拟指数流加补料高密度培养重组E.coli产甲酸脱氢酶
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摘要
甲酸脱氢酶(Formate dedydrogenase,FDH)被认为是催化辅酶NADH高效再生的最佳酶选,绝大多数FDH是NAD_-~+依赖型,能专一性地把甲酸根氧化成CO_2和H~+,同时催化NAD~+还原得到NADH。FDH构建的辅酶NADH再生体系,可与醇脱氢酶(Alcoholdedydrogenase,ADH)耦联,催化前手性酮不对称还原制备高价值的手性醇、手性氨基酸、手性羟基酸/酯等。利用重组大肠杆菌可以高效率表达FDH基因,但副产物乙酸的积累会影响细胞内FDH的积累,这一直是FDH生产一个亟待解决的问题。
本工作的目的是建立拟指数流加补料高密度培养FDH重组大肠杆菌培养的发酵工艺,以副产物乙酸为关键控制点,优化工艺和补料策略,尽可能避免葡萄糖效应,减轻乙酸的抑制作用,提高FDH产量,缩短发酵周期,降低能源设备成本。并拟进一步研究FDH催化辅酶NADH体系的应用,将其与红串红球菌ADH组建耦联反应体系,催化4-氯乙酰乙酸乙酯(COBE)不对称还原生成(R)-4-氯-3-羟基-丁酸乙酯((R)-CHBE),验证FDH催化辅酶NADH体系的应用可行性和效率。
本文首先建立并验证了分阶段匀速流加补料模拟指数流加的方法,确定重组菌E.coliBL21(DE3)/pET 28a(+)-fdh的表观得率系数Y_(X/S)。在此基础上,重点研究了15 L发酵罐上FDH重组菌的拟指数流加补料高密度培养工艺。优化诱导时机、诱导前的补料策略和诱导后的比生长速率控制,以降低乙酸积累和提高FDH产量为主要调控指标。最终建立了批次发酵、诱导前流加补料和诱导后流加补料三阶段的培养模式,批次发酵结束后,采用比生长速率为0.05 h~(-1)的拟指数流加补料策略,待生物量达到11.0 g DCW/L(OD_(600) 25)后加入终浓度为0.4 mM的IPTG诱导,培养温度降为28℃。诱导后的比生长速率控制在0.08 h~(-1)。pH控制在7.0。最终生物量为41.20 g DCW/L(OD_(600) 114.8),FDH产量为26.24×10~3U/L,单位细胞干重FDH活力为636.9 U/g DCW。FDH的产量比批次发酵、诱导-补料(pH-stat法)两阶段法高密度培养提高了1.17倍,且大大缩短了发酵周期,节约成本。
构建红串红球菌Rhodococcus erythropolis ATCC 17896的ADH重组菌E.coliBL21(DE3)/pET 28a(+)-adh,并优化了重组菌的诱导表达条件。组建ADH-FDH粗酶液耦联体系,催化COBE的不对称还原,(R)-CHBE的时空产率为7.125 mol/(L·h),对映体过量率(e.e.)值89(±1.4)%,NADH的周转率为150 mol/mol。证明FDH催化甲酸钠再生NADH的体系是可行的,效率较高。
Formate dehydrogenase(FDH) is known as one of the most promising catalyst for in situ regeneration ofβ-nicotinamide adenine dinucleotide(NADH).FDHs are mainly NAD~+-dependent in aerobic organisms,which catalyze oxidation of formate to carbon dioxide with commitment reduction of NAD~+ to NADH.NADH regeneration using FDH can be widely applied in asymmetric reduction of prochiral carbonyl compounds with alcohol dehydrogenases (ADH),a promising route for synthesis of valuable optically active alcohols,amino acids, hydroxyl acids or esters.However,large-scale production of FDH is still a tough task at present, because acetate overflow in aerobically grown cultures of E.coli is a major problem in high cell density cultivation for large-scale production of FDH.
The objective of this work is to develop an efficient high cell density cultivation process with pseudo-exponential fed-batch strategy,focused on reducing the formation of acetate and overflow metabolism by optimizing the fed-batch strategy,and finally grew recombinant E.coli to high cell densities for enhanced production of FDH intracellularly,saving time and energy cost.The efficiency of in situ NADH regeneration by FDH was evaluated by reducing 4-Chloro acetoacetate ethyl(COBE) to(R)-4-chloro-3-hydroxy ethyl butyrate(CHBE) when FDH is coupled with ADH from Rhodococcus erythropolis ATCC 17896.
Firstly,the glucose feeding rate was stepwisely changed every 2 hours to simulate the exponential feeding strategy,controlling the specific growth rate at the predetermined set point ofμ_(set).Then the apparent yield coefficient Y_(X/S) was investigated and set at 0.3 g DCW/g glucose cultivating E.coli BL21(DE3)/pET 28a(+)-fdh.Based on the preliminary results,induction time and fed-batch strategy in the pre-induction stage were optimized for fermentation of recombinant E.coli in completely defined medium.And pseudo-exponential feeding strategy under three different specific growth rates in post-induction stage was further investigated to reduce acetate accumulation,prolong the FDH production period,and most importantly to maximize FDH production and intracellular FDH activity.This three-step cultivation was operated as follows: Pseudo-exponential fed-batch fermentation controlled at specific growth rate of 0.05 h~(-1) was employed in pre-induction stage after batch fermentation.Until the biomass reached 11.0 g DCW/L(with OD_(600) around 25),induction was carded out by adding 0.4 mM IPTG and the temperature was reduced to 28℃.The specific growth rate in the subsequent post-induction stage was set at 0.08 h~(-1).pH was maintained at 7.0 during the whole fermentation.The biomass attained was 41.20 g DCW/L(OD_(600) 114.8).The maximum FDH production and intracellular FDH activity,was 26.24×10~3 U/L and 636.9 U/g DCW,respectively.The FDH production abtained in this three-step way was enhanced by 1.17 times than the earlier result got from two-step cultivation with batch and pH-stat fed-batch.The results showed that low set-value of specific growth rate led to lower glucose feeding rate and less overflow metabolism,thus delayed the formation of acetate,and finally increased the FDH production significantly.And it also helps to save time and energer greatly.
Recombinant E.coli BL21(DE3)/pET 28a(+)-adh was constructed with ADH gene from Rhodococcus erythropolis ATCC 17896,and the ADH expression condition was optimized.Then COBE was reduced to produce(R)-CHBE by ADH coupled with in situ NADH regeneration catalyzed by FDH.15 mM COBE was reduced completely in less than 2 hours.And the productivity of(R)-CHBE was 7.125 mol/(L·h),the enantio excess was 89(±1.4)%,with the total turnover number(TTN) at 150 mol/mol.The successful application proved FDH produced in our lab was capable and applicable in efficient NADH regeneration.FDH is a promising NADH regenerator for synthesis of high value products.
本工作的目的是建立拟指数流加补料高密度培养FDH重组大肠杆菌培养的发酵工艺,以副产物乙酸为关键控制点,优化工艺和补料策略,尽可能避免葡萄糖效应,减轻乙酸的抑制作用,提高FDH产量,缩短发酵周期,降低能源设备成本。并拟进一步研究FDH催化辅酶NADH体系的应用,将其与红串红球菌ADH组建耦联反应体系,催化4-氯乙酰乙酸乙酯(COBE)不对称还原生成(R)-4-氯-3-羟基-丁酸乙酯((R)-CHBE),验证FDH催化辅酶NADH体系的应用可行性和效率。
本文首先建立并验证了分阶段匀速流加补料模拟指数流加的方法,确定重组菌E.coliBL21(DE3)/pET 28a(+)-fdh的表观得率系数Y_(X/S)。在此基础上,重点研究了15 L发酵罐上FDH重组菌的拟指数流加补料高密度培养工艺。优化诱导时机、诱导前的补料策略和诱导后的比生长速率控制,以降低乙酸积累和提高FDH产量为主要调控指标。最终建立了批次发酵、诱导前流加补料和诱导后流加补料三阶段的培养模式,批次发酵结束后,采用比生长速率为0.05 h~(-1)的拟指数流加补料策略,待生物量达到11.0 g DCW/L(OD_(600) 25)后加入终浓度为0.4 mM的IPTG诱导,培养温度降为28℃。诱导后的比生长速率控制在0.08 h~(-1)。pH控制在7.0。最终生物量为41.20 g DCW/L(OD_(600) 114.8),FDH产量为26.24×10~3U/L,单位细胞干重FDH活力为636.9 U/g DCW。FDH的产量比批次发酵、诱导-补料(pH-stat法)两阶段法高密度培养提高了1.17倍,且大大缩短了发酵周期,节约成本。
构建红串红球菌Rhodococcus erythropolis ATCC 17896的ADH重组菌E.coliBL21(DE3)/pET 28a(+)-adh,并优化了重组菌的诱导表达条件。组建ADH-FDH粗酶液耦联体系,催化COBE的不对称还原,(R)-CHBE的时空产率为7.125 mol/(L·h),对映体过量率(e.e.)值89(±1.4)%,NADH的周转率为150 mol/mol。证明FDH催化甲酸钠再生NADH的体系是可行的,效率较高。
Formate dehydrogenase(FDH) is known as one of the most promising catalyst for in situ regeneration ofβ-nicotinamide adenine dinucleotide(NADH).FDHs are mainly NAD~+-dependent in aerobic organisms,which catalyze oxidation of formate to carbon dioxide with commitment reduction of NAD~+ to NADH.NADH regeneration using FDH can be widely applied in asymmetric reduction of prochiral carbonyl compounds with alcohol dehydrogenases (ADH),a promising route for synthesis of valuable optically active alcohols,amino acids, hydroxyl acids or esters.However,large-scale production of FDH is still a tough task at present, because acetate overflow in aerobically grown cultures of E.coli is a major problem in high cell density cultivation for large-scale production of FDH.
The objective of this work is to develop an efficient high cell density cultivation process with pseudo-exponential fed-batch strategy,focused on reducing the formation of acetate and overflow metabolism by optimizing the fed-batch strategy,and finally grew recombinant E.coli to high cell densities for enhanced production of FDH intracellularly,saving time and energy cost.The efficiency of in situ NADH regeneration by FDH was evaluated by reducing 4-Chloro acetoacetate ethyl(COBE) to(R)-4-chloro-3-hydroxy ethyl butyrate(CHBE) when FDH is coupled with ADH from Rhodococcus erythropolis ATCC 17896.
Firstly,the glucose feeding rate was stepwisely changed every 2 hours to simulate the exponential feeding strategy,controlling the specific growth rate at the predetermined set point ofμ_(set).Then the apparent yield coefficient Y_(X/S) was investigated and set at 0.3 g DCW/g glucose cultivating E.coli BL21(DE3)/pET 28a(+)-fdh.Based on the preliminary results,induction time and fed-batch strategy in the pre-induction stage were optimized for fermentation of recombinant E.coli in completely defined medium.And pseudo-exponential feeding strategy under three different specific growth rates in post-induction stage was further investigated to reduce acetate accumulation,prolong the FDH production period,and most importantly to maximize FDH production and intracellular FDH activity.This three-step cultivation was operated as follows: Pseudo-exponential fed-batch fermentation controlled at specific growth rate of 0.05 h~(-1) was employed in pre-induction stage after batch fermentation.Until the biomass reached 11.0 g DCW/L(with OD_(600) around 25),induction was carded out by adding 0.4 mM IPTG and the temperature was reduced to 28℃.The specific growth rate in the subsequent post-induction stage was set at 0.08 h~(-1).pH was maintained at 7.0 during the whole fermentation.The biomass attained was 41.20 g DCW/L(OD_(600) 114.8).The maximum FDH production and intracellular FDH activity,was 26.24×10~3 U/L and 636.9 U/g DCW,respectively.The FDH production abtained in this three-step way was enhanced by 1.17 times than the earlier result got from two-step cultivation with batch and pH-stat fed-batch.The results showed that low set-value of specific growth rate led to lower glucose feeding rate and less overflow metabolism,thus delayed the formation of acetate,and finally increased the FDH production significantly.And it also helps to save time and energer greatly.
Recombinant E.coli BL21(DE3)/pET 28a(+)-adh was constructed with ADH gene from Rhodococcus erythropolis ATCC 17896,and the ADH expression condition was optimized.Then COBE was reduced to produce(R)-CHBE by ADH coupled with in situ NADH regeneration catalyzed by FDH.15 mM COBE was reduced completely in less than 2 hours.And the productivity of(R)-CHBE was 7.125 mol/(L·h),the enantio excess was 89(±1.4)%,with the total turnover number(TTN) at 150 mol/mol.The successful application proved FDH produced in our lab was capable and applicable in efficient NADH regeneration.FDH is a promising NADH regenerator for synthesis of high value products.
引文
[1] M. Jormakka, B. Byrne, S. Iwata. Formate dehydrogenase - a versatile enzyme in changing environments. Current Opinion in Structural Biology, 2003. 13(4) 418-423.
[2] V.I. Tishkov, V.O. Popov. Protein engineering of formate dehydrogenase. Biomolecular Engineering, 2006.23(2-3)89-110.
[3] V.I. Tishkov, A.G Galkin, V.V. Fedorchuk, et al. Pilot scale production and isolation of recombinant NAD+- and NADP+-specific formate dehydrogenases. Biotechnol Bioeng, 1999. 64(2) 187-193.
[4] V.V. Karzanov, Y.A. Bogatsky, V.I. Tishkov, et al. Evidence for the Presence of a New Nad+-Dependent Formate Dehydrogenase in Pseudomonas Sp-101 Cells Grown on a Molybdenum-Containing Medium. FEMS Microbiology Letters, 1989. 60(2) 197-200.
[5] V.I. Tishkov, V.O. Popov. Catalytic mechanism and application of formate dehydrogenase. Biochemistry (Mosc), 2004. 69(11) 1252-1267.
[6] A. Galkin, L. Kulakova, V. Tishkov, et al. Cloning of formate dehydrogenase gene from a methanol-utilizing bacterium Mycobacterium vaccae N10. Applied microbiology and biotechnology, 1995.44(3-4)479-483.
[7] T. Shinoda, T. Satoh, S. Mineki, et al. Cloning, Nucleotide Sequencing, and Expression in Escherichia coli of the Gene for Formate Dehydrogenase of Paracoccus sp. 12-A, a Formate-assimilating Bacterium. Bioscience, Biotechnology, and Biochemistry, 2002. 66(2) 271-276.
[8] H. Nanba, Y. Takaoka, J. Hasegawa. Purification and characterization of formate dehydrogenase from Ancylobacter aquaticus strain KNK607M, and cloning of the gene. Bioscience Biotechnology and Biochemistry, 2003. 67(4) 720-728.
[9] H. Nanba, Y. Takaoka, J. Hasegawa. Purification and characterization of an alpha-haloketone-resistant formate dehydrogenase from Thiobacillus sp strain KNK65MA, and cloning of the gene. Bioscience Biotechnology and Biochemistry, 2003. 67(10) 2145-2153.
[10] SJ. Allen, J.J. Holbrook. Isolation, sequence and overexpression of the gene encoding NAD-dependent formate dehydrogenase from the methylotrophic yeast Candida methylica. Gene, 1995. 162(1)99-104.
[11] H. Slusarczyk, S. Felber, M.R. Kula, et al. Stabilization of NAD-dependent formate dehydrogenase from Candida boidinii by site-directed mutagenesis of cysteine residues. European Journal of Biochemistry, 2000. 267(5) 1280-1289.
[12] J.E. Galagan, S.E. Calvo, C. Cuomo, et al. Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature, 2005. 438(7071) 1105-1115.
[13] J.E. Galagan, S.E. Calvo, K.A. Borkovich, et al. The genome sequence of the filamentous fungus Neurospora crassa. Nature, 2003. 422(6934) 859-868.
[14] K. Suzuki, R. Itai, K. Suzuki, et al. Formate Dehydrogenase, an Enzyme of Anaerobic Metabolism, Is Induced by Iron Deficiency in Barley Roots.PLANT PHYSIOLOGY,1998.116(2) 725-732.
[15]P.L.Herman,H.Ramberg,R.D.Baack,et al.Formate dehydrogenase in Arabidopsis thaliana:overexpression and subcellular localization in leaves.Plant Science,2002.163(6) 1137-1145.
[16]A.G.Galkin,A.S.Kutsenko,N.P.Bajulina,et al.Site-directed mutagenesis of the essential arginine of the formate dehydrogenase active centre.Biochimica Et Biophysica Acta-Protein Structure and Molecular Enzymoiogy,2002.1594(1) 136-149.
[17]V.O.Popov,V.S.Lamzin.Nad(+)-Dependent Formate Dehydrogenase.Biochemical Journal,1994.301 625-643.
[18]V.I.Tishkov,A.G.Galkin,A.M.Egorov.Kinetic isotope effect and the presteady-state kinetics of the reaction catalyzed by the bacterial formate dehydrogenase.Biochimie,1989.71(4) 551-557.
[19]A.E.Serov,A.S.Popova,V.V.Fedorchuk,et al.Engineering of coenzyme specificity of formate dehydrogenase from Saccharomyces cerevisiae.Biochemical Journal,2002.367 841-847.
[20]K.Seelbach,B.Riebel,W.Hummel,et al.A novel,efficient regenerating method of NADPH using a new formate dehydrogenase.Tetrahedron Letters,1996.37(9) 1377-1380.
[21]A.D.Ellington,J.J.Bull.Evolution.Changing the cofactor diet of an enzyme.Science,2005.310(5747) 454-5.
[22]N.Gul-Karaguler,R.B.Sessions,A.R.Clarke,et al.A single mutation in the NAD-specific formate dehydrogenase from Candida methylica allows the enzyme to use NADP.Biotechnology Letters,2001.23(4) 283-287.
[23]V.I.Tishkov,A.G.Galkin,O.A.Egorova,et al.Site-Directed Mutagenesis of Bacterial Formate Dehydrogenase - Role of Cys-255 in the Enzyme Catalysis and Stability.Doklady Akademii Nauk,1993.328(3) 407-410.
[24]A.M.Rojkova,A.G.Galkin,L.B.Kulakova,et al.Bacterial formate dehydrogenase.Increasing the enzyme thermal stability by hydrophobization of alpha-helices.Febs Letters,1999.445(1) 183-188.
[25]A.E.Serov,E.R.Odintzeva,I.V.Uporov,et al.Use of ramachandran plot for increasing thermal stability of bacterial formate dehydrogenase.Biochemistry-Moscow,2005.70(7) 804-808.
[26]A.V.Mesentsev,V.S.Lamzin,V.I.Tishkov,et al.Effect of pH on kinetic parameters of NAD(+)-dependent formate dehydrogenase.Biochemical Journal,1997.321 475-480.
[27]V.I.Tishkov,A.G.Galkin,A.M.Yegorov.Nad-Dependent Formate Dehydrogenase from Methylotrophic Bacterium Pseudomonas Sp 101 - Cloning,Expression and Study of Gene Structure.Doklady Akademii Nauk Sssr,1991.317(3) 745-748.
[28]S.Heike,F.Stefan,K.Maria-Regina,et al.Candida boidinii formic hydrogenase mutants.Germany.EP1295937(A2).20030326.
[29]R.Li,B.Ziola,J.King.Purification and characterization of formate dehydrogenase from Arabidopsis thaliana.Journal of Plant Physiology,2000.157(2) 161-167.
[30]R.DevauxBasseguy,A.Bergel,M.Comtat.Potential applications of NAD(P)-dependent oxidoreductases in synthesis:A survey.Enzyme and Microbial Technology,1997.20(4) 248-258.
[31]W.Hummel.New alcohol dehydrogenases for the synthesis of chiral compounds.Advances in biochemical engineering/biotechnology,1997.58 145-184.
[32]K.Goldberg,K.Schroer,S.Lutz,et al.Biocatalytic ketone reduction—a powerful tool for the production of chiral alcohols—part Ⅰ:processes with isolated enzymes.Applied microbiology and biotechnology,2007.76(2) 237-248.
[33]W.F.Liu,P.Wang.Cofactor regeneration for sustainable enzymatic biosynthesis.Biotechnology advances,2007.25(4) 369-384.
[34]W.Hummel,M.R.Kula.Dehydrogenases for the Synthesis of Chiral Compounds.European Journal of Biochemistry,1989.184(1)1-13.
[35]K.Nakamura,R.Yamanaka,T.Matsuda,et al.Recent developments in asymmetric reduction of ketones with biocatalysts.Tetrahedron-Asymmetry,2003.14(18) 2659-2681.
[36]P.S.Wagenknecht,J.M.Penney,R.T.Hembre.Transition-metal-catalyzed regeneration of nicotinamide coenzymes with hydrogen.Organometallics,2003.22(6) 1180-1182.
[37]R.Yuan,S.Watanabe,S.Kuwabata,et al.Asymmetric electroreduction of ketone and aldehyde derivatives to the corresponding alcohols using alcohol dehydrogenase as an electrocatalyst.Journal of Organic Chemistry,1997.62(8) 2494-2499.
[38]I.Willner,R.Maidan,M.Shapira.Thermal and Photochemical Regeneration of Nicotinamide Cofactors and a Nicotinamide Model-Compound Using a Water-Soluble Rhodium Phosphine Catalyst.Journal of the Chemical Society-Perkin Transactions 2,1990(4) 559-564.
[39]M.Julliard,J.Lepetit,P.Ritz.Regeneration of Nad+ Cofactor by Photosensitized Electron-Transfer in an Immobilized Alcohol-Dehydrogenase System.Biotechnology and Bioengineering,1986.28(12)1774-1779.
[40]Q.Shi,D.Yang,Z.Jiang,et al.Visible-light photocatalytic regeneration of NADH using P-doped TiO2 nanoparticles.Journal of Molecular Catalysis B:Enzymatic,2006.43(1-4) 44-48.
[41]Z.Findrik,D.Vasic-Racki,S.Lutz,et al.Kinetic modeling of acetophenone reduction catalyzed by alcohol.dehydrogenase from Thermoanaerobacter sp.Biotechnology Letters,2005.27(15)1087-1095.
[42]W.Kroutil,H.Mang,K.Edegger,et al.Recent advances in the biocatalytic reduction of ketones and oxidation of sec-alcohols.Current Opinion in Chemical Biology,2004.8(2) 120-126.
[43]S.Shimizu,M.Kataoka,M.Katoh,et al.Stereoselective Reduction of Ethyl 4-Chloro-3-Oxobutanoate by a Microbial Aldehyde Reductase in an Organic Solvent-Water Diphasic System.Applied and Environmental Microbiology,1990.56(8) 2374-2377.
[44]A.S.Bommarius,M.Schwarm,K.Stingl,et al.Synthesis and use of enantiomericaily pure tert-leucine.Tetrahedron:Asymmetry,1995.6(12) 2851-2888.
[45]R.Wichmann,C.Wandrey,A.F.Buckmann,et al.CONTINUOUS ENZYMATIC TRANSFORMATION IN AN ENZYME MEMBRANE REACTOR WITH SIMULTANEOUS NAD(H) REGENERATION.Biotechnology and Bioengineering,1981.23(12) 2789-2802.
[46]Y.L.Bai,S.T.Yang.Biotransformation of R-2-hydroxy-4-phenylbutyric acid by D-lactate dehydrogenase and Candida boidinii cells containing formate dehydrogenase coimmobilized in a fibrous bed bioreactor.Biotechnology and Bioengineering,2005.92(2) 137-146.
[47]M.Ernst,B.Kaup,M.Muller,et al.Enantioselective reduction of carbonyl compounds by whole-cell biotransformation,combining a formate dehydrogenase and a(R)-specific alcohol dehydrogenase.Applied microbiology and biotechnology,2005.66(6) 629-634.
[48]T.W.Johannes,R.D.Woodyer,H.M.Zhao.Efficient regeneration of NADPH using an engineered phosphite dehydrogenase.Biotechnology and Bioengineering,2007.96(1) 18-26.
[49]M.M.Musa,K.I.Ziegelmann-Fjeld,C.Vieile,et al.Asymmetric reduction and oxidation of aromatic ketones and alcohols using W110A secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus.Journal of Organic Chemistry,2007.72(1) 30-34.
[50]刘子宇,李平兰,郑海涛,等.微生物高密度培养的研究进展.中国乳业,2005(12)47-51.
[51]S.Y.Lee.High cell-density culture of Escherichia coli.Trends in Biotechnology,1996.14(3) 98-105.
[52]D.Riesenberg,R.Guthke.High-cell-density cultivation of microorganisms.Applied microbiology and biotechnology,1999.51(4) 422-430.
[53]李民,陈常庆.重组大肠杆菌高密度发酵研究进展.生物工程进展,2000.20(2)26-31.
[54]A.M.Sanden,I.Prytz,I.Tubulekas,et al.Limiting factors in Escherichia coli fed-batch production of recombinant proteins.Biotechnology and Bioengineering,2003.81(2) 158-66.
[55]P.Neubauer,H.Y.Lin,B.Mathiszik.Metabolic load of recombinant protein production:Inhibition of cellular capacities for glucose uptake and respiration after induction of a heteroiogous gene in Escherichia coli.Biotechnology and Bioengineering,2003.83(1) 53-64.
[56]A.M.Sanden,I.Prytz,I.Tubulekas,et al.Limiting factors in Escherichia coli fed-batch production of recombinant proteins.Biotechnology and Bioengineering,2003.81(2) 158-166.
[57]T.Suzuki.A dense cell culture system for microorganisms using a stirred ceramic membrane reactor incorporating asymmetric porous ceramic filters.Journal of Fermentation and Bioengineering,1996.82(3) 264-271.
[58]K.Nakano,M.Rischke,S.Sato,et al.Influence of acetic acid on the growth of Escherichia coli K12during high-cell-density cultivation in a dialysis reactor.Applied microbiology and biotechnology,1997.48(5) 597-601.
[59]J.Shiloach,R.Fass.Growing E-coli to high cell density - A historical perspective on method development.Biotechnology Advances,2005.23(5) 345-357.
[60]L.C.Cheng,J.Y.Wu,T.L.Chen.A pseudo-exponential feeding method for control of specific growth rate in fed-batch cultures.Biochemical Engineering Journal,2002.10(3) 227-232.
[61]S.S.Yazdani,A.R.Shakri,C.E.Chitnis.A high cell density fermentation strategy to produce recombinant malarial antigen in E-coli.Biotechnology Letters,2004.26(24) 1891-1895.
[62]B.Kim,S.Lee,S.Lee,et al.High cell density fed-batch cultivation of Escherichia coli using exponential feeding combined with pH-stat.Bioprocess and Biosystems Engineering,2004.26(3)147-150.
[63]R.Khalilzadeh,S.A.Shojaosadati,A.Bahrami,et al.Over-expression of recombinant human interferon-gamma in high cell density fermentation of Escherichia coli.Biotechnology Letters,2003. 25(23) 1989-1992.
[64]V.S.Whiffin,M.J.Cooney,R.Cord-Ruwisch.Online detection of feed demand in high cell density cultures of Escherichia coli by measurement of changes in dissolved oxygen transients in complex media.Biotechnology and Bioengineering,2004.85(4) 422-433.
[65]M.Akesson,P.Hagander,J.P.Axelsson.Avoiding acetate accumulation in Escherichia coli cultures using feedback control of glucose feeding,Biotechnology and Bioengineering,2001.73(3) 223-230.
[66]E.A.Sandoval-Basurto,G.Gosset,F.Bolivar,et al.Culture of Escherichia coli under dissolved oxygen gradients simulated in a two-compartment scale-down system:Metabolic response and production of recombinant protein.Biotechnology and Bioengineering,2005.89(4) 453-463.
[67]T.Matsui,N.Shinzato,H.Yokota,et al.High cell density cultivation of recombinant E-coli with a pressurized culture.Process Biochemistry,2006.41(4) 920-924.
[68]M.Akesson,E.N.Karisson,P.Hagander,et al.On-line detection of acetate formation in Escherichia coli cultures using dissolved oxygen responses to feed transients.Biotechnology and Bioengineering,1999.64(5) 590-598.
[69]U.Horn,W.Strittmarter,A.Krebber,et al.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.Applied microbiology and biotechnology,1996.46(5-6) 524-532.
[70]李民,陈常庆,朴勤,等.利用恒溶氧-补料分批技术高密度培养大肠杆菌生产重组人骨形成蛋白-2A.生物工程学报,1998.14(3)270-275.
[71]K.R.Babu,S.Swaminathan,S.Marten,et al.Production of interferon-α in high cell density cultures of recombinant Escherichia coli and its single step purification from refolded inclusion body proteins Applied microbiology and biotechnology,2000.53(6) 655-660.
[72]J.Qiu,J.R.Swartz,G.Georgiou.Expression of active human tissue-type plasminogen activator in Escherichia coli.Applied and Environmental Microbiology,1998.64(12) 4891-4896.
[73]J.Pinsach,C.de Mas,J.Lopez-Santin.A simple feedback control of Escherichia coli growth for recombinant aidolase production in fed-batch mode.Biochemical Engineering Journal,2006.29(3)235-242.
[74]O.Durany,C.de Mas,J.Lopez-Santin.Fed-batch production of recombinant fuculose-1-phosphate aldolase in E-coli.Process Biochemistry,2005.40(2) 707-716.
[75]H.Alper,K.Miyaoku,G.Stephanopoulos.Characterization of lycopene-overproducing E-coli strains in high cell density fermentations.Applied microbiology and biotechnology,2006.72(5) 968-974.
[76]T.Matsui,H.Sato,H.Yamamurob,et al.High cell density cultivation of recombinant Escherichia coli for hirudin variant 1 production.Journal of Biotechnology,2008.134(1-2) 88-92.
[77]S.Yildirim,D.Konrad,S.Calvez,et al.Production of recombinant bacteriocin divercin V41 by high cell density Escherichia coli batch and fed-batch cultures.Applied microbiology and biotechnology,2007.77(3) 525-531.
[78]G.B.Liang,G.C.Du,J.Chen.A novel strategy of enhanced glutathione production in high cell density cultivation of Candida utilis - Cysteine addition combined with dissolved oxygen controlling.Enzyme and Microbial Technology,2008.42(3) 284-289.
[79]H.F.Hang,X.H.Ye,M.J.Guo,et al.A simple fermentation strategy for high-level production of recombinant phytase by Pichia pastoris using glucose as the growth substrate.Enzyme and Microbial Technology,2009.44(4) 185-188.
[80]J.H.Heo,V.Ananin,H.A.Kang,et al.Feeding strategies for the enhanced production of recombinant human serum albumin in the fed-batch cultivation of Hansenula polymorpha.Process Biochemistry,2008.43(9) 918-924.
[81]廖美德.rhbFGF高效表达载体的构建及其重组大肠杆菌高密度培养的研究.[博士学位论文].广州.华南理工大学.2002.125.
[82]S.Ding,T.Tan.1-lactic acid production by Lactobacillus casei fermentation using different fed-batch feeding strategies.Process Biochemistry,2006.41(6) 1451-1454.
[83]W.Zhao,J.Wang,R.Deng,et al.Scare-up fermentation of recombinant Candida rugosa lipase expressed in Pichia pastoris using the GAP promoter.Journal of industrial microbiology &biotechnology,2008.35(3) 189-195.
[84]章越,沈亚领,夏小霞,等.可溶性TRAIL蛋白的高密度培养及补料策略研究.生物工程学报,2004.20(3)408-413.
[85]A.Kern,E.Tilley,I.S.Hunter,et al.Engineering primary metabolic pathways of industrial micro-organisms.Journal of Biotechnology,2007.129(1) 6-29.
[86]M.A.Eiteman,E.Altman.Overcoming acetate in Escherichia coli recombinant protein fermentations.Trends in Biotechnology,2006.24(11) 530-536.
[87]Y.Sevastsyanovich,S.Alfasi,J.Cole.Recombinant protein production:a comparative view on host physiology.New Biotechnology,2009.25(4) 175-180.
[88]M.vandeWalle,J.Shiloach.Proposed mechanism of acetate accumulation in two recombinant Escherichia coli strains during high density fermentation.Biotechnology and Bioengineering,1998.57(1) 71-78.
[89]J.N.Phue,J.Shiloach.Transcription levels of key metabolic genes are the cause for different glucose utilization pathways in E-coli B(BL21) and E-coli K(JM109).Journal of Biotechnology,2004.109(1-2) 21-30.
[90]A.Picon,M.J.T.de Mattos,P.W.Postma.Reducing the glucose uptake rate in Escherichia coli affects growth rate but not protein production.Biotechnology and Bioengineering,2005.90(2) 191-200.
[91]E.Ponce.Effect of growth rate reduction and genetic modifications on acetate accumulation and biomass yields in Escherichia coli.Journal of Bioscience and Bioengineering,1999.87(6) 775-780.
[92]A.R.Lara,C.Vazquez-Limon,G.Gosset,et al.Engineering Escherichia coli to improve culture performance and reduce formation of by-products during recombinant protein production under transient intermittent anaerobic conditions.Biotechnology and Bioengineering,2006.94(6)1164-1175.
[93]A.A.Aristidou,K.Y.San,G.N.Bennett.Metabolic Engineering of Escherichia coli to Enhance Recombinant Protein-Production through Acetate Reduction.Biotechnology Progress,1995.11(4)475-478.
[94]W.R.Farmer,J.C.Liao.Reduction of aerobic acetate production by Escherichia coll.Applied and Environmental Microbiology,1997.63(8) 3205-3210.
[95]J.C.March,M.A.Eiteman,E.Altman.Expression of an anaplerotic enzyme,pyruvate carboxylase,improves recombinant protein production in Escherichia coll.Applied and Environmental Microbiology,2002.68(11) 5620-5624.
[96]G.N.Vemuri,M.A.Eiteman,E.Altman.Increased recombinant protein production in Escherichia coli strains with overexpressed water-forming NADH oxidase and a deleted ArcA regulatory protein.Biotechnology and Bioengineering,2006.94(3) 538-542.
[97]D.Weuster-Botz,H.Paschoid,B.Striegel,et al.Continuous computer controlled production of formate dehydrogenase(FDH) and isolation on a pilot scale.Chemical Engineering & Technology,1994.17(2) 131-137.
[98]D.Weuster-Botz,C.Wandrey.Medium Optimization by Genetic Algorithm for Continuous Production of Formate Dehydrogenase.Process Biochemistry,1995.30(6) 563-571.
[99]Y.L.Bai,S.T.Yang.Production and separation of formate dehydrogenase from Candida boidinii.Enzyme and Microbial Technology,2007.40(4) 940-946.
[100]V.I.Tishkov,A.G.Galkin,V.V.Fedorchuk,et al.Pilot scale production and isolation of recombinant NAD+- and NADP+-specific formate dehydrogenases.Biotechnol Bioeng,1999.64(2) 187-93.
[101]T.Suzuki,H.Idogaki,N.Kasai.A novel generation of optically active ethyl 4-chloro-3-hydroxybutyrate as a C4 chiral building unit using microbial dechlorination.Tetrahedron-Asymmetry,1996.7(11) 3109-3112.
[102]李静.利用重组菌不对称还原4-氯乙酰乙酸乙酯.[硕士学位论文].杭州.浙江大学.2006.65.
[103]刘樱.重组大肠杆菌生物转化法制备手性药物中间体R-(+)-4-氯-3羟基丁酸乙酯.[硕士学位论文].杭州.浙江大学.2005.62.
[104]M.Amidjojo,D.Weuster-Botz.Asymmetric synthesis of the chiral synthon ethyl (S)-4-chloro-3-hydroxybutanoate using Lactobacillus kefir.Tetrahedron-Asymmetry,2005.16(4)899-901.
[105]M.Kataoka,A.Hoshino-Hasegawa,R.Thiwthong,et al.Gene cloning of an NADPH-dependent menadione reductase from Candida macedoniensis,and its application to chiral alcohol production.Enzyme and Microbial Technology,2006.38(7) 944-951.
[106]H.Engelking,R.Pfaller,G.Wich,et al.Reaction engineering studies on beta-ketoester reductions with whole cells of recombinant Saccharomyces cerevisiae.Enzyme and Microbial Technology,2006.38(3-4) 536-544.
[107]K.Kita,M.Kataoka,S.Shimizu.Diversity of 4-chloroacetoacetate ethyl ester-reducing enzymes in yeasts and their application to chiral alcohol synthesis.Journal of Bioscience and Bioengineering,1999.88(6) 591-598.
[108]H.Pfruender,R.Jones,D.Weuster-Botz.Water immiscible ionic liquids as solvents for whole cell biocatalysis.Journal of Biotechnology,2006.124(1) 182-190.
[109]J.Y.He,Z.H.Sun,W.Q.Ruan,et al.Biocatalytic synthesis of ethyl(S)-4-chloro-3-hydroxy-butanoate in an aqueous-organic solvent biphasic system using Aureobasidium pullulans CGMCC 1244.Process Biochemistry,2006.41(1) 244-249.
[110]F.Zhang,Y.Ni,Z.H.Sun,et al.Asymmetric reduction of ethyl 4-chloro-3-oxobutanoate to ethyl (S)-4-chloro-3-hydroxybutanoate catalyzed by Aureobasidium pullulans in an aqueous/ionic liquid biphase system.Chinese Journal of Catalysis,2008.29(6) 577-582.
[111]金勇,吴坚平,徐刚,等.有机相酶催化氨解反应拆分制备(R-4-氯-3-羟基丁酸乙酯).有机化学,2006 26(10)1384-1388.
[112]杨忠华,姚善泾.水相中酵母细胞催化4-氯乙酰乙酸乙酯不对称还原反应.催化学报,2004.25(6)434-438.
[113]李静,林建平,徐志南,等.重组菌转化4-氯乙酰乙酸乙酯为R-(+)-4-氯-3-羟基丁酸乙酯的研究.化学反应工程与工艺,2006.22(4)350-355.
[114]敬科举,徐志南,林建平,等.重组大肠杆菌细胞不对称还原4-氯乙酰乙酸乙酯合成(R)-(+)-4-氯-3-羟基丁酸乙酯.催化学报,2005.26(11)993-998.
[115]Y.Liu,Z.N.Xu,K.J.Jing,et al.Asymmetric reduction of ethyl 4-chloro-3-oxobutanoate to ethyl (R)-4-chloro-3-hydroxybutanoate with two co-existing,recombinant Escherichia coli strains.Biotechnology Letters,2005.27(2) 119-125.
[116]K.J.Jing,Z.N.Xu,Y.Liu,et al.Efficient production of recombinant aldehyde reductase and its application for asymmetric reduction of ethyl 4-chloro-3oxobutanoate to ethyl (R)-4-chloro-3-hydroxybutanoate.Preparative Biochemistry & Biotechnology,2005.35(3) 203-215.
[117]于明安,朱晓冰,祁巍,等.CTAB透性化酵母细胞生物催化合成(S)-(+)-3-羟基丁酸乙酯.催化学报,2005.26(7)609-613.
[118]H.Engelking,R.Pfaller,G.Wich,et al.Stereoselective reduction of ethyl 4-chloro acetoacetate with recombinant Pichia pastoris.Tetrahedron-Asymmetry,2004.15(22) 3591-3593.
[119]J.Y.Houng,J.H.Liao,J.Y.Wu,et al.Enhancement of asymmetric bioreduction of ethyl 4-chloro acetoacetate by the design of composition of culture medium and reaction conditions.Process Biochemistry,2007.42(1) 1-7.
[120]马小魁.酵母菌不对称催化还原4-氯-乙酰乙酸乙醋的研究.[硕士学位论文].西安.西北大学.2004.64.
[121]R.Yang,M.Li,C.Chen.RP-HPLC rapid analysis of organic acids during high cell density culture of recombinant Escherichia coli YK537pSB-TK.Chin J Indust Microbiol,1998.28 29-31.
[122]黄志华,刘铭,王宝光,等.甲酸脱氢酶用于辅酶NADH再生的研究进展 过程工程学报,2006.6(6)1011-1016.
[123]A.Liese,M.Villela.Production of fine chemicals using biocatalysis.Current Opinion in Biotechnology,1999.10(6)595-603.
[124]J.Shiloach,J.Kaufman,A.S.Guillard,et al.Effect of glucose supply strategy on acetate accumulation,growth,and recombinant protein production by Escherichia coli BL21(lambda DE3)and Escherichia coli JM 109.Biotechnology and Bioengineering,1996.49(4) 421-428.
[125]R.S.Donovan,C.W.Robinson,B.R.Glick.Review:Optimizing inducer and culture conditions for expression of foreign proteins under the control of the lac promoter.Journal of Industrial Microbiology,1996.16(3) 145-154.
[126]K.Inoue,Y.Makino,T.Dairi,et al.Gene Cloning and Expression of Leifsonia Alcohol Dehydrogenase(LSADH) Involved in Asymmetric Hydrogen-Transfer Bioreduction to Produce (R)-Form Chiral Alcohols.Bioscience,Biotechnology,and Biochemistry,2006.70(2) 418-426.
[127]H.Yamamoto,K.Mitsuhashi,N.Kimoto,et al.A Novel NADH-Dependent Carbonyl Reductase from Kluyveromyces aestuarii and Comparison of NADH-Regeneration System for the Synthesis of Ethyl(S)-4-Chloro-3-hydroxybutanoate.Bioscience,Biotechnology,and Biochemistry,2004.68(3)638-649.
[128]Y.Yasohara,N.Kizaki,J.Hasegawa,et al.Molecular cloning and overexpression of the gene encoding an NADPH-dependent carbonyl reductase from Candida magnoliae,involved in stereoselective reduction of ethyl 4-chloro-3-oxobutanoate.Bioscience Biotechnology and Biochemistry,2000.64(7) 1430-1436.
[129]N.Kizaki,Y.Yasohara,J.Hasegawa,et al.Synthesis of optically pure ethyl (S)-4-chloro-3-hydroxybutanoate by Escherichia coli transformant cells coexpressing the carbonyl reductase and glucose dehydrogenase genes.Applied microbiology and biotechnology,2001.55(5)590-595.
[130]N.Kizaki,Y.Yasohara,N.Nagashima,et al.Characterization of novel alcohol dehydrogenase of Devosia riboflavina involved in stereoselective reduction of 3-pyrrolidinone derivatives.Journal of Molecular Catalysis B-Enzymatic,2008.51(3-4) 73-80.
[131]A.C.Dahl,M.Fjeldberg,J.O.Madsen.Baker's yeast:improving the D-stereoselectivity in reduction of.3-oxo esters.Tetrahedron-Asymmetry,1999.10(3)551-559.
[132]H.Yamamoto,N.Kimoto,A.Matsuyama,et al.Purification and properties of a carbonyl reductase useful for production of ethyl(S)-4-chloro-3-hydroxybutanoate from Kluyveromyces lactis.Bioscience Biotechnology and Biochemistry,2002.66(8) 1775-1778.
[133]R.N.Patel,C.G.Mcnamee,A.Banerjee,et al.Stereoselective Reduction of Beta-Keto-Esters by Geotrichum-Candidum.Enzyme and Microbial Technology,1992.14(9) 731-738.
[134]N.Itoh,M.Matsuda,M.Mabuchi,et al.Chiral alcohol production by NADH-dependent phenylacetaldehyde reductase coupled with in situ regeneration of NADH.European Journal of Biochemistry,2002.269(9) 2394-2402.
[135]T.Zelinski,J.Peters,M.R.Kula.Purification and Characterization of a Novel Carbonyl Reductase Isolated from Rhodococcus Erythropolis.Journal of Biotechnology,1994.33(3) 283-292.
[136]A.Matsuyama,H.Yamamoto,N.Kawada,et al.Industrial production of(R)-1,3-butanediol by new biocatalysts.Journal of Molecular Catalysis B-Enzymatic,2001.11(4-6) 513-521.
[137]Y.Makino,T.Dairi,N.Itoh.Engineering the phenylacetaldehyde reductase mutant for improved substrate conversion in the presence of concentrated 2-propanol. Applied microbiology and biotechnology, 2007. 77(4) 833-843.
[138] Y. Akakabe, M. Takahashi, M. Kamezawa, et al. Biocatalytic Preparation of Chiral Alcohols by Enantioselective Reduction with Immobilized Cells of Carrot. Journal of the Chemical Society-Perkin Transactions 1,1995(10) 1295-1298.
[139] M. Kataoka, K. Yamamoto, H. Kawabata, et al. Stereoselective reduction of ethyl 4-chloro-3-oxobutanoate by Escherichia coli transformant cells coexpressing the aldehyde reductase and glucose dehydrogenase genes. Applied microbiology and biotechnology, 1999. 51(4) 486-490.
[140] W.R. Shieh, A.S. Gopalan, C.J. Sih. Stereochemical Control of Yeast Reductions .5. Characterization of the Oxidoreductases Involved in the Reduction of Beta-Keto-Esters. Journal of the American Chemical Society, 1985. 107(10)2993-2994.
[2] V.I. Tishkov, V.O. Popov. Protein engineering of formate dehydrogenase. Biomolecular Engineering, 2006.23(2-3)89-110.
[3] V.I. Tishkov, A.G Galkin, V.V. Fedorchuk, et al. Pilot scale production and isolation of recombinant NAD+- and NADP+-specific formate dehydrogenases. Biotechnol Bioeng, 1999. 64(2) 187-193.
[4] V.V. Karzanov, Y.A. Bogatsky, V.I. Tishkov, et al. Evidence for the Presence of a New Nad+-Dependent Formate Dehydrogenase in Pseudomonas Sp-101 Cells Grown on a Molybdenum-Containing Medium. FEMS Microbiology Letters, 1989. 60(2) 197-200.
[5] V.I. Tishkov, V.O. Popov. Catalytic mechanism and application of formate dehydrogenase. Biochemistry (Mosc), 2004. 69(11) 1252-1267.
[6] A. Galkin, L. Kulakova, V. Tishkov, et al. Cloning of formate dehydrogenase gene from a methanol-utilizing bacterium Mycobacterium vaccae N10. Applied microbiology and biotechnology, 1995.44(3-4)479-483.
[7] T. Shinoda, T. Satoh, S. Mineki, et al. Cloning, Nucleotide Sequencing, and Expression in Escherichia coli of the Gene for Formate Dehydrogenase of Paracoccus sp. 12-A, a Formate-assimilating Bacterium. Bioscience, Biotechnology, and Biochemistry, 2002. 66(2) 271-276.
[8] H. Nanba, Y. Takaoka, J. Hasegawa. Purification and characterization of formate dehydrogenase from Ancylobacter aquaticus strain KNK607M, and cloning of the gene. Bioscience Biotechnology and Biochemistry, 2003. 67(4) 720-728.
[9] H. Nanba, Y. Takaoka, J. Hasegawa. Purification and characterization of an alpha-haloketone-resistant formate dehydrogenase from Thiobacillus sp strain KNK65MA, and cloning of the gene. Bioscience Biotechnology and Biochemistry, 2003. 67(10) 2145-2153.
[10] SJ. Allen, J.J. Holbrook. Isolation, sequence and overexpression of the gene encoding NAD-dependent formate dehydrogenase from the methylotrophic yeast Candida methylica. Gene, 1995. 162(1)99-104.
[11] H. Slusarczyk, S. Felber, M.R. Kula, et al. Stabilization of NAD-dependent formate dehydrogenase from Candida boidinii by site-directed mutagenesis of cysteine residues. European Journal of Biochemistry, 2000. 267(5) 1280-1289.
[12] J.E. Galagan, S.E. Calvo, C. Cuomo, et al. Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature, 2005. 438(7071) 1105-1115.
[13] J.E. Galagan, S.E. Calvo, K.A. Borkovich, et al. The genome sequence of the filamentous fungus Neurospora crassa. Nature, 2003. 422(6934) 859-868.
[14] K. Suzuki, R. Itai, K. Suzuki, et al. Formate Dehydrogenase, an Enzyme of Anaerobic Metabolism, Is Induced by Iron Deficiency in Barley Roots.PLANT PHYSIOLOGY,1998.116(2) 725-732.
[15]P.L.Herman,H.Ramberg,R.D.Baack,et al.Formate dehydrogenase in Arabidopsis thaliana:overexpression and subcellular localization in leaves.Plant Science,2002.163(6) 1137-1145.
[16]A.G.Galkin,A.S.Kutsenko,N.P.Bajulina,et al.Site-directed mutagenesis of the essential arginine of the formate dehydrogenase active centre.Biochimica Et Biophysica Acta-Protein Structure and Molecular Enzymoiogy,2002.1594(1) 136-149.
[17]V.O.Popov,V.S.Lamzin.Nad(+)-Dependent Formate Dehydrogenase.Biochemical Journal,1994.301 625-643.
[18]V.I.Tishkov,A.G.Galkin,A.M.Egorov.Kinetic isotope effect and the presteady-state kinetics of the reaction catalyzed by the bacterial formate dehydrogenase.Biochimie,1989.71(4) 551-557.
[19]A.E.Serov,A.S.Popova,V.V.Fedorchuk,et al.Engineering of coenzyme specificity of formate dehydrogenase from Saccharomyces cerevisiae.Biochemical Journal,2002.367 841-847.
[20]K.Seelbach,B.Riebel,W.Hummel,et al.A novel,efficient regenerating method of NADPH using a new formate dehydrogenase.Tetrahedron Letters,1996.37(9) 1377-1380.
[21]A.D.Ellington,J.J.Bull.Evolution.Changing the cofactor diet of an enzyme.Science,2005.310(5747) 454-5.
[22]N.Gul-Karaguler,R.B.Sessions,A.R.Clarke,et al.A single mutation in the NAD-specific formate dehydrogenase from Candida methylica allows the enzyme to use NADP.Biotechnology Letters,2001.23(4) 283-287.
[23]V.I.Tishkov,A.G.Galkin,O.A.Egorova,et al.Site-Directed Mutagenesis of Bacterial Formate Dehydrogenase - Role of Cys-255 in the Enzyme Catalysis and Stability.Doklady Akademii Nauk,1993.328(3) 407-410.
[24]A.M.Rojkova,A.G.Galkin,L.B.Kulakova,et al.Bacterial formate dehydrogenase.Increasing the enzyme thermal stability by hydrophobization of alpha-helices.Febs Letters,1999.445(1) 183-188.
[25]A.E.Serov,E.R.Odintzeva,I.V.Uporov,et al.Use of ramachandran plot for increasing thermal stability of bacterial formate dehydrogenase.Biochemistry-Moscow,2005.70(7) 804-808.
[26]A.V.Mesentsev,V.S.Lamzin,V.I.Tishkov,et al.Effect of pH on kinetic parameters of NAD(+)-dependent formate dehydrogenase.Biochemical Journal,1997.321 475-480.
[27]V.I.Tishkov,A.G.Galkin,A.M.Yegorov.Nad-Dependent Formate Dehydrogenase from Methylotrophic Bacterium Pseudomonas Sp 101 - Cloning,Expression and Study of Gene Structure.Doklady Akademii Nauk Sssr,1991.317(3) 745-748.
[28]S.Heike,F.Stefan,K.Maria-Regina,et al.Candida boidinii formic hydrogenase mutants.Germany.EP1295937(A2).20030326.
[29]R.Li,B.Ziola,J.King.Purification and characterization of formate dehydrogenase from Arabidopsis thaliana.Journal of Plant Physiology,2000.157(2) 161-167.
[30]R.DevauxBasseguy,A.Bergel,M.Comtat.Potential applications of NAD(P)-dependent oxidoreductases in synthesis:A survey.Enzyme and Microbial Technology,1997.20(4) 248-258.
[31]W.Hummel.New alcohol dehydrogenases for the synthesis of chiral compounds.Advances in biochemical engineering/biotechnology,1997.58 145-184.
[32]K.Goldberg,K.Schroer,S.Lutz,et al.Biocatalytic ketone reduction—a powerful tool for the production of chiral alcohols—part Ⅰ:processes with isolated enzymes.Applied microbiology and biotechnology,2007.76(2) 237-248.
[33]W.F.Liu,P.Wang.Cofactor regeneration for sustainable enzymatic biosynthesis.Biotechnology advances,2007.25(4) 369-384.
[34]W.Hummel,M.R.Kula.Dehydrogenases for the Synthesis of Chiral Compounds.European Journal of Biochemistry,1989.184(1)1-13.
[35]K.Nakamura,R.Yamanaka,T.Matsuda,et al.Recent developments in asymmetric reduction of ketones with biocatalysts.Tetrahedron-Asymmetry,2003.14(18) 2659-2681.
[36]P.S.Wagenknecht,J.M.Penney,R.T.Hembre.Transition-metal-catalyzed regeneration of nicotinamide coenzymes with hydrogen.Organometallics,2003.22(6) 1180-1182.
[37]R.Yuan,S.Watanabe,S.Kuwabata,et al.Asymmetric electroreduction of ketone and aldehyde derivatives to the corresponding alcohols using alcohol dehydrogenase as an electrocatalyst.Journal of Organic Chemistry,1997.62(8) 2494-2499.
[38]I.Willner,R.Maidan,M.Shapira.Thermal and Photochemical Regeneration of Nicotinamide Cofactors and a Nicotinamide Model-Compound Using a Water-Soluble Rhodium Phosphine Catalyst.Journal of the Chemical Society-Perkin Transactions 2,1990(4) 559-564.
[39]M.Julliard,J.Lepetit,P.Ritz.Regeneration of Nad+ Cofactor by Photosensitized Electron-Transfer in an Immobilized Alcohol-Dehydrogenase System.Biotechnology and Bioengineering,1986.28(12)1774-1779.
[40]Q.Shi,D.Yang,Z.Jiang,et al.Visible-light photocatalytic regeneration of NADH using P-doped TiO2 nanoparticles.Journal of Molecular Catalysis B:Enzymatic,2006.43(1-4) 44-48.
[41]Z.Findrik,D.Vasic-Racki,S.Lutz,et al.Kinetic modeling of acetophenone reduction catalyzed by alcohol.dehydrogenase from Thermoanaerobacter sp.Biotechnology Letters,2005.27(15)1087-1095.
[42]W.Kroutil,H.Mang,K.Edegger,et al.Recent advances in the biocatalytic reduction of ketones and oxidation of sec-alcohols.Current Opinion in Chemical Biology,2004.8(2) 120-126.
[43]S.Shimizu,M.Kataoka,M.Katoh,et al.Stereoselective Reduction of Ethyl 4-Chloro-3-Oxobutanoate by a Microbial Aldehyde Reductase in an Organic Solvent-Water Diphasic System.Applied and Environmental Microbiology,1990.56(8) 2374-2377.
[44]A.S.Bommarius,M.Schwarm,K.Stingl,et al.Synthesis and use of enantiomericaily pure tert-leucine.Tetrahedron:Asymmetry,1995.6(12) 2851-2888.
[45]R.Wichmann,C.Wandrey,A.F.Buckmann,et al.CONTINUOUS ENZYMATIC TRANSFORMATION IN AN ENZYME MEMBRANE REACTOR WITH SIMULTANEOUS NAD(H) REGENERATION.Biotechnology and Bioengineering,1981.23(12) 2789-2802.
[46]Y.L.Bai,S.T.Yang.Biotransformation of R-2-hydroxy-4-phenylbutyric acid by D-lactate dehydrogenase and Candida boidinii cells containing formate dehydrogenase coimmobilized in a fibrous bed bioreactor.Biotechnology and Bioengineering,2005.92(2) 137-146.
[47]M.Ernst,B.Kaup,M.Muller,et al.Enantioselective reduction of carbonyl compounds by whole-cell biotransformation,combining a formate dehydrogenase and a(R)-specific alcohol dehydrogenase.Applied microbiology and biotechnology,2005.66(6) 629-634.
[48]T.W.Johannes,R.D.Woodyer,H.M.Zhao.Efficient regeneration of NADPH using an engineered phosphite dehydrogenase.Biotechnology and Bioengineering,2007.96(1) 18-26.
[49]M.M.Musa,K.I.Ziegelmann-Fjeld,C.Vieile,et al.Asymmetric reduction and oxidation of aromatic ketones and alcohols using W110A secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus.Journal of Organic Chemistry,2007.72(1) 30-34.
[50]刘子宇,李平兰,郑海涛,等.微生物高密度培养的研究进展.中国乳业,2005(12)47-51.
[51]S.Y.Lee.High cell-density culture of Escherichia coli.Trends in Biotechnology,1996.14(3) 98-105.
[52]D.Riesenberg,R.Guthke.High-cell-density cultivation of microorganisms.Applied microbiology and biotechnology,1999.51(4) 422-430.
[53]李民,陈常庆.重组大肠杆菌高密度发酵研究进展.生物工程进展,2000.20(2)26-31.
[54]A.M.Sanden,I.Prytz,I.Tubulekas,et al.Limiting factors in Escherichia coli fed-batch production of recombinant proteins.Biotechnology and Bioengineering,2003.81(2) 158-66.
[55]P.Neubauer,H.Y.Lin,B.Mathiszik.Metabolic load of recombinant protein production:Inhibition of cellular capacities for glucose uptake and respiration after induction of a heteroiogous gene in Escherichia coli.Biotechnology and Bioengineering,2003.83(1) 53-64.
[56]A.M.Sanden,I.Prytz,I.Tubulekas,et al.Limiting factors in Escherichia coli fed-batch production of recombinant proteins.Biotechnology and Bioengineering,2003.81(2) 158-166.
[57]T.Suzuki.A dense cell culture system for microorganisms using a stirred ceramic membrane reactor incorporating asymmetric porous ceramic filters.Journal of Fermentation and Bioengineering,1996.82(3) 264-271.
[58]K.Nakano,M.Rischke,S.Sato,et al.Influence of acetic acid on the growth of Escherichia coli K12during high-cell-density cultivation in a dialysis reactor.Applied microbiology and biotechnology,1997.48(5) 597-601.
[59]J.Shiloach,R.Fass.Growing E-coli to high cell density - A historical perspective on method development.Biotechnology Advances,2005.23(5) 345-357.
[60]L.C.Cheng,J.Y.Wu,T.L.Chen.A pseudo-exponential feeding method for control of specific growth rate in fed-batch cultures.Biochemical Engineering Journal,2002.10(3) 227-232.
[61]S.S.Yazdani,A.R.Shakri,C.E.Chitnis.A high cell density fermentation strategy to produce recombinant malarial antigen in E-coli.Biotechnology Letters,2004.26(24) 1891-1895.
[62]B.Kim,S.Lee,S.Lee,et al.High cell density fed-batch cultivation of Escherichia coli using exponential feeding combined with pH-stat.Bioprocess and Biosystems Engineering,2004.26(3)147-150.
[63]R.Khalilzadeh,S.A.Shojaosadati,A.Bahrami,et al.Over-expression of recombinant human interferon-gamma in high cell density fermentation of Escherichia coli.Biotechnology Letters,2003. 25(23) 1989-1992.
[64]V.S.Whiffin,M.J.Cooney,R.Cord-Ruwisch.Online detection of feed demand in high cell density cultures of Escherichia coli by measurement of changes in dissolved oxygen transients in complex media.Biotechnology and Bioengineering,2004.85(4) 422-433.
[65]M.Akesson,P.Hagander,J.P.Axelsson.Avoiding acetate accumulation in Escherichia coli cultures using feedback control of glucose feeding,Biotechnology and Bioengineering,2001.73(3) 223-230.
[66]E.A.Sandoval-Basurto,G.Gosset,F.Bolivar,et al.Culture of Escherichia coli under dissolved oxygen gradients simulated in a two-compartment scale-down system:Metabolic response and production of recombinant protein.Biotechnology and Bioengineering,2005.89(4) 453-463.
[67]T.Matsui,N.Shinzato,H.Yokota,et al.High cell density cultivation of recombinant E-coli with a pressurized culture.Process Biochemistry,2006.41(4) 920-924.
[68]M.Akesson,E.N.Karisson,P.Hagander,et al.On-line detection of acetate formation in Escherichia coli cultures using dissolved oxygen responses to feed transients.Biotechnology and Bioengineering,1999.64(5) 590-598.
[69]U.Horn,W.Strittmarter,A.Krebber,et al.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.Applied microbiology and biotechnology,1996.46(5-6) 524-532.
[70]李民,陈常庆,朴勤,等.利用恒溶氧-补料分批技术高密度培养大肠杆菌生产重组人骨形成蛋白-2A.生物工程学报,1998.14(3)270-275.
[71]K.R.Babu,S.Swaminathan,S.Marten,et al.Production of interferon-α in high cell density cultures of recombinant Escherichia coli and its single step purification from refolded inclusion body proteins Applied microbiology and biotechnology,2000.53(6) 655-660.
[72]J.Qiu,J.R.Swartz,G.Georgiou.Expression of active human tissue-type plasminogen activator in Escherichia coli.Applied and Environmental Microbiology,1998.64(12) 4891-4896.
[73]J.Pinsach,C.de Mas,J.Lopez-Santin.A simple feedback control of Escherichia coli growth for recombinant aidolase production in fed-batch mode.Biochemical Engineering Journal,2006.29(3)235-242.
[74]O.Durany,C.de Mas,J.Lopez-Santin.Fed-batch production of recombinant fuculose-1-phosphate aldolase in E-coli.Process Biochemistry,2005.40(2) 707-716.
[75]H.Alper,K.Miyaoku,G.Stephanopoulos.Characterization of lycopene-overproducing E-coli strains in high cell density fermentations.Applied microbiology and biotechnology,2006.72(5) 968-974.
[76]T.Matsui,H.Sato,H.Yamamurob,et al.High cell density cultivation of recombinant Escherichia coli for hirudin variant 1 production.Journal of Biotechnology,2008.134(1-2) 88-92.
[77]S.Yildirim,D.Konrad,S.Calvez,et al.Production of recombinant bacteriocin divercin V41 by high cell density Escherichia coli batch and fed-batch cultures.Applied microbiology and biotechnology,2007.77(3) 525-531.
[78]G.B.Liang,G.C.Du,J.Chen.A novel strategy of enhanced glutathione production in high cell density cultivation of Candida utilis - Cysteine addition combined with dissolved oxygen controlling.Enzyme and Microbial Technology,2008.42(3) 284-289.
[79]H.F.Hang,X.H.Ye,M.J.Guo,et al.A simple fermentation strategy for high-level production of recombinant phytase by Pichia pastoris using glucose as the growth substrate.Enzyme and Microbial Technology,2009.44(4) 185-188.
[80]J.H.Heo,V.Ananin,H.A.Kang,et al.Feeding strategies for the enhanced production of recombinant human serum albumin in the fed-batch cultivation of Hansenula polymorpha.Process Biochemistry,2008.43(9) 918-924.
[81]廖美德.rhbFGF高效表达载体的构建及其重组大肠杆菌高密度培养的研究.[博士学位论文].广州.华南理工大学.2002.125.
[82]S.Ding,T.Tan.1-lactic acid production by Lactobacillus casei fermentation using different fed-batch feeding strategies.Process Biochemistry,2006.41(6) 1451-1454.
[83]W.Zhao,J.Wang,R.Deng,et al.Scare-up fermentation of recombinant Candida rugosa lipase expressed in Pichia pastoris using the GAP promoter.Journal of industrial microbiology &biotechnology,2008.35(3) 189-195.
[84]章越,沈亚领,夏小霞,等.可溶性TRAIL蛋白的高密度培养及补料策略研究.生物工程学报,2004.20(3)408-413.
[85]A.Kern,E.Tilley,I.S.Hunter,et al.Engineering primary metabolic pathways of industrial micro-organisms.Journal of Biotechnology,2007.129(1) 6-29.
[86]M.A.Eiteman,E.Altman.Overcoming acetate in Escherichia coli recombinant protein fermentations.Trends in Biotechnology,2006.24(11) 530-536.
[87]Y.Sevastsyanovich,S.Alfasi,J.Cole.Recombinant protein production:a comparative view on host physiology.New Biotechnology,2009.25(4) 175-180.
[88]M.vandeWalle,J.Shiloach.Proposed mechanism of acetate accumulation in two recombinant Escherichia coli strains during high density fermentation.Biotechnology and Bioengineering,1998.57(1) 71-78.
[89]J.N.Phue,J.Shiloach.Transcription levels of key metabolic genes are the cause for different glucose utilization pathways in E-coli B(BL21) and E-coli K(JM109).Journal of Biotechnology,2004.109(1-2) 21-30.
[90]A.Picon,M.J.T.de Mattos,P.W.Postma.Reducing the glucose uptake rate in Escherichia coli affects growth rate but not protein production.Biotechnology and Bioengineering,2005.90(2) 191-200.
[91]E.Ponce.Effect of growth rate reduction and genetic modifications on acetate accumulation and biomass yields in Escherichia coli.Journal of Bioscience and Bioengineering,1999.87(6) 775-780.
[92]A.R.Lara,C.Vazquez-Limon,G.Gosset,et al.Engineering Escherichia coli to improve culture performance and reduce formation of by-products during recombinant protein production under transient intermittent anaerobic conditions.Biotechnology and Bioengineering,2006.94(6)1164-1175.
[93]A.A.Aristidou,K.Y.San,G.N.Bennett.Metabolic Engineering of Escherichia coli to Enhance Recombinant Protein-Production through Acetate Reduction.Biotechnology Progress,1995.11(4)475-478.
[94]W.R.Farmer,J.C.Liao.Reduction of aerobic acetate production by Escherichia coll.Applied and Environmental Microbiology,1997.63(8) 3205-3210.
[95]J.C.March,M.A.Eiteman,E.Altman.Expression of an anaplerotic enzyme,pyruvate carboxylase,improves recombinant protein production in Escherichia coll.Applied and Environmental Microbiology,2002.68(11) 5620-5624.
[96]G.N.Vemuri,M.A.Eiteman,E.Altman.Increased recombinant protein production in Escherichia coli strains with overexpressed water-forming NADH oxidase and a deleted ArcA regulatory protein.Biotechnology and Bioengineering,2006.94(3) 538-542.
[97]D.Weuster-Botz,H.Paschoid,B.Striegel,et al.Continuous computer controlled production of formate dehydrogenase(FDH) and isolation on a pilot scale.Chemical Engineering & Technology,1994.17(2) 131-137.
[98]D.Weuster-Botz,C.Wandrey.Medium Optimization by Genetic Algorithm for Continuous Production of Formate Dehydrogenase.Process Biochemistry,1995.30(6) 563-571.
[99]Y.L.Bai,S.T.Yang.Production and separation of formate dehydrogenase from Candida boidinii.Enzyme and Microbial Technology,2007.40(4) 940-946.
[100]V.I.Tishkov,A.G.Galkin,V.V.Fedorchuk,et al.Pilot scale production and isolation of recombinant NAD+- and NADP+-specific formate dehydrogenases.Biotechnol Bioeng,1999.64(2) 187-93.
[101]T.Suzuki,H.Idogaki,N.Kasai.A novel generation of optically active ethyl 4-chloro-3-hydroxybutyrate as a C4 chiral building unit using microbial dechlorination.Tetrahedron-Asymmetry,1996.7(11) 3109-3112.
[102]李静.利用重组菌不对称还原4-氯乙酰乙酸乙酯.[硕士学位论文].杭州.浙江大学.2006.65.
[103]刘樱.重组大肠杆菌生物转化法制备手性药物中间体R-(+)-4-氯-3羟基丁酸乙酯.[硕士学位论文].杭州.浙江大学.2005.62.
[104]M.Amidjojo,D.Weuster-Botz.Asymmetric synthesis of the chiral synthon ethyl (S)-4-chloro-3-hydroxybutanoate using Lactobacillus kefir.Tetrahedron-Asymmetry,2005.16(4)899-901.
[105]M.Kataoka,A.Hoshino-Hasegawa,R.Thiwthong,et al.Gene cloning of an NADPH-dependent menadione reductase from Candida macedoniensis,and its application to chiral alcohol production.Enzyme and Microbial Technology,2006.38(7) 944-951.
[106]H.Engelking,R.Pfaller,G.Wich,et al.Reaction engineering studies on beta-ketoester reductions with whole cells of recombinant Saccharomyces cerevisiae.Enzyme and Microbial Technology,2006.38(3-4) 536-544.
[107]K.Kita,M.Kataoka,S.Shimizu.Diversity of 4-chloroacetoacetate ethyl ester-reducing enzymes in yeasts and their application to chiral alcohol synthesis.Journal of Bioscience and Bioengineering,1999.88(6) 591-598.
[108]H.Pfruender,R.Jones,D.Weuster-Botz.Water immiscible ionic liquids as solvents for whole cell biocatalysis.Journal of Biotechnology,2006.124(1) 182-190.
[109]J.Y.He,Z.H.Sun,W.Q.Ruan,et al.Biocatalytic synthesis of ethyl(S)-4-chloro-3-hydroxy-butanoate in an aqueous-organic solvent biphasic system using Aureobasidium pullulans CGMCC 1244.Process Biochemistry,2006.41(1) 244-249.
[110]F.Zhang,Y.Ni,Z.H.Sun,et al.Asymmetric reduction of ethyl 4-chloro-3-oxobutanoate to ethyl (S)-4-chloro-3-hydroxybutanoate catalyzed by Aureobasidium pullulans in an aqueous/ionic liquid biphase system.Chinese Journal of Catalysis,2008.29(6) 577-582.
[111]金勇,吴坚平,徐刚,等.有机相酶催化氨解反应拆分制备(R-4-氯-3-羟基丁酸乙酯).有机化学,2006 26(10)1384-1388.
[112]杨忠华,姚善泾.水相中酵母细胞催化4-氯乙酰乙酸乙酯不对称还原反应.催化学报,2004.25(6)434-438.
[113]李静,林建平,徐志南,等.重组菌转化4-氯乙酰乙酸乙酯为R-(+)-4-氯-3-羟基丁酸乙酯的研究.化学反应工程与工艺,2006.22(4)350-355.
[114]敬科举,徐志南,林建平,等.重组大肠杆菌细胞不对称还原4-氯乙酰乙酸乙酯合成(R)-(+)-4-氯-3-羟基丁酸乙酯.催化学报,2005.26(11)993-998.
[115]Y.Liu,Z.N.Xu,K.J.Jing,et al.Asymmetric reduction of ethyl 4-chloro-3-oxobutanoate to ethyl (R)-4-chloro-3-hydroxybutanoate with two co-existing,recombinant Escherichia coli strains.Biotechnology Letters,2005.27(2) 119-125.
[116]K.J.Jing,Z.N.Xu,Y.Liu,et al.Efficient production of recombinant aldehyde reductase and its application for asymmetric reduction of ethyl 4-chloro-3oxobutanoate to ethyl (R)-4-chloro-3-hydroxybutanoate.Preparative Biochemistry & Biotechnology,2005.35(3) 203-215.
[117]于明安,朱晓冰,祁巍,等.CTAB透性化酵母细胞生物催化合成(S)-(+)-3-羟基丁酸乙酯.催化学报,2005.26(7)609-613.
[118]H.Engelking,R.Pfaller,G.Wich,et al.Stereoselective reduction of ethyl 4-chloro acetoacetate with recombinant Pichia pastoris.Tetrahedron-Asymmetry,2004.15(22) 3591-3593.
[119]J.Y.Houng,J.H.Liao,J.Y.Wu,et al.Enhancement of asymmetric bioreduction of ethyl 4-chloro acetoacetate by the design of composition of culture medium and reaction conditions.Process Biochemistry,2007.42(1) 1-7.
[120]马小魁.酵母菌不对称催化还原4-氯-乙酰乙酸乙醋的研究.[硕士学位论文].西安.西北大学.2004.64.
[121]R.Yang,M.Li,C.Chen.RP-HPLC rapid analysis of organic acids during high cell density culture of recombinant Escherichia coli YK537pSB-TK.Chin J Indust Microbiol,1998.28 29-31.
[122]黄志华,刘铭,王宝光,等.甲酸脱氢酶用于辅酶NADH再生的研究进展 过程工程学报,2006.6(6)1011-1016.
[123]A.Liese,M.Villela.Production of fine chemicals using biocatalysis.Current Opinion in Biotechnology,1999.10(6)595-603.
[124]J.Shiloach,J.Kaufman,A.S.Guillard,et al.Effect of glucose supply strategy on acetate accumulation,growth,and recombinant protein production by Escherichia coli BL21(lambda DE3)and Escherichia coli JM 109.Biotechnology and Bioengineering,1996.49(4) 421-428.
[125]R.S.Donovan,C.W.Robinson,B.R.Glick.Review:Optimizing inducer and culture conditions for expression of foreign proteins under the control of the lac promoter.Journal of Industrial Microbiology,1996.16(3) 145-154.
[126]K.Inoue,Y.Makino,T.Dairi,et al.Gene Cloning and Expression of Leifsonia Alcohol Dehydrogenase(LSADH) Involved in Asymmetric Hydrogen-Transfer Bioreduction to Produce (R)-Form Chiral Alcohols.Bioscience,Biotechnology,and Biochemistry,2006.70(2) 418-426.
[127]H.Yamamoto,K.Mitsuhashi,N.Kimoto,et al.A Novel NADH-Dependent Carbonyl Reductase from Kluyveromyces aestuarii and Comparison of NADH-Regeneration System for the Synthesis of Ethyl(S)-4-Chloro-3-hydroxybutanoate.Bioscience,Biotechnology,and Biochemistry,2004.68(3)638-649.
[128]Y.Yasohara,N.Kizaki,J.Hasegawa,et al.Molecular cloning and overexpression of the gene encoding an NADPH-dependent carbonyl reductase from Candida magnoliae,involved in stereoselective reduction of ethyl 4-chloro-3-oxobutanoate.Bioscience Biotechnology and Biochemistry,2000.64(7) 1430-1436.
[129]N.Kizaki,Y.Yasohara,J.Hasegawa,et al.Synthesis of optically pure ethyl (S)-4-chloro-3-hydroxybutanoate by Escherichia coli transformant cells coexpressing the carbonyl reductase and glucose dehydrogenase genes.Applied microbiology and biotechnology,2001.55(5)590-595.
[130]N.Kizaki,Y.Yasohara,N.Nagashima,et al.Characterization of novel alcohol dehydrogenase of Devosia riboflavina involved in stereoselective reduction of 3-pyrrolidinone derivatives.Journal of Molecular Catalysis B-Enzymatic,2008.51(3-4) 73-80.
[131]A.C.Dahl,M.Fjeldberg,J.O.Madsen.Baker's yeast:improving the D-stereoselectivity in reduction of.3-oxo esters.Tetrahedron-Asymmetry,1999.10(3)551-559.
[132]H.Yamamoto,N.Kimoto,A.Matsuyama,et al.Purification and properties of a carbonyl reductase useful for production of ethyl(S)-4-chloro-3-hydroxybutanoate from Kluyveromyces lactis.Bioscience Biotechnology and Biochemistry,2002.66(8) 1775-1778.
[133]R.N.Patel,C.G.Mcnamee,A.Banerjee,et al.Stereoselective Reduction of Beta-Keto-Esters by Geotrichum-Candidum.Enzyme and Microbial Technology,1992.14(9) 731-738.
[134]N.Itoh,M.Matsuda,M.Mabuchi,et al.Chiral alcohol production by NADH-dependent phenylacetaldehyde reductase coupled with in situ regeneration of NADH.European Journal of Biochemistry,2002.269(9) 2394-2402.
[135]T.Zelinski,J.Peters,M.R.Kula.Purification and Characterization of a Novel Carbonyl Reductase Isolated from Rhodococcus Erythropolis.Journal of Biotechnology,1994.33(3) 283-292.
[136]A.Matsuyama,H.Yamamoto,N.Kawada,et al.Industrial production of(R)-1,3-butanediol by new biocatalysts.Journal of Molecular Catalysis B-Enzymatic,2001.11(4-6) 513-521.
[137]Y.Makino,T.Dairi,N.Itoh.Engineering the phenylacetaldehyde reductase mutant for improved substrate conversion in the presence of concentrated 2-propanol. Applied microbiology and biotechnology, 2007. 77(4) 833-843.
[138] Y. Akakabe, M. Takahashi, M. Kamezawa, et al. Biocatalytic Preparation of Chiral Alcohols by Enantioselective Reduction with Immobilized Cells of Carrot. Journal of the Chemical Society-Perkin Transactions 1,1995(10) 1295-1298.
[139] M. Kataoka, K. Yamamoto, H. Kawabata, et al. Stereoselective reduction of ethyl 4-chloro-3-oxobutanoate by Escherichia coli transformant cells coexpressing the aldehyde reductase and glucose dehydrogenase genes. Applied microbiology and biotechnology, 1999. 51(4) 486-490.
[140] W.R. Shieh, A.S. Gopalan, C.J. Sih. Stereochemical Control of Yeast Reductions .5. Characterization of the Oxidoreductases Involved in the Reduction of Beta-Keto-Esters. Journal of the American Chemical Society, 1985. 107(10)2993-2994.