Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/21886
標題: Screening of the ketone reductase for L-phenylephrine production
酮基還原酵素之篩選俾應用於L-phenylephrine之生產
作者: Lin, Yu-Chun
林郁君
關鍵字: ketone reductase;酮基還原酵素;phenylephrine;AKR;short-chain dehydrogenase;asymmetric reduction;類腎上腺素藥物;苯腎上腺素;不對稱性合成
出版社: 分子生物學研究所
引用: 參 考 文 獻 1. 徐人英。1975。藥物化學。合記圖書出版社,台北市。 2. 王立禾, 阮立昂譯。1977。蛋白質構造與功能。復漢出版社。 3. 金明儒。1980。有機藥物化學。財團法人中華藥學研究基金會,台北市。 4. 李澤維。1981。最新藥物化學,第五版。南山堂,台北市。 5. 秦道堅。1982。近代有機藥物化學。維新書局,台北市。 6. 潘志龍。1997。Corynebacterium glutamicum DHAO 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。 7. 何子樂。1998。科學月刊,第345期。 8. 田蔚城。1999。生物產業與製藥產業。九州圖書,台北市。 9. 何子樂。2001。發現月刊,第56期。 10. 許桂森。2002。簡明圖解藥理學。藝軒圖書,台北市。 11. 華北製藥集團公司。2002。中國醫藥經貿網:http://www.ncpc.com.cn/news/, 河北省。 12. 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。 13. 陳怡潔。2003。以離胺酸消旋酵素基因作為基因選殖的篩選標記。碩士論文,分子生物學研究所,中興大學,台中。 14. 吳昭燕。2003。科學發展,第370期。 15. 羅雪霞。2004。利用新的酵素法生產L-Homophenylalanine。博士論文,分子 生物學研究所,中興大學,台中。 16. 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。 17. Antunes, H., Fardelone, L. C., Rodrigues, J. A. R., Moran, P. J. S. 2004. Bioreduction of 2-azido-1-arylethanones mediated by Geotrichum candidum and Rhodotorula glutinis. Tetrahedron: Asymmetry. 15: 2615–2620. 18. Aiying, L., Takayuki, I., Takaaki, T., Ting, X., Yutaka, E. and Koji, I. 2005. Functional studies on a ketoreductase gene from Streptomyces sp. AM-7161 to control the stereochemistry in medermycin biosynthesis. Bioorg. Med. Chem. 13: 6856–6863. 19. Barbieri, C., Caruso, E., D’Arrigo, P., Fantoni, G. P. And Servi, S. 1999. Tetrahedron: Asymmetry. 1 : 3931–3937. 20. Conceição, G. J. A., Moran, P. J. S., and Rodrigues, J. A. R. 2003. Chemoenzymatic syntheses of (R)-2-bromo-, (R)2-chloro- and (R)2-azido-1- (1,3-benzodioxol-5-yl)-1-ethanol. ARKIVOC. 10: 500–506. 21. Dorokhova, M. I., Somelina, N. E., Tikhonova, O. Ya. and Mikhalev, V. A. 1974. Nversion of configuration of optically active 1-m-nitrophenyl-2- methylamino ethanols. Pharm. Chem. J. 8: 209-211. 22. David J. P. and John M. W. 2007. Biocatalysis for pharmaceutical intermediates: the future is now. Trends in Biotechnol. 25(2): 66-73. 23. Erlich, H. A. 1989. PCR technology: principles and applications for DNA amplification. Stockton Press, New York, N.Y. 24. Gilman, A.G., Goodman, L.S., Hardman, J.G., and Limbird, L.E. 2001. Goodman & Gilman''s the pharmacological basis of therapeutics, 10th ed. McGraw-Hill, New York, N.Y. 25. Hummel, W. and Kula, M.R.. 1989. Dehydrogenases for the synthesis of chiral compounds. Eur. J. Biochem. 184, 1 – 13. 26. Homann, M. J., Vail, R. B., Previte, E., Tamarez, M., Morgan, B., Dodds, D. R. and Zaks,A. 2004. (2S)-2-Anilinomethylpyrrolidine: an efficient in situ recyclable chiral catalytic source for the borane-mediated asymmetric reduction of prochiral ketones in refluxing toluene.Tetrahedron. 60: 789–797. 27. Jörnvall H, et. al. 1995. Short-chain dehydrogenases/reductases (SDR). Biochemistry, 34: 6003-6013. 28. Jones DT. 1999. Protein secondary structure prediction based on position-specific scoring matrices. J. Mol. Biol. 292: 195-202. 29. Jornvall, H., Hoog, J.-O., and Persson, B. 1999. SDR and MDR: Completed genome sequences show these protein families to be large, of old origin, and of complex nature. FEBS Lett. 445: 261–264. 30. Joanna, D. M., Peter, P. F., James, P. F. and Carl E. C. 2003. Regio- and Stereoselective Metabolism of 7,12-Dimethylbenz[a]anthracene by Mycobacterium vanbaalenii PYR-1. Appl. Environ. Microbiol. 69 (7): 3924–3931. 31. J. Augusto R. Rodrigues, Paulo J. S. Moran, Gelson J. A. Conceição and Lucídio C. Fardelone. 2004. Recent Advances in the Biocatalytic Asymmetric Reduction of Acetophenones and α,β-Unsaturated Carbonyl Compounds. J. A. R. RODRIGUES et al.: Asymmetric Reduction of Carbonyl Compounds, Food Technol. Biotechnol. 42 (4): 295–303. 32. Joanna, D. M., James, P. F., Peter, P. F. and Carl, E. C. 2004. Degradation of Benzo[a]pyrene by Mycobacterium vanbaalenii PYR-1. Appl. Environ. Microbiol. 70 (1): 340-345. 33. Klinger, F. D. 2001. Method for Preparing of L-Phenylephrine Hydrochloride. US Patent 6187956 B1. 34 Kataoka, M., Kita, K., Wada, M., Yasohara, Y., Hasegawa, J. and Shimizu, S. 2003. Novel bioreduction system for the production of chiral alcohols. Appl. Microbiol. Biotechnol. 62: 437-445. 35. Kaoru, N.*, Rio, Y. A. Tomoko, M. and Tadao H. 2003. Recent developments in asymmetric reduction of ketones with biocatalysts. Tetrahedron: Asymmetry 14: 2659–2681. 36. Kousuke, I,, Yoshihide, M,, and Nobuya, I. 2005. Purification and characterization of a novel alcohol dehydrogenase from Leifsonia sp. Strain S749: a promising biocatalyst for an asymmetric hydrogen transfer bioreduction. Appl. Environ. Microbiol. 3633–3641. 37. Loyd, V., Allen, Jr., Berardi, R. R. 2002. Handbook of nonprescription drugs, 13th ed. Apha Publications, Washington, DC. 38. Lucídio C. Fardelone, J. Augusto R. Rodrigues, and Paulo J. S. Moran. 2003. Bioreduction of α-haloacetophenones by Rhodotorula glutinis and Geotrichum candidu. ARKIVOC , 404-410. 39. Moran, P. J. S., Fardelone, L. C., and Rodrigues, J. A. R. 2003. BR Patent PI 0303790–8. 40. News-register.com. 2005. Durg companies consider substiture for cold medicine, McMinnville, Oregon. 41. Ohgew, K., Seong, J. K., Richard, C. J., James, P. F. Michael, D. A., Ricky, D. E. and Carl, E. C. 2007. A Polyomic Approach To Elucidate the Fluoranthene-Degradative Pathway in Mycobacterium vanbaalenii PYR-1. J. Bacteriol. 189 (13): 4635–4647. 42. Patel, R. N. 2001. Biocatalytic synthesis of intermediates for the synthesis of chiral drug substances. Curr. Opin. Biotechnol. 12: 587-604. 43. Reiji, M., Mikio, N., Yasushi, I., Seiji, I,. and Masami, I. 2002. The enzymes with benzil reductase activity conserved from bacteria to mammals. J. Biotechnol. 94: 157–169. 34. Robin, L. Stingley, B. B., Ashraf A. K. and Carl E. C. 2004. Novel organization of genes in a phthalate degradation operon of Mycobacterium vanbaalenii PYR-1. Microbiology. (150: 3749–3761. 45. Sambrook, J., Fritsch, E.F. and Maniatis, T. 1989. Molecular cloning: a labratory manual. Cold Spring Harbor Labratory, New York, N.Y. 46. Sakamoto, K. 2004. Aminoketone asymmetric reductase and nucleic acid thereof. US 20040247583 A1. 47. Seong, J. K., Ohgew, K., James, P. F., Richard, C. J., Michael, D. A., Jin, W. J., Ricky, D. E. and Carl, E. C. 2006. Molecular cloning and expression of genes encoding a novel dioxygenase involved in low- and high-molecular-weight polycyclic aromatic hydrocarbon degradation in Mycobacterium vanbaalenii PYR-1. Appl. Environ. Microbiol. 72 (2): 1045–1054. 48. Seong, J, K., Ohgew, K., Richard, C. J., James, P. F., Ricky, D. E. and Carl, E. C. 2007. Complete and Integrated Pyrene Degradation Pathway in Mycobacterium vanbaalenii PYR-1 Based on Systems Biology. J. Bacteriol. 189 (2): 464–472. 49. Udo, O., Charlotta, F., Malin, H., Naeem, S., Xiaoqiu, W., Monica L., Jawed, S., Erik, N.., Yvonne, K., Bengt, P., Hans, J. 2003. Short-chain dehydrogenases/reductases (SDR): the 2002 update. Chem. Biolo. Interactions. 247-253 50. Urano, N., Kataoka, M., Nakamura, Y., Ishige, T., Shi, G., Kita, S., Sakamoto, K., and 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. The Society for Applied Microbiology. 43: 430–435. 51. Yvonne, K., Oppermann, U., Jörnvall, H. and Persson, B. 2002. Short-chain dehydrogenase/reductase (SDR) relationships: a large family with eight clusters common to human, animal, and plant genomes.Protein Sci. 11: 636-641. 52. Ye N., Jian, H. U. 2002. Asymmetric reduction of aryl ketones with a new isolate Rhodotorula sp. AS2.2241. J. Mol. Catal. B: Enzym. 18: 233–241. 53. Yukari, S., Marta, M., Radka C., Zbynˇek, P., Yoshiyuki, O., Kiwamu, M., Masataka, T., Jirˇı´ D. and Yuji, N. 2005. Two rhizobial strains, Mesorhizobium loti MAFF303099 and Bradyrhizobium japonicum USDA110, encode haloalkane dehalogenases with novel structures and substrate specificities. Appl. Environ. Microbiol. 71 (8): 4372–4379 . 54. Yong, M. Q., Francois, M. P., Yong, H. S., Jian, X. F., Yi, M. L., Alexander, J. K., J, K. H. and Yu, X. Z. 2005. Cloning and functional characterization of two cDNAs encoding NADPHdependent 3-ketoacyl-CoA reductased from developing cotton fibers. Cell Res. 15(6):465-473. 55. Qing, C., Terry, A., Theresa, M. and Mark, P. 2007. Functional studies of aldo-keto reductases in Saccharomyces cerevisiae. Biochimica et Biophysica Acta 1773: 321–329. 56. Xiang, L., Zhijie, F., Jianhe, X. 2006. Asymmetric reduction of aromatic ketones with yeast cells. Chin. Jour. Cata. 27, 1. 57. Zhi, L., Jie, Z., Wouter, A. And Duetz, B. Wi. 2004. Rapid identification of new bacterial alcohol dehydrogenases for (R)- and (S)-enantioselective reduction of ß-ketoesters. Chem . Commun . 2 1 2 0 – 2 1 2 1 58. Itoh, N., Matsuda, M., Mabuchi, M., Dairi, T. and Wang, J. 2002. Chiral alcohol production by NADH-dependent phenylacetaldehyde reductase coupled with in situ regeneration of NADH. Eur. J. Biochem. 269, 2394-2402.
摘要: 
L-Phenylephrine (L-PE) 為人工合成的化學藥物,目前廣泛被添加在感冒藥及抗過敏藥物中的一種腎上腺素藥物(adrenergic drugs)。其藥性與麻黃(Ephedra)相似,但因結構上的不同,對於心血管系統與中樞神經系統的刺激較低且副作用較少,因此在醫藥市場上的需求逐漸向上提升以取代麻黃。目前L-PE的生產仍是以化學法來進行,為了節省化學法所需的繁雜步驟及降低其合成的危險性,因此希望能以微生物轉換法來進行L-PE的合成。本研究的主要目的在於篩選具有ketone reductase活性的微生物或酵素,將前驅物1-(3-hydroxyphenyl)- 2-(methylamino) ethanone (HPMAE)及2-[benzyl(methyl)amino]-1-(3-hydroxyphenyl) ethanone (BMAHPE)不對稱還原成PE與3-{(1S)-2-[benzyl(methyl)amino]-1-hydroxyethyl} phenol (BMA-PE)。利用微生物全菌體酵素反應,以高效能液相層析法(HPLC)進行分析,發現Strepotmyces thermovulgaris BCRC 12488與Mycobacterium sp. NCHU-1,分別具有將HPMAE轉換成D-PE及L-PE的酵素活性;而Rhodotorula gracilis BCRC 21888與Rhodosporidium toruloides BCRC 21374則具有將BMAHPE轉換成BMA-PE的活性。將Mycobacterium sp. NCHU-1之sdr基因以E.coli NovaBlue (pQE30-SDR)及E. coli BL21(DE3) (pET32a-SDR)進行表現,卻不具有轉換HPMAE的能力。

L-Phenylephrine (L-PE) is a chemical compound of pharmaceutical importance which is synthesized by chemical method. It mainly acts as a decongestant and as anti-allergic and is used commonly for cold. The pharmaceutical property of L-PE is similar to ephedrine; but due to their different chemical structure, L-PE has very less incitant and side effect to the cardiovascular system and the central nervous system. Thus the demand for L-PE in the drug industry is growing up progressively in the place of ephedrine. In the present situations, L-PE is still produced by chemical synthesis. In order to avoid multifarious and complicated processes involved in the chemical synthesis method, the present study was designed to use biotransformation approach to produce L-PE. The main purpose of the study is to screen a novel microorganism or an enzyme with ketone reductase activity for asymmetric synthesis PE and 3-{(1S)-2-[benzyl(methyl)amino] -1-hydroxyethyl} phenol (BMA-PE) from its precursor, 1-(3-hydroxyphenyl)-2- (methylamino) ethanone (HPMAE) and 2-[benzyl(methyl)amino]-1-(3-hydroxyphenyl) ethanone (BMAHPE). We discovered the whole cells of that Strepotmyces thermovulgaris BCRC 12488 and Mycobacterium sp. NCHU-1 had the enzymatic activity to convert HPMAE to D-PE and L-PE, respectively. Rhodotorula gracilis BCRC 21888 and Rhodosporidium toruloides BCRC 21374 were found to possess the enzymatic activity to convert BMAHPE to BMA-PE. Cloning of short-chain dehydrogenase/reductase (sdr) from Mycobacterium sp. NCHU-1 and its expression in Escherichia coli NovaBlue (pQE30-SDR) and E. coli BL21(DE3) (pET32a-SDR), revealed the lack of ability of sdr to convert HPMAE.
URI: http://hdl.handle.net/11455/21886
其他識別: U0005-2901200814062600
Appears in Collections:分子生物學研究所

Show full item record
 

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.