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dc.contributor.authorChou, Hsiao-Yien_US
dc.identifier.citation1.甘淑貞。 2002. P-450 Monooxygenase、P-450 Reductase及Redoxin基因的選殖、表現及其對轉換Compaction成Pravastation時的應用。碩士論文,分子生物學研究所,中興大學,台中。 2.田蔚城。1999。生物產業與製藥產業。九州圖書。台北市。 3.林郁君。2008。酮基還原酵素之篩選俾應用於L-phenylephrine之生產。 碩士論文,分子生物學研究所,中興大學,台中。. 4.徐人英。1975。藥物化學。合記圖書出版社。台北市。 5.許桂森。2002。簡明圖解藥理學。藝軒圖書。台北市。 6.陳俊彰。2002。 Aspergillus oryzae 與 Aspergillus sojae leucine aminopeptidase 基因的調控。碩士論文,分子生物學研究所,中興大學,台中。 7.陳建宇。2009。Rhodococcus spp. aminoketone reductase 之基因選殖、特性分析及其應用於phenylephrine之生產。碩士論文,分子生物學研究所,中興大學,台中。 8.陳慧中。2006。酮基還原酵素之篩選俾應用於L-phenylephrine之生合成。 碩士論文,分子生物學研究所,中興大學,台中。 9.傅則凱。2009。選殖Serratia菌屬之ketone reductase得將HPMAE轉換成L-phenylephrine。碩士論文,分子生物學研究所,中興大學,台中。 10.潘志龍。1997。 Corynebacterium glutamicum DHAP Synthase與Prephenate Dehydratase之間的蛋白質交互作用。碩士論文,分子生物學研究所,中興大學,台中。 11.Ang-Kucuker, M., O. Buyukbaba-Boral, V. Tolun, D. Torumkuney, S. Susever, and O. Ang. 2000. Effect of some antibiotics on pigmentation in Serratia marcescens. Zentralbl Bakteriol 289:781-5. 12.Anita Khanafari, M. M. A., and Fatemeh Ahmadi Fakhr 2006. Review of Prodigiosin, Pigmentation in Serratia marcescens Biological Sciences. 6(1):1-13 13.Conway T, S. G., Osman YA, Ingram LO. 1987 Cloning and sequencing of the alcohol dehydrogenase II gene from Zymomonas mobilis. J Bacteriol 169(6):2591-7. 14.Csuk, R. 1991. Baker''s yeast mediated transformations in organic chemistry. Chem Rev 91:49-97. 15.Ding, M. J., and R. P. Williams. 1983. Biosynthesis of prodigiosin by white strains of Serratia marcescens isolated from patients. J Clin Microbiol 17:476-80. 16.Erlich, H. A. 1989. PCR technology: principles and applications for DNA amplification. Stockton Press. 17.Ford, G., and E. M. Ellis. 2001. Three aldo-keto reductases of the yeast Saccharomyces cerevisiae. Chem Biol Interact 130-132:685-98. 18.Fuchs, R. L., S. A. McPherson, and D. J. Drahos. 1986. Cloning of a Serratia marcescens Gene Encoding Chitinase. Appl Environ Microbiol 51:504-9. 19.Gal, S. W., J. Y. Choi, C. Y. Kim, Y. H. Cheong, Y. J. Choi, J. D. Bahk, S. Y. Lee, and M. J. Cho. 1997. Isolation and characterization of the 54-kDa and 22-kDa chitinase genes of Serratia marcescens KCTC2172. FEMS Microbiol Lett 151:197-204. 20.Gal, S. W., J. Y. Choi, C. Y. Kim, Y. H. Cheong, Y. J. Choi, S. Y. Lee, J. D. Bahk, and M. J. Cho. 1998. Cloning of the 52-kDa chitinase gene from Serratia marcescens KCTC2172 and its proteolytic cleavage into an active 35-kDa enzyme. FEMS Microbiol Lett 160:151-8. 21.Gilman, A. G., Goodman, L.S., Hardman, J.G., and Limbird, L.E. 2001. Goodman & Gilman''s the pharmacological basis of therapeutics. McGraw-Hill, New York, N.Y. 22.Havel, J., and D. Weuster-Botz. 2006. Comparative study of cyanobacteria as biocatalysts for the asymmetric synthesis of chiral building blocks. Eng. Life Sci. 6:175-179. 23.Hejazi, A., and F. R. Falkiner. 1997. Serratia marcescens. J Med Microbiol 46:903-12. 24.Hoffmann, F., and E. Maser. 2007. Carbonyl reductases and pluripotent hydroxysteroid dehydrogenases of the short-chain dehydrogenase/reductase superfamily. Drug Metab Rev 39:87-144. 25.Holsch, K., J. Havel, M. Haslbeck, and D. Weuster-Botz. 2008. Identification, cloning, and characterization of a novel ketoreductase from the cyanobacterium Synechococcus sp. strain PCC 7942. Appl Environ Microbiol 74:6697-702. 26.Jones, J. D., K. L. Grady, T. V. Suslow, and J. R. Bedbrook. 1986. Isolation and characterization of genes encoding two chitinase enzymes from Serratia marcescens. EMBO J 5:467-73. 27.Jornvall, H., B. Persson, M. Krook, S. Atrian, R. Gonzalez-Duarte, J. Jeffery, and D. Ghosh. 1995. Short-chain dehydrogenases/reductases (SDR). Biochemistry 34:6003-13. 28.Kabashima, T., A. Kitazono, A. Kitano, K. Ito, and T. Yoshimoto. 1997. Prolyl aminopeptidase from Serratia marcescens: cloning of the enzyme gene and crystallization of the expressed enzyme. J Biochem 122:601-5. 29.Kataoka, M., K. Kita, M. Wada, Y. Yasohara, J. Hasegawa, and S. Shimizu 2003. Novel bioreduction system for the production of chiral alcohols. Appl. Microbiol. Biotechnol. 62:437-445. 30.Kataoka, M., Nakamura, Y., Urano, N.,Ishige, T., Shi, G., Kita, S., Shimizu, S. 2006. A novel NADP+-dependent L-1-amino-2-propanol dehydrogenase from Rhodococcus erythropolis MAK154: a promising enzyme for the production of double chiral aminoalcohols Lett Appl Microbiol 43:430-435. 31.Kataoka, M., T., Ishige, N., Urano, Y., Nakamura, E., Sakuradani, S., Fukui, S., Kita, K., Sakamoto, and S., Shimizu. 2008. Cloning and expression of the L-1-amino-2-propanol dehydrogenase gene from Rhodococcus erythropolis, and its application to double chiral compound production. Appl. Microbiol. Biotechnol. 80:597-604. 32.Kwon, M. A., H. S. Kim, J. Y. Oh, B. K. Song, and J. K. Song. 2009. Gene cloning, expression, and characterization of a new carboxylesterase from Serratia sp. SES-01: comparison with Escherichia coli BioHe enzyme. J Microbiol Biotechnol 19:147-54. 33.Laemmli, U. K. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680-5. 34.Lee, K. W., H. A. Bae, and Y. H. Lee. 2007. Molecular cloning and functional expression of esf gene encoding enantioselective lipase from Serratia marcescens ES-2 for kinetic resolution of optically active (S)-flurbiprofen. J Microbiol Biotechnol 17:74-80. 35.Li, X., S. Tetling, U. K. Winkler, K. E. Jaeger, and M. J. Benedik. 1995. Gene cloning, sequence analysis, purification, and secretion by Escherichia coli of an extracellular lipase from Serratia marcescens. Appl Environ Microbiol 61:2674-80. 36.Lillie, R. D. 1977. H. J. Conn''s biological stains, 9th ed., The Williams & Wilkins Co., Baltimore. 37.Moore, J. C., D. J. Pollard, B. Kosjek, and P. N. Devine. 2007. Advances in the enzymatic reduction of ketones. Acc Chem Res 40:1412-9. 2005. Drug companies consider substitute for cold medicine. McMinnville, Oregon. 39.Nomura, C. T., K. Taguchi, Z. Gan, K. Kuwabara, T. Tanaka, K. Takase, and Y. Doi. 2005. Expression of 3-ketoacyl-acyl carrier protein reductase (fabG) genes enhances production of polyhydroxyalkanoate copolymer from glucose in recombinant Escherichia coli JM109. Appl Environ Microbiol 71:4297-306. 40.Olsen, K. W., D. Moras, and M. G. Rossmann. 1975. Sequence variability and structure of D-glyceraldehyde-3-phosphate dehydrogenase. J Biol Chem 250:9313-21. 41.Pang, Y., W. Q. Song, F. Y. Chen, and Y. M. Qin. 2010. A new cotton SDR family gene encodes a polypeptide possessing aldehyde reductase and 3-ketoacyl-CoA reductase activities. Biochemistry (Mosc) 75:320-6. 42.Persson, B., Y. Kallberg, U. Oppermann, and H. Jornvall. 2003. Coenzyme-based functional assignments of short-chain dehydrogenases/reductases (SDRs). Chem Biol Interact 143-144:271-8. 43.Raeder, U., and P. Broda. 1985. Rapid preparation of DNA from filamentous fungi. Lett. Appl. Microbiol 1:17-20. 44.Ren, Q., N. Sierro, B. Witholt, and B. Kessler. 2000. FabG, an NADPH-dependent 3-ketoacyl reductase of Pseudomonas aeruginosa, provides precursors for medium-chain-length poly-3-hydroxyalkanoate biosynthesis in Escherichia coli. J Bacteriol 182:2978-81. 45.Sambrook, J., and D. W. Russell. 2006. The condensed protocols from Molecular cloning : a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. 46.Singleton, P., and D. Sainsbury. 2001. Dictionary of Microbiology and Molecular Biology. Johan Willy and Sons Ltd, 3rd Edn.. 47.Williams, R. P. 1973. Biosynthesis of prodigiosin, a secondary metabolite of Serratia marcescens. Appl Microbiol 25:396-402. 48.Zelinski, T., and M. R. Kula. 1994. A kinetic study and application of a novel carbonyl reductase isolated from Rhodococcus erythropolis. Bioorg Med Chem 2:421-8. 49.Zelinski, T., J. Peters, and M. R. Kula. 1994. Purification and characterization of a novel carbonyl reductase isolated from Rhodococcus erythropolis. J Biotechnol 33:283-92.zh_TW
dc.description.abstractL-form phenylephrine (L-PE) is an effectively decongestant and commonly incorporated into cold and allergy drugs. The gene encoding a protein with ketone reductase activity was cloned for the asymmetric synthesis of L-PE from its precursor, 2-[benzyl(methyl)amino]-1-(3-hydroxyphenyl) ethanone (BMAHPE) and 1-(3-hydroxyphenyl)-2-(methylamino) ethanone (HPMAE). Both D-form and L-form of 3-{(1S)-2-[benzyl(methyl)amino]-1- hydroxyphenyl}phenol (BMA-PE) was prepared by chemical synthesis for the chirarity of the BMA-PE from bioconversion . It was founded that the BMA-PE from S. marcescens BCRC10948 was L-form. Inducer, the 2-phenylethanol、acetophenone and 1-phenylethanol were added in the culture medium of S. marcescens BCRC10948 for the conversion of HPMAE to PE, and the conversion ratio was 78.6 % ,77.5 % , and 73.2 % were obtained,respectively. Ribosyldihydronicotinamide dehydrogenase 1 from the genomic library of S. marcescens BCRC10948 could convert BMAHPE to BMA-PE with conversion ratio of 0.0094 % in the reaction mixture containing 5 mM BMAHPE, 0.1 M Na-phosphate buffer (pH 7.0) and 2 % glucose at 30℃ for 24 h. AKR7-2(aldo-keto reductase)、ADH3(alcohol dehydrogenase)、SMR 3(reductase)、SMR 44 and SMR 48 also possesed the enzymatic activity to convert BMAHPE to BMA-PE with conversion ratio below 0.013 %. Two gene product, SDR72 and SDR10 , showed capability of converting the HPMAE to D-PE and L-PE, respectively, with conversion ratio was 83 % and 68 % in the reaction mixture containing 10 mM HPMAE, 0.1 M sodium phosphate buffer (pH 7.0) and 2 % glucose at 30℃ for 24 h. It is the first reported that L-PE could be converted from HPMAE by SDR10 enzyme from S. marcescens BCRC10948.zh_TW
dc.description.abstractL-form phenylephrine(L-PE;苯腎上腺素)為一化學合成藥物,屬於不對稱化合物(chiral compound),廣泛的添加於感冒藥及抗過敏藥物中。本研究擬選殖能將2-[benzyl(methyl)amino]-1-(3-hydroxyphenyl) ethanone (BMAHPE) 轉換成L-form 3-{(1S)-2-[benzyl(methyl)amino]-1- hydroxyphenyl}phenol (BMA-PE)的基因或將1-(3-hydroxyphenyl)-2-(methylamino) ethanone (HPMAE) 轉換成L-PE的基因,進而利用微生物催化方式生產L-PE。本研究先利用化學法合成D-form及L-form的BMA-PE標準品,並使用Cyclobond I 2000 AC管柱分析,證實Serratia marcescens BCRC10948能將BMAHPE轉換成L-form BMA-PE及將HPMAE轉換成L-PE。當在培養基內加入2-phenylethanol、acetophenone及1-phenylethanol時,菌體對HPMAE的轉換率會從21.3 % 提升到78.6 %、77.5 % 及73 %。在S. marcescens BCRC10948基因庫中,發現ribosyldihydronicotinamide dehydrogenase 1基因之產物具有轉換BMAHPE的活性,惟在含有5 mM BMAHPE、0.1 M sodium phosphate buffer (pH 7.0)及2 % glucose反應液內,30℃反應24小時後,轉換率只有0.0094 %。在S. marcescens dehydrogenase及reductase基因產物中,AKR7-2(aldo-ketone reductase)、ADH3(alcohol dehydrogenase)、SMR 3、SMR 44及SMR 48具有轉換BMAHPE成BMA-PE的活性,轉換率最高為0.013 % 。在轉換HPMAE成PE部分,發現基因產物SDR72及SDR10具有轉換活性,其分子量分別為29 kDa及27.5 kDa,在含有10 mM HPMAE、0.1 M Na-phosphate buffer (pH 7.0)及2 % glucose、30℃反應24小時後,轉換率分別為83 % 及68 %, SDR72的轉換產物為D-PE,而SDR10的轉換產物為L-PE。本研究結果顯示SDR10能將HPMAE轉換為L-PE,為首次發現可將HPMAE轉換成L-PE的基因,在工業應用上有其潛力,在基礎研究上也有其價值。zh_TW
dc.description.tableofcontents目錄------------------------------------------------------Ⅰ 表目錄----------------------------------------------------IV 圖目錄-----------------------------------------------------V 摘要-----------------------------------------------------VII 英文摘要------------------------------------------------VIII 縮寫對照表------------------------------------------------IX 前言 (一)研究背景-----------------------------------------------1 (二)研究目的-----------------------------------------------1 前人研究 (一)不對稱還原反應與生物催化反應---------------------------3 (二)Serratia 菌屬之特性與應用------------------------------3 (三)AKR與SDR superfamily ----------------------------------4 (四)能將BMAHPE轉換成BMA-PE或將HPMAE轉換成PE之菌株----------4 (五)研究策略-----------------------------------------------5 材料與方法 (一)藥品-------------------------------------------------6 (二)菌株、質體與培養基-----------------------------------6 (三)BMA-PE單一旋光性標準品之合成-------------------------6 (四)高效能液相層析 (High performance liquid chromatography, HPLC)分析----7 (五)誘導實驗---------------------------------------------7 (六)基因選殖、表現與活性分析-----------------------------8 (七)S. marcescens染色體基因庫---------------------------10 結果 一、BMAHPE的生物轉換 (一)篩選能將BMAHPE轉換成BMA-PE的菌株--------------------11 (二)利用菌體將BMAHPE轉換成BMA-PE------------------------11 (三)BMA-PE 之chirarity分析------------------------------12 (四)誘導物測試------------------------------------------12 (五)S. cerevisiae BCRC50407的aldo-keto reductase 基因選殖與表現----------------------------------------------------13 (六)利用洋菜平板培養基篩選能轉換BMAHPE的菌株------------13 (七)S. marcescens BCRC10948基因庫的建構-----------------13 (八)S. marcescens BCRC10948的reductase及alcohol dehydrogenase基因之選殖及表現-----------------------------14 (九)篩選S. marcescens BCRC10948的reductase及alcohol dehydrogenase基因其能轉換BMAHPE成BMA-PE-------------------15 二、HPMAE的生物轉換 (一)誘導物測試------------------------------------------15 (二)篩選S. marcescens BCRC10948的reductase及alcohol dehydrogenase基因其能轉換HPMAE成PE------------------------16 討論 (一)誘導物------------------------------------------------17 (二)轉換HPMAE成PE之基因-----------------------------------17 (三)轉換BMAHPE成BMA-PE之基因------------------------------19 (四)洋菜平板篩選法----------------------------------------19 結論 -----------------------------------------------------21 參考文獻 -------------------------------------------------63 附錄 -----------------------------------------------------67zh_TW
dc.subjectSerratia marcescensen_US
dc.subjectketone reductaseen_US
dc.title利用Rhodosporidium toruloides BCRC 21888 及 Serratia marcescens BCRC10948做為生物催化劑生產L-phenylephrinezh_TW
dc.titleProduction of L-phenylephrine using Rhodosporidium toruloides BCRC 21888 and Serratia marcescens BCRC10948 as biocatalystsen_US
dc.typeThesis and Dissertationzh_TW
item.openairetypeThesis and Dissertation-
item.fulltextno fulltext-
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