固定化脂肪酶催化15-羟基十五烷酸甲酯合成环十五内酯的研究
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摘要
环十五内酯是一种具有珍贵麝香香气的大环麝香类化合物，广泛应用于香水、香精、化妆品、食品、医药等领域。目前对于该产品的合成受到国内外的青睐，特别是利用脂肪酶催化合成大环内酯的研究更是成为各国的研究热点。但对利用脂肪酶催化15—羟基十五烷酸甲酯合成环十五内酯研究并不充分，尤其是对其固定化脂肪酶催化特性及其在有机相中酸碱效应研究并未见有文献报道。本文即从这方面着手，开展了固定化脂肪酶催化15—羟基十五烷酸甲酯合成环十五内酯的研究。主要成果有如下几方面：
(1) 进行了脂肪酶的固定化，完成了其催化15—羟基十五烷酸甲酯合成环十五内酯研究。结果表明，固定化脂肪酶在反应过程中，对有机溶剂的稳定性及对水的耐受能力均比游离酶好，且经过多次重复使用后，固定化脂肪酶仍能保持良好的分散状态，且转化率有所上升，这一催化特性可以从诱导契合机制中得到解释。
(2) 探讨了脂肪酶催化15—羟基十五烷酸甲酯合成环十五内酯的溶剂效应。结果指出，环十五内酯的转化率与溶剂极性有关，所用溶剂极性越弱，环十五内酯的转化率越高。
(3) 考察了环化反应的酸碱效应。研究发现，环化效果与酶粉的pH记
Cyclopentadecanolide, which is a macrocyclic musk compound, is one of the best perfumes of musk. It is widely used in medicine, food, cosmetics, etc. Until now cyclopentadecanolide can mainly be yielded by chemical method. But the process of this method is so complicated, and the raw material costs so much that it can't be industrial. Since 15-Hydroxy-pentadecanoic acids were used as substrate to the synthesis of macrocyclic laction by lipase was discovered, the study on catalysis of macrocyclic lactone by lipase has been popular throughout the world. But catalysis of cyclopentadecanolide by lipase with Methyl 15-Hydroxy-pentadecanate has not been studied enough. Especially the catalytic characterizations of immobilized lipase and acid base effect have never been studied. So in this research, synthesis of cyclopentadecanolide with Methyl 15-Hydroxy-pentadecanate by immobilized lipase had been studied. The research contents include solvent effect, inductive effect, acid base effect, product inhibition and so on. The folio wings are the results:
(1) The immobilization of lipase had been studied in the research. And the immobilized lipase had been made to catalyze Methyl 15-Hydroxy-pentadecanate to become cyclopentadecanolide. Compared with free enzyme, immobilized lipase was much more stable in the organic solvent and had much stronger water proofness. Meanwhile, immobilized lipase still had good dispersivity and its catalytic activity went up rather than reduced after being repeated used. This catalytic characterization could be explained by induced-fit.
(2) Solvent effect of synthesis of cyclopentadecanolide by lipase used Methyl 15-Hydroxy-pentadecanate as substrate had been studied. The result showed that solvent polarity was bound up with conversion of cyclopentadecanolide. The conversion would go up if the solvent polarity were small. And cyclohexane was
(1) 进行了脂肪酶的固定化，完成了其催化15—羟基十五烷酸甲酯合成环十五内酯研究。结果表明，固定化脂肪酶在反应过程中，对有机溶剂的稳定性及对水的耐受能力均比游离酶好，且经过多次重复使用后，固定化脂肪酶仍能保持良好的分散状态，且转化率有所上升，这一催化特性可以从诱导契合机制中得到解释。
(2) 探讨了脂肪酶催化15—羟基十五烷酸甲酯合成环十五内酯的溶剂效应。结果指出，环十五内酯的转化率与溶剂极性有关，所用溶剂极性越弱，环十五内酯的转化率越高。
(3) 考察了环化反应的酸碱效应。研究发现，环化效果与酶粉的pH记
Cyclopentadecanolide, which is a macrocyclic musk compound, is one of the best perfumes of musk. It is widely used in medicine, food, cosmetics, etc. Until now cyclopentadecanolide can mainly be yielded by chemical method. But the process of this method is so complicated, and the raw material costs so much that it can't be industrial. Since 15-Hydroxy-pentadecanoic acids were used as substrate to the synthesis of macrocyclic laction by lipase was discovered, the study on catalysis of macrocyclic lactone by lipase has been popular throughout the world. But catalysis of cyclopentadecanolide by lipase with Methyl 15-Hydroxy-pentadecanate has not been studied enough. Especially the catalytic characterizations of immobilized lipase and acid base effect have never been studied. So in this research, synthesis of cyclopentadecanolide with Methyl 15-Hydroxy-pentadecanate by immobilized lipase had been studied. The research contents include solvent effect, inductive effect, acid base effect, product inhibition and so on. The folio wings are the results:
(1) The immobilization of lipase had been studied in the research. And the immobilized lipase had been made to catalyze Methyl 15-Hydroxy-pentadecanate to become cyclopentadecanolide. Compared with free enzyme, immobilized lipase was much more stable in the organic solvent and had much stronger water proofness. Meanwhile, immobilized lipase still had good dispersivity and its catalytic activity went up rather than reduced after being repeated used. This catalytic characterization could be explained by induced-fit.
(2) Solvent effect of synthesis of cyclopentadecanolide by lipase used Methyl 15-Hydroxy-pentadecanate as substrate had been studied. The result showed that solvent polarity was bound up with conversion of cyclopentadecanolide. The conversion would go up if the solvent polarity were small. And cyclohexane was
引文
[1] 李全，刘复初．麝香酮的合成进展[J]．合成化学，1998，6(1)：19—28
[2] 范成有．香料及其应用[M]，北京：化学工业出版社，1990：259
[3] 夏铮南，王文君．香料与香精[M]．北京：中国物资出版社，1998：315
[4] 何坚，孙保国．香料化学与工艺学[M]．北京：化学工业出版社，1999：561-563
[5] 唐健．内酯类麝香和二酯类麝香合成技术的发展[J]．北京日化，2002，66(1)： 26-29
[6] 张青山，霍怀民．巨环麝香十五碳内酯的合成综述[J]．华北工学院学报，1995，16(4)：339-344
[7] 孙建梅，陆洪芳，南家莲．利用蓖麻油发展精细化学品[J]．天津化工，2002，(7)： 19-21
[8] 姚素南，杨志国，佘志刚．以菜油为原料合成大环麝香化合物[J]．南昌大学学报，1994，16(2)：77-81
[9] 刘雄民，李伟光，李飘英．一种从蒜头果油制取环十五内酯的方法．中国发明专利．ZLO1132701．4，20020522
[10] Klibanov A M. Ezymic catalysis in anhydrous organic solvents [J]. Science, 1984, 224:1249
[11] Zaks A, Klibanov A M. Enzymatic catalysis in organic media at 100℃ [J]. Science, 1984, 224: 1249-1253.
[12] Zaks A, Klibanov A M. Enzymatic-catalyzed processes in organic solvents [J]. Proc Natl Acad Soc USA, 1985, 82: 3192-3196
[13] Altreuter D H., Dordick J S, Clark D S. Optimization of ion-paired lipase for non-aqueous media: acylation of doxorrubicin based on surface models of fatty acid esterification[J]. Enzyme and Micro Technol, 2002, 31:10-19
[14] Makita A, Nihira T, Yamada Y. Lipase catalyzed synthesis of macrocyclic lactones in organic solvents [J]. Tetrahedron Lett, 1987, 28(7): 805-808
[15] Kodera Y, Furukawa M., Yokoi M, et al. Lactone synthesis from 16-hydroxyhexadecanoic acid ethyl ester in organic solvents catalysed with polyethylene glycol-modified lipase [J]. Biotechnol, 1993, 31: 219-224
[16] Rees G D, Robinson B H, Stephenson G R. Macrocyclic lactone synthesis by lipases in water-in-oil microemulsions[J]. Biochem Biophys Acta, 1995, 1257: 239-248
[17] Miller C, Austin H, Posorske L. JAOCS [J], 1988, 65(6): 927-932
[18] Langrand G, Rondot N, Traiantap Hylides C. Short chain flavour esters synthesis by microbiol lipases [J]. Biotechnology Letters, 1990, 12(8): 581-586
[19] Shieh C J, Casimir C Akoh, Lisa N Yee. Optimized enzymatic synthesis of geranyl butyrate with lipase AY from Candida rugosa [J]. Biotechnology and Bioengineering, 1996, 51(2):371-374
[20] Gandolfi R, Converti A, Pirozzi D. Efficient and selective microbial esterification with dry mycelium ofRhizopus oryzae [J]. Biotechnol, 2001, 92(1): 6-21
[21] Mori K, Tom ioka H, Liebigs Ann. The role of venturis in pulse jet filters [J].Chem, 1992, 10:11
[22] Chen C, Chen Q. Biochemical study of chinese rhubarb.ⅪⅩ.localization of inhibition of anthraquinone derivatives on the mitochondrial respiratony chain [J]. Yaoxue Xuebao, 1987, 22(1): 12-18
[23] 潘冰峰，徐金旺，李祖义．脂肪酶催化合成内酯化合物的研究[J]．物化学与生物物理学，1998，30(4)：339-342
[24] 汪秋安，吴淑青．脂酶催化及其在香料合成中的应用[J]．香料香精化妆品，1999，12(4)：31-35
[25] Chibata I. Immobilized Enzyme [M]. Torornto: John Wiloy and Sons, 1978.
[26] 陈陶声，居乃琥，陈石根．固定化酶理论应用[M]．北京：北京轻工业出版社， 1987：196-200
[27] 杨玉玲．酶固定化技术及载体材料研究新进展[J]．粮油食品科技， 2001，9(5)：22-25
[28] [日]千烟一郎著，胡宝华译．固定化酶[M]．石家庄：河北人民出版社．1981：87
[29] 汤亚杰，吴思方，程婉农．壳聚糖固定化胰蛋白酶的研究[J]．食品科学，1991(1)： 29-32．
[30] 徐凤彩，李雪萍．壳聚糖固定化木瓜蛋白酶的研究[J]．生物化学杂志，1992，8(5)：608-613
[31] 魏远安，马丽，杨海等．固定化酶法合成蔗糖低聚糖的研究[J]．食品与发酵工业，1996(4)：12-16．
[32] Kennedy J F, et al. Immobilized living cells and their applications [J]. Appl Biochem. Bioeng, 1983, 38: 261-269
[33] 董海宝．生物化工[M]．北京：化学工业出版社，2001：287-296
[34] Quinn Z, Zhou K, Chen Xiao Dong. Immobilization of β-galactosidase on graphite surface by glutaraldehyde[J]. Food Eng, 2001, 48 (1): 69-74
[35] 赵裕卿．固定化酶应用[M]．应用微生物， 1988， (4)： 1
[36] Mitz MA, Summaria LJ. Nature [J], 1961, 189: 576
[37] Kozhukharova A, et al. Properties of Glucose Oxidase Immobilizedin Gel of Polyvinylalcohol [J]. Biotechnology and Bioengineering, 1988, 32 (2): 245-248
[38] Senay A C, Nurserin H, Oztop. Immobilization of catalase into chemically crossliked chitosan beads [J]. Enzyme and Microbial Technology, 2003, 32: 889-8 94
[39] 汪劲．环境与资源法学[M]．北京：高等教育出版社，2000：98-100
[40] [美]斯塔尼尔R Y．微生物世界[M]．北京：科学出版社，1983
[41] 周群英．环境工程微生物学[M]．北京：高等教育出版社，2000：256-258
[42] 马建标．高分子对酶、抗体、DNA的修饰、固定化及其生物医学应用[J]．高等学校化学学报，1997，18(7)：1227～1235
[43] Coulet P R, Immbilized enzymes on collagen membranes biotechnological perspectives [J]. Biochem Biophys Acta, 1980, 612: 317～327
[44] Hyman E D, Anal. Statistical modeling of passive-scalar diffusion in turbulent shear flows [J]. Biochem, 1988, 174(2): 423～436
[45] Makita A, Nihira T, Yamada Y. Lipase catalyzed synthesis of macrocylic lactiones in organic solvents [J]. Tetrahedron lett, 1987, 28(7): 805
[46] Yamane T, Kojima Y, Ichiryu T, et al. manufacture of ultrafine magnetic metal powder [J]. Biotechnology and Bioengineering, 1989, 34:838
[47] 潘湘波，梁静娟，刘雄民等．15-羟基十五烷酸的脂肪酶催化合成环十五内酯[J]．应用化学， 2004，21(8)：850—852
[48] Ke T, Klibanov A M. Markedly enhancing enzymatic enantioselectivity in organic solvents by forming substrate salts [J]. J Am Chem Soc, 1999, 121(14): 3334
[49] Harper N, Moore B D, Hailing P G. Tridodecylamine and its hydroehloride salt: an organic-soluble buffer for subtilisn Carlsberg in non-polar organic solvent [J]. Tetrahedron Lett, 2000, 41(21):4223.
[50] 周永红，李伟光，易封萍．气相色谱—质谱法测定蒜头果油中的脂肪酸[J]．色谱，2001，19(2)：147-148
[51] Luigi D M, Cynthia E , Gianpiero G Penicillin gamidase in low-water meida: immobilization and control of water activity by means of Celite rods[J]. Jmol Catalys B: Enzymatic, 1999, 6:437
[52] 潘冰峰，李祖义．应用生物法合成内酯化合物[J]．生物工程进展，1999，19(2)：52-55
[53] Tsuneo Yamane, Yoshikazu Kojima, Takayuki lchiry. Intramolecular Esterification by Lipase Powder in Microaqueous Benzene: Effect of Moisture Content u[J]. Biotechnology and Bioengineering, 1989, 34: 838-843
[54] 沈芳．长链脂肪酸酯的酶催化合成环十五内酯的研究[D]．南宁：广西大学，2005： 21-24
[55] Fischer E, Ber. Detsch. Chem. Ges[J], 1894, 27:2985
[56] Koshland Jr D E. Application of a theory of enzyme specificity to protain synthesis [J]. Proc Natl Acad Sci USA, 1958, 44:98
[57] 高修功，曹淑桂，章克昌．脂肪酶活性和选择性受溶剂不同物化参数控制[J]．ACTA BIOCHIMICA et BIOPHYSICA SINICA，1997，29(4)：337-342
[58] Klibanov A M. Trends Biochem Sci [J], 1989, 14:1141-145
[59] Mestri S D, Pai J S. Effect of moistrure on lipase-catalyzed esterfication of geraniol of palmarosa oil in non-aqueous system [J].Biotechbol Lett, 1995, 17:459-461
[60] Zaks A, Klibanov A M. Enzymatic catalysis in nonaquous solvent [J]. Biol Chem, 1988, 263:3194-3201
[61] Affleck R, Xu Z F, Suzawa V, et al. Enzymatic catalysis and dgnamics in Lower water environment [J]. Proc Natl Acad Sci USA, 1992, 89:1100-1104
[62] Chulalaksananukul W, Condoret J S. Geranyl acetate synthesis by lipase-catalyzed transesterfication in supercritical carbon dioxide [J]. Enzyme Microb Technol, 1993, 17:691-698
[63] 王丹，宋少芳，刘爱荣等．油包水微乳介质中脂肪酶催化-单硬脂酸甘油酯水解反应活性研究[J]．山东大学学报(理学版)．2002，37(6)：527-531
[64] 郭勇．酶的生产与应用[M]．北京：化学工业出版社，2003：169
[65] 叶蕴华，谢海波，田桂玲．非水溶剂中酶反应研究进展[J]．化学通报，1994(10)：5-9
[66] Rupley J A, Gratton E. Enzyme-collagen reactor designed from a hemodialysis module [J].Trends Biochem Sci, 1988, 8:18
[67] Careri G, Giansanti A. Biopolymer [J], 1979, 18:1187
[68] 周晓云．酶学原理与酶工程[M]．北京：中国轻工业出版社，2005：94-95
[69] 潘湘波．大环内酯化脂肪酶筛选及其酶法合成环十五内酯的研究[D]．南宁：广西大学，2004：23-24
[70] 郭杰炎，蔡武城．微生物酶[M]．北京：科学出版社，1986：165-168
[71] 朱洪法．催化剂载体[M]．北京：化学工业出版社，1980：43
[72] 徐如人，庞文琴．分子筛和多孔材料化学[M]．北京：科学出版社，2004：150
[73] 朗道，栗弗席兹著，周奇译．连续媒质电动力学[M]上册．北京：人民教育出版社．1956：66-67
[74] 姚允斌，解涛，高英敏，物理化学手册[B]．上海科学技术出版社，1985：784-812
[2] 范成有．香料及其应用[M]，北京：化学工业出版社，1990：259
[3] 夏铮南，王文君．香料与香精[M]．北京：中国物资出版社，1998：315
[4] 何坚，孙保国．香料化学与工艺学[M]．北京：化学工业出版社，1999：561-563
[5] 唐健．内酯类麝香和二酯类麝香合成技术的发展[J]．北京日化，2002，66(1)： 26-29
[6] 张青山，霍怀民．巨环麝香十五碳内酯的合成综述[J]．华北工学院学报，1995，16(4)：339-344
[7] 孙建梅，陆洪芳，南家莲．利用蓖麻油发展精细化学品[J]．天津化工，2002，(7)： 19-21
[8] 姚素南，杨志国，佘志刚．以菜油为原料合成大环麝香化合物[J]．南昌大学学报，1994，16(2)：77-81
[9] 刘雄民，李伟光，李飘英．一种从蒜头果油制取环十五内酯的方法．中国发明专利．ZLO1132701．4，20020522
[10] Klibanov A M. Ezymic catalysis in anhydrous organic solvents [J]. Science, 1984, 224:1249
[11] Zaks A, Klibanov A M. Enzymatic catalysis in organic media at 100℃ [J]. Science, 1984, 224: 1249-1253.
[12] Zaks A, Klibanov A M. Enzymatic-catalyzed processes in organic solvents [J]. Proc Natl Acad Soc USA, 1985, 82: 3192-3196
[13] Altreuter D H., Dordick J S, Clark D S. Optimization of ion-paired lipase for non-aqueous media: acylation of doxorrubicin based on surface models of fatty acid esterification[J]. Enzyme and Micro Technol, 2002, 31:10-19
[14] Makita A, Nihira T, Yamada Y. Lipase catalyzed synthesis of macrocyclic lactones in organic solvents [J]. Tetrahedron Lett, 1987, 28(7): 805-808
[15] Kodera Y, Furukawa M., Yokoi M, et al. Lactone synthesis from 16-hydroxyhexadecanoic acid ethyl ester in organic solvents catalysed with polyethylene glycol-modified lipase [J]. Biotechnol, 1993, 31: 219-224
[16] Rees G D, Robinson B H, Stephenson G R. Macrocyclic lactone synthesis by lipases in water-in-oil microemulsions[J]. Biochem Biophys Acta, 1995, 1257: 239-248
[17] Miller C, Austin H, Posorske L. JAOCS [J], 1988, 65(6): 927-932
[18] Langrand G, Rondot N, Traiantap Hylides C. Short chain flavour esters synthesis by microbiol lipases [J]. Biotechnology Letters, 1990, 12(8): 581-586
[19] Shieh C J, Casimir C Akoh, Lisa N Yee. Optimized enzymatic synthesis of geranyl butyrate with lipase AY from Candida rugosa [J]. Biotechnology and Bioengineering, 1996, 51(2):371-374
[20] Gandolfi R, Converti A, Pirozzi D. Efficient and selective microbial esterification with dry mycelium ofRhizopus oryzae [J]. Biotechnol, 2001, 92(1): 6-21
[21] Mori K, Tom ioka H, Liebigs Ann. The role of venturis in pulse jet filters [J].Chem, 1992, 10:11
[22] Chen C, Chen Q. Biochemical study of chinese rhubarb.ⅪⅩ.localization of inhibition of anthraquinone derivatives on the mitochondrial respiratony chain [J]. Yaoxue Xuebao, 1987, 22(1): 12-18
[23] 潘冰峰，徐金旺，李祖义．脂肪酶催化合成内酯化合物的研究[J]．物化学与生物物理学，1998，30(4)：339-342
[24] 汪秋安，吴淑青．脂酶催化及其在香料合成中的应用[J]．香料香精化妆品，1999，12(4)：31-35
[25] Chibata I. Immobilized Enzyme [M]. Torornto: John Wiloy and Sons, 1978.
[26] 陈陶声，居乃琥，陈石根．固定化酶理论应用[M]．北京：北京轻工业出版社， 1987：196-200
[27] 杨玉玲．酶固定化技术及载体材料研究新进展[J]．粮油食品科技， 2001，9(5)：22-25
[28] [日]千烟一郎著，胡宝华译．固定化酶[M]．石家庄：河北人民出版社．1981：87
[29] 汤亚杰，吴思方，程婉农．壳聚糖固定化胰蛋白酶的研究[J]．食品科学，1991(1)： 29-32．
[30] 徐凤彩，李雪萍．壳聚糖固定化木瓜蛋白酶的研究[J]．生物化学杂志，1992，8(5)：608-613
[31] 魏远安，马丽，杨海等．固定化酶法合成蔗糖低聚糖的研究[J]．食品与发酵工业，1996(4)：12-16．
[32] Kennedy J F, et al. Immobilized living cells and their applications [J]. Appl Biochem. Bioeng, 1983, 38: 261-269
[33] 董海宝．生物化工[M]．北京：化学工业出版社，2001：287-296
[34] Quinn Z, Zhou K, Chen Xiao Dong. Immobilization of β-galactosidase on graphite surface by glutaraldehyde[J]. Food Eng, 2001, 48 (1): 69-74
[35] 赵裕卿．固定化酶应用[M]．应用微生物， 1988， (4)： 1
[36] Mitz MA, Summaria LJ. Nature [J], 1961, 189: 576
[37] Kozhukharova A, et al. Properties of Glucose Oxidase Immobilizedin Gel of Polyvinylalcohol [J]. Biotechnology and Bioengineering, 1988, 32 (2): 245-248
[38] Senay A C, Nurserin H, Oztop. Immobilization of catalase into chemically crossliked chitosan beads [J]. Enzyme and Microbial Technology, 2003, 32: 889-8 94
[39] 汪劲．环境与资源法学[M]．北京：高等教育出版社，2000：98-100
[40] [美]斯塔尼尔R Y．微生物世界[M]．北京：科学出版社，1983
[41] 周群英．环境工程微生物学[M]．北京：高等教育出版社，2000：256-258
[42] 马建标．高分子对酶、抗体、DNA的修饰、固定化及其生物医学应用[J]．高等学校化学学报，1997，18(7)：1227～1235
[43] Coulet P R, Immbilized enzymes on collagen membranes biotechnological perspectives [J]. Biochem Biophys Acta, 1980, 612: 317～327
[44] Hyman E D, Anal. Statistical modeling of passive-scalar diffusion in turbulent shear flows [J]. Biochem, 1988, 174(2): 423～436
[45] Makita A, Nihira T, Yamada Y. Lipase catalyzed synthesis of macrocylic lactiones in organic solvents [J]. Tetrahedron lett, 1987, 28(7): 805
[46] Yamane T, Kojima Y, Ichiryu T, et al. manufacture of ultrafine magnetic metal powder [J]. Biotechnology and Bioengineering, 1989, 34:838
[47] 潘湘波，梁静娟，刘雄民等．15-羟基十五烷酸的脂肪酶催化合成环十五内酯[J]．应用化学， 2004，21(8)：850—852
[48] Ke T, Klibanov A M. Markedly enhancing enzymatic enantioselectivity in organic solvents by forming substrate salts [J]. J Am Chem Soc, 1999, 121(14): 3334
[49] Harper N, Moore B D, Hailing P G. Tridodecylamine and its hydroehloride salt: an organic-soluble buffer for subtilisn Carlsberg in non-polar organic solvent [J]. Tetrahedron Lett, 2000, 41(21):4223.
[50] 周永红，李伟光，易封萍．气相色谱—质谱法测定蒜头果油中的脂肪酸[J]．色谱，2001，19(2)：147-148
[51] Luigi D M, Cynthia E , Gianpiero G Penicillin gamidase in low-water meida: immobilization and control of water activity by means of Celite rods[J]. Jmol Catalys B: Enzymatic, 1999, 6:437
[52] 潘冰峰，李祖义．应用生物法合成内酯化合物[J]．生物工程进展，1999，19(2)：52-55
[53] Tsuneo Yamane, Yoshikazu Kojima, Takayuki lchiry. Intramolecular Esterification by Lipase Powder in Microaqueous Benzene: Effect of Moisture Content u[J]. Biotechnology and Bioengineering, 1989, 34: 838-843
[54] 沈芳．长链脂肪酸酯的酶催化合成环十五内酯的研究[D]．南宁：广西大学，2005： 21-24
[55] Fischer E, Ber. Detsch. Chem. Ges[J], 1894, 27:2985
[56] Koshland Jr D E. Application of a theory of enzyme specificity to protain synthesis [J]. Proc Natl Acad Sci USA, 1958, 44:98
[57] 高修功，曹淑桂，章克昌．脂肪酶活性和选择性受溶剂不同物化参数控制[J]．ACTA BIOCHIMICA et BIOPHYSICA SINICA，1997，29(4)：337-342
[58] Klibanov A M. Trends Biochem Sci [J], 1989, 14:1141-145
[59] Mestri S D, Pai J S. Effect of moistrure on lipase-catalyzed esterfication of geraniol of palmarosa oil in non-aqueous system [J].Biotechbol Lett, 1995, 17:459-461
[60] Zaks A, Klibanov A M. Enzymatic catalysis in nonaquous solvent [J]. Biol Chem, 1988, 263:3194-3201
[61] Affleck R, Xu Z F, Suzawa V, et al. Enzymatic catalysis and dgnamics in Lower water environment [J]. Proc Natl Acad Sci USA, 1992, 89:1100-1104
[62] Chulalaksananukul W, Condoret J S. Geranyl acetate synthesis by lipase-catalyzed transesterfication in supercritical carbon dioxide [J]. Enzyme Microb Technol, 1993, 17:691-698
[63] 王丹，宋少芳，刘爱荣等．油包水微乳介质中脂肪酶催化-单硬脂酸甘油酯水解反应活性研究[J]．山东大学学报(理学版)．2002，37(6)：527-531
[64] 郭勇．酶的生产与应用[M]．北京：化学工业出版社，2003：169
[65] 叶蕴华，谢海波，田桂玲．非水溶剂中酶反应研究进展[J]．化学通报，1994(10)：5-9
[66] Rupley J A, Gratton E. Enzyme-collagen reactor designed from a hemodialysis module [J].Trends Biochem Sci, 1988, 8:18
[67] Careri G, Giansanti A. Biopolymer [J], 1979, 18:1187
[68] 周晓云．酶学原理与酶工程[M]．北京：中国轻工业出版社，2005：94-95
[69] 潘湘波．大环内酯化脂肪酶筛选及其酶法合成环十五内酯的研究[D]．南宁：广西大学，2004：23-24
[70] 郭杰炎，蔡武城．微生物酶[M]．北京：科学出版社，1986：165-168
[71] 朱洪法．催化剂载体[M]．北京：化学工业出版社，1980：43
[72] 徐如人，庞文琴．分子筛和多孔材料化学[M]．北京：科学出版社，2004：150
[73] 朗道，栗弗席兹著，周奇译．连续媒质电动力学[M]上册．北京：人民教育出版社．1956：66-67
[74] 姚允斌，解涛，高英敏，物理化学手册[B]．上海科学技术出版社，1985：784-812