Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/22101
標題: 利用Rhodosporidium toruloides BCRC 21888 及 Serratia marcescens BCRC10948做為生物催化劑生產L-phenylephrine
Production of L-phenylephrine using Rhodosporidium toruloides BCRC 21888 and Serratia marcescens BCRC10948 as biocatalysts
作者: 周曉怡
Chou, Hsiao-Yi
關鍵字: L-phenylephrine
沙雷氏黏質菌
Serratia marcescens
bioconversion
ketone reductase
生物轉換
酮基還原酶
出版社: 分子生物學研究所
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摘要: L-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.
L-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。
URI: http://hdl.handle.net/11455/22101
其他識別: U0005-1002201115135400
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-1002201115135400
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