy charge ratios in environmental samples. Mar. Biol. 48: 185-197.
Karl, D. M. 1980. Cellular nucleotide measurements and applications in microbial ecology. Microbiol. Rev. 44: 739-796.
Kleman, G. L., and W. R. Strohl. 1994. Developments in high cell density and high productivity microbial fermentation. Curr. Opin. Biotechnol. 5: 180-186.
Koh, B. T., U. Nakashimada, M. Pfeiffer, and M. G. S. Yap. 1992. Comparison of acetate inhibition on growth host and recombinant E. coli K12 strains. Biotechnol. Lett. 14: 1115-1118.
Kosinski, M. J., U. Rinas, and J. E. Bailey. 1992. Isopropyl-β-D- thiogalactopyranos ide influences the metabolism of Escherichia coli. Appl. Microbiol. Biotechnol. 36: 782-784.
Kurland, C. G., and H. Dong. 1996. Bacterial growth inhibition by overproduction of protein. Mol. Microbiol. 21: 1-4.
Lapin, A., J. Schmid, and M. Reuss. 2006. Modeling the dynamics of E. coli populations in the three-dimensional turbulent field of a stirred-tank bioreactor-a structured –segregated approach. Chem. Eng. Sci. 61: 4783-4797.
Lasko, D. R., D. I. C. Wang. 1996. On-line monitoring of intracellular ATP concentration in Escherichia coli fermentations. Biotechnol. Bioeng. 52: 364-372.
Lazdunski, C. J., E. Bouveret, A. Rigal, L. Journet, R. Lloubes, and H. Benedetti. 1998. Colicin import into Escherichia coli cells. J. Bacteriol. 180: 4993-5002.
Lee, S. Y. 1996. High cell-density culture Escherichia coli. Trends Biotechnol. 14: 98-105.
Lee, Y. L., and H. N. Chang. 1990. High cell density culture of a recombinant Escherichia coli producing penicillin acylase in a membrane cell recycle fermentor. Biotechnol. Bioeng. 26: 330–337.
Li, Y., J. Chen, Y. Y. Mao, S. Y. Lun, and Y. M. Koo. 1998. Effect of additives and fed-batch culture strategies on the production of glutathione by recombinant Escherichia coli. Process Biochem. 33: 709-714.
Lin, H. Y., and P. Neubauer. 2000. Influence of controlled glucose oscillation on a fed-batch process of recombinant Escherichia coli. J. Biotechnol. 79: 27-37.
Lin, H. Y., B. Mathiszik, B. Xu, S.-O. Enfors, and P. Neubauer. 2001. Determination of the maximum specific uptake capacities for glucose and oxygen in glucose-limited fed-batch cultivations of the Escherichia coli. Biotechnol. Bioeng. 73: 347-357.
Lin, H., F. Hoffmann, A. Rozkov, S.-O. Enfors, U. Rinas, and P. Neubauer. 2004. Chang of extracellular cAMP concentration is a sensitive reporter for bacterial fitness in high-cell-density cultures of Escherichia coli. Biotechnol. Bioeng. 87: 602-613.
Lowry, O. H., J. Carter, J. B. Ward, and L. Glaser. 1971. The effect of carbon and nitrogen sources on the level of metabolic intermediates in Escherichia coli. J. Biol. Chem. 246: 6511-6521.
Luli, G. W., and W. R. Strohl. 1990. Comparison of growth, acetate production, and acetate inhibition of Escherichia coli strains in batch and fed-batch fermentations. Appl. Environ. Microbiol. 56: 1004-1011.
Magnusson, L. U., T. Nystrom, and A. Farewell. 2003. Underproduction of σ70 mimics a stringent response: a proteome approach. J. Biol. Chem. 278: 968-973.
Magnusson, L. U., A. Farewell, and T. Nystrom. 2005. ppGpp: a global regulator in Escherichia coli. 13:236-242.
Maheswaran, M., and K. Forchhammer. 2003. Carbon-source-dependent nitrogen regulation in Escherichia coli is mediated through glutamine-dependent GlnB signalling. Microbiology 149:2163–2172.
Makman, R. S., and E. W. Sutherland. 1965. Adenosine 3’,5’-phosphate in Escherichia coli. J. Bio. Chem. 240: 1309-1314.
Mao, X. J., Y. X. Huo, M. Buck, A. Kolb, and Y. P. Wang. 2007. Interplay between CRP-cAMP and PII-Ntr systems forms novel regulatory network between carbon metabolism and nitrogen assimilation in Escherichia coli. Nucleic Acids Res. 35: 1432 – 1440.
Matin, A., and M. K. Matin. 1982. Cellular levels, excretion, and synthesis rates of cyclic AMP in Escherichia coli grown in continuous culture. J. Bacteriol. 149: 801-807. Mukhopadhyay, J., R. Sur, and P. Parrack. 1999. Functional roles of the two cyclic AMP receptor protein from Escherichia coli. FEBS Lett. 453: 215-218.
Meyer, S., N. Noisommit-Rizzi, M. Reuss, and P. Neubauer. 1999. Optimized analysis of intracellular adenosine and guanosine phosphates in Escherichia coli. Anal. Biochem. 271: 43-52.
Murray, K. D., and H. Bremer. 1996. Control of SpoT-dependent ppGpp Synthesis and degradation in Escherichia coli. J. Mol. Biol. 259: 41-57.
Murrary, H. D., D. A. Schneider, and R. L. Gourse. 2003. Control of rRNA expression by small molecules is dynamic and nonredundant. Mol. Cell. 12: 125-134.
Mukhopadhyay, J., R. Sur, and P. Parrack. 1999. Functional roles of the two cyclic AMP-dependent forms of cyclic AMP receptor protein from Escherichia coli. FEBS Lett. 453: 215-218.
Nancib, N., C. Branlant, and J. Boudrant. 1991. Metabolic roles of peptone and yeast extract for the culture of a recombinant strain of Escherichia coli. J. Ind. Microbiol. 8: 165-170.
Neubauer, P., M. Ahman, M. Tornkvist, G. Larsson, and S.-O. Enfors. 1995. Response of guanosine tetraphosphate to glucose fluctuations in fed-batch cultivations of Escherichia coli. J. Biotechnol. 43: 195-204.
Neidhardt, F. C., and M. A. Savageau. 1996. Regulation beyond the operon. 1310-1324. In F. C. Neidhardt (ed.), Escherichia coli and Salmonella: cellular and molecular biology, 2nd ed., vol. 1. ASM Press, Washington, D. C.
Nelson, D. L., and M. M. Cox. 2005. Lehninger: Principles of biochemistry. 4nd ed. W. H. Freeman and Company. New York.
Notley, L., and T. Ferenci. 1996. Induction of RopS-dependent functions in glucose-limited continuous culture: what level of nutrient limitation induces the stationary phase of Escherichia coli. J. Bacteriol. 178: 1465-1468.
Notley-McRobb L., A. Death, and T. Ferenci. 1997. The relationship between external glucose concentration and cAMP levels inside Escherichia coli: implications for models of phosphotransferase-mediated regulation of adenylate cyclase. Microbiology. 143: 1909-1918.
O’Berine, D., and G. Hamer. 2000. The utilization of glucose/acetate mixtures by Escherichia coli W3110 under aerobic growth conditions. Bioprocess Eng. 23: 375-380.
Pack, P., M. Kujau, V. Schroeckh, U. Knupfer, R. Wenderoth, D. Reisenberg, and A. Pluckthun. 1993. Improved bivalent miniantibodies, with identical avidity as whole antibodies, produced by high cell density fermentation of Escherichia coli. Bio/Technology. 11: 1271-1277.
Panda, A. K., R. H. Khan, S. Mishra, K. B. C. Appa Rao, and S. M. Totey. 2000. Influences of yeast extract on specific cellular yield of ovine growth hormone during fed-batch fermentation of E. coli. Bioprocess eng. 22: 379-383.
Patten, C. L., M. G. Kirchhof, M. R. Schertzberg, R. A. Morton, and H. E. Schellhorn. 2004. Microarray analysis of RpoS-mediated gene expression in Escherichia coli K-12. Mol. Genet. Genom. 272, 580–591.
Paul, B. J., W. Ross, T. Gaal, and R. L. Gourse. 2004. rRNA transcription in Escherichia coli .Annu. Rev. Genet. 38: 749-770.
Pavlou, A. K., and J. M. Reichert. 2004. Recombinant protein therapeutics-success rates, market trends and values to 2010. Nat. Biotechnol. 22: 1513-1519.
Pearson, S. 2007. Boosting use of microbial systems in manufacturing. Genetic engineering news. 27: 1, 45-47.
Petersen, C. 1998. Inhibition of cellular growth by increased guanine nucleotide pools. J. Biol. Chem. 274: 5348-5356.
Petersen, C., and L. B. Moller. 2000. Invariance of the nucleotide triphosphate pools of Escherichia coli with growth rate. J. Biol. Chem. 275: 3931-393.
Pyo, S. H., J. H. Lee, H. B. Park, S. S. Hong, and J. H. Kim. 2001. A large-scale purification of recombinant histone H1.5 from Escherichia coli. Protein Expr. Purif. 23: 38–44.
Phumathon, P., and G. M. Stephens. 1999. Production of toluene cis-glycol using recombinant Escherichia coli strains in glucose-limited fed-batch culture. Enzyme Microb. Technol. 25: 810-819.
Riesenberg, D., and R. Guthke. 1999. High-cell-density cultivation of microorganisms. Appl. Microbiol. biotechnol. 51: 422-430.
Saier M. H., T. M. Ramseier, and J. Reizer. 1996. Regulation of carbon utilisation. 1325-1343. In F. C. Neidhardt (ed.), Escherichia coli and Salmonella: cellular and molecular biology, 2nd ed., vol. 1. ASM Press, Washington, D. C.
Sakamoto, S., M. Iijima, H. Matsuzawa, and T. Ohta. 1994. Production of thermophilic protease by glucose-controlled fed-batch culture of recombinant Escherichia coli. J. Ferment. Bioeng. 78: 304-309.
Schneider, D. A., and R. L. Gourse. 2004. Relationship between growth rate and ATP concentration in Escherichia coli. J. Biol. Chem. 279:8262–8268.
Schreiber, G., S. Metzger, E. Aizenman, S. Roza, M. Cashel, and G. Glaser. 1991. Overexpression of the relA gene in Escherichia coli. J. Biol. Chem. 266: 3760-3767.
Seyfzadeh, M., J. Keener, and M. Nomura. 1993. spoT-dependent accumulation of guanosine tetraphosphate in response to fatty acid starvation in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 90: 11004-11008.
Shimizu, M., S. Iijima, and T. Kobayashi. 1992. Production of insecticidal protein of Bacillus thuringiensis by cultivation of recombinant Escherichia coli. J. Ferment. Bioeng. 74: 163-168.
Shiloach, J., J. Kaufman, A. S. Guillard, and R. Fass. 1996. Effect of glucose supply strategy on acetate accumulation, growth, and recombinant protein production by Escherichia coli BL21 (λDE3) and Escherichia coli JM109. Biotechnol. Bioeng. 49: 421-428.
Slattery, D. M., D. A. Waltz, B. Denham, M. O'Mahony, and P. Greally. 2001. Bronchoscopically administered recombinant human DNase for lobar atelectasis in Cystic fibrosis. Pediatr. Pulmonol. 31: 383-388.
Smith, M. A., and M. J. Bidochka. 1998. Bacterial fitness and plasmid loss: the importance of culture conditions and plasmid size. Can. J. Microbiol. 44: 351-355.
Svitil, A. L., M. Cashel, and J. W. Zyskind. 1993. Guanosine tetraphosphate inhibits protein synthesis in vivo. J. Biol. Chem. 268: 2307-2311.
Sy, J. 1977. In vitro degradation of guanosine 5’-diphosphate, 3’-diphosphate. Proc. Natl Acad. Sci. USA. 74: 5529-5533.
Teich, A., S. Meyer, H. Y. Lin, L. Andersson, S.-O. Enfors, and P. Neubauer. 1999. Growth rate related concentration changes of the starvation response regulators σS and ppGpp in glucose-limited fed-batch and continuous cultures of Escherichia coli. Biotechnol. Prog. 15: 123-129.
Ten Berge, M., G. Brinkhorst, A. A. Kroon, and J. C. de Jongste, 1999. DNase treatment in primary ciliary dyskinesia assessment by nocturnal pulse oximetry. Pediatr. Pulmonol. 27: 59-61.
Turner, C., M. E. Gregory, and M. K. Turner. 1994. A study of the effect of specific growth rate and acetate on recombinant protein production of Escherichia coli JM107. Biotechnol. Lett. 16: 891-896.
Ueguchi, C., N. Misonou, and T. Mizuno. 2001. Negative control of ropS expression by phosphoenolpyruvate: carbohydrate phosphotransferase system in Escherichia coli. J. Bacteriol. 183: 520-527.
Vind, J., M. A. Sorensen, M. D. Rasmussen, and S. Pedersen. 1993. Synthesis of protein in Escherichia coli is limited by the concentration of free ribosomes. J. Mol. Biol. 231: 678-688.
Voellmy, R., and A. L. Goldberg. 1980. Guanosine-5’-diphosphate-3’-diphosphate (ppGpp) and the regulation of protein breakdown in Escherichia coli. J. Biol. Chem. 255: 1008-1014.
Walker-Simmons, M., and D. E. Atkinson. 1977. Functional capacities and the adenylate energy charge in Escherichia coli under conditions of nutritional stress. J. Bacteriol. 130: 676-683.
Walsh, G. 2003. Biopharmaceuticals: Biochemistry and Biotechnology. 2nd ed. J. Wiley & Sons, Ltd. New York.
Wang, F., and S. Y. Lee. 1998. High cell density culture of metabolically engineered Escherichia coli for the production of poly(3-hydroxybutyrate) in a defined medium. Biotechnol. Bioeng. 58: 325-8.
Wendrich, T. M., G. Blaha, D. N. Wilson, M. A. Marahiel, and K. H. Nierhaus. 2002. Dissection of the mechanism for the stringent factor RelA. Mol. Cells. 10: 779–788.
Wong, I., A. Hernandez, M. A. Garca, R. Segura, and I. Rodrguez. 2002. Fermentation scale up for recombinant K99 antigen production cloned in Escherichia coli MC1061 I. Process Biochem. 37: 1195-1199.
Yang, X.-M., L. Xu, and L. Eppstein. 1992. Production of recombinant human interferon-α1 by Escherichia coli using a computer-controlled cultivation process. J. Biotechnol. 27: 291-301.
Yee, L., and H. W. Blanch. 1992. Recombinant protein expression in high cell density fed-batch cultures of Escherichia coli. Bio/Technology. 10: 1550-1556.
Zabriskie, D. W., and E. J. Arcuri. 1986. Factors influencing productivity of fermentations employing recombinant microorganisms. Enzyme Microb. Technol. 8: 706-717.
Zwietering, M. H., I. Jongenburger, F. M. Rombouts, and K. VAN 'T Riet. 1990. Modeling of the bacterial growth curve. Appl. Environ. Microbiol. 56: 1875-1881.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊
 
系統版面圖檔 系統版面圖檔