生物法生产1，3-二羟基丙酮产品研究
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摘要
随着石油资源日益枯竭,工业模式逐渐由石油炼制向生物炼制转变。本文针对甘油生物炼制1,3-二羟基丙酮(DHA)过程中存在的底物投料浓度低、DHA生产效率低及后续提取分离工序复杂、收得率低等问题,对氧化葡萄糖酸杆菌(Gluconobacter oxydans)转化甘油生产DHA进行了产品开发研究。
为提高Gluconobacter oxydans (G. oxydans)转化甘油生产DHA的能力,利用He-Ne激光辐照该菌,在21 mW 19~21 min剂量范围内,获得了较高的正突变率。通过甘油和DHA耐受性筛选,最终获得具有高DHA生产能力和稳定遗传特性的正突变株GM51。通过对GM51和出发菌株的性能对比研究,甘油初始浓度为100 g/L时,GM51中甘油脱氢酶活力比出发菌株提高了75.17%;7 L发酵罐中发酵周期缩短了10~15 h,DHA对甘油的得率达到了92%,比出发菌株提高了77.6%,体积生产速率由1.29 g·L-1·h-1提高到了2.29 g·L-1·h-1。
在单因素实验结果基础上,采用响应曲面法确定了最佳发酵培养基组成(g/L)为:酵母膏2.39,蛋白胨2.18,甘油100.0,(NH4)2SO4 2.0,MgSO4·7H2O 1.0,K2HPO4·3H2O 2.62,MnSO4·1H2O 0.53,CaCO3 2.5,CaCl2 1.25。培养条件:接种量5%,初始pH5.9,摇床转速210 rpm,培养时间45 h。在最佳条件下进行G. oxydans GM51发酵,DHA的产量为82.81 g/L,比优化前提高了41%。
在7 L发酵罐中考察了DHA间歇发酵、分批补料发酵和流加发酵特征。实验表明,分批补料发酵可解决间歇发酵后期营养物质耗竭导致的DHA合成受限问题;连续补料发酵可弥补分批补料发酵引起的发酵液环境参数的瞬间剧烈变化,使DHA产量达到123.8 g/L,较间歇发酵提高约36%。建立了适当的G. oxydans GM51间歇发酵生产DHA过程中菌体生长、底物消耗及产物生成动力学模型,并可较准确的预测发酵过程中细胞生物量、产物和底物的变化趋势。
利用天然高分子絮凝剂壳聚糖和活性炭对DHA发酵液进行预处理后,醇沉去除发酵液中蛋白、核酸、多糖等大分子及盐,实验结果显示,经上述工艺后菌体和蛋白的去除率分别达到100%和98.6%,处理前后溶液总电导率下降96.4%,DHA损失8.6%。经乙醇中溶析结晶后DHA的结晶得率为81%。采用以上确定的整个提取分离工艺,所得DHA成品的收得率大于72%,纯度达99.8%,达到了市售商品质量规格要求。
With the depletion of petroleum resources, petroleum refining is being replaced by biorefining gradually. To solve the problems during the production of 1,3-dihydroxyacetone (DHA) from glycerol by biorefinery such as low initial substrate concentration, low production efficiency, complicated subsequent extraction process, low DHA yield and so on, the whole production technology of DHA from glycerol by Gluconobacter oxydans has been researched in this work.
In order to increase the DHA production capacity of G. oxydans from glycerol, He-Ne laser was used to irradiate G. oxydans and among the dose range of 21 mW 19~21 min, higher positive mutant rate could be obtained. After the tolerance experiment of glycerol and DHA, mutant G. oxydans GM51 with high DHA production capacity and stable heredity was obtained finally. By comparison the performance of mutant GM51 and wild strain, the activity of glycerol dehydrogenase in GM51 was 75.17% higher than that in wild strain when the initial glycerol concentration was 100 g/L. The culture cyclic of mutant GM51 had been shortened by 10~15 hours and the yield of DHA had been increased by 77.6% during the culture in 7 L fermenter. The DHA productivity had been improved from 1.29 g·L-1·h-1 to 2.29 g·L-1·h-1.
Based on the experimental results of single factor, response surface methodology was used to determine the optimal fermentation medium composition (g/L): yeast extract 2.39, peptone 2.18, glycerol 100.0, (NH4)2SO4 2.0, MgSO4·7H2O 1.0, K2HPO4·3H2O 2.62, MnSO4·1H2O 0.53, CaCO3 2.5, CaCl2 1.25; inoculum concentration 5% (v/v), initial pH 5.9, rotational speed of the cradle 210 rpm, culture time 45 h. Under the optimal conditions, the yield of DHA was 82.81 g/L by mutant GM51, which was 41% higher than that before optimization.
The characteristics of batch, semi-fed-batch and fed-batch fermentation in a 7 L bioreactor were investigated. In the late phase of the batch fermentation, DHA biosynthesis would be repressed due to the exhaustion of nutrition substances. Semi-fed-batch could improve the substrate supply and increase DHA productivity. Fed-batch fermentation could prevent the dramatic transient phenomenon in fermentation environment aroused by semi-fed-batch culture; therefore the DHA yield was further increased by about 36% to 123.8 g/L. A proper kinetic model for cell growth, substrate consumption and DHA formation by mutant GM51 was established and it could predict the variation tendency of biomass, substrate and product correctly.
Natural macromolecular flocculant—chitosan was used to remove cell and protein and absorbent charcoal was used to remove the pigment in the fermentation broth. Protein, nucleic acid, polyoses and salt were removed further by alcohol precipitation. The experimental results indicated that 100% cell and 98.6% protein were removed respectively through the above process, and most salt was separated and removed by crystallization with 96.4% decrease of the total conductivity. Meanwhile, DHA loss was 8.6% during the process. After crystallization in alcohol, the crystallization yield of DHA was 81%. By using the above separation technology, the yield of DHA was more than 72% and the purity of DHA was up to 99.8%. And the DHA product produced in this work has been met the quality requirements compared with DHA of commercial grade.
为提高Gluconobacter oxydans (G. oxydans)转化甘油生产DHA的能力,利用He-Ne激光辐照该菌,在21 mW 19~21 min剂量范围内,获得了较高的正突变率。通过甘油和DHA耐受性筛选,最终获得具有高DHA生产能力和稳定遗传特性的正突变株GM51。通过对GM51和出发菌株的性能对比研究,甘油初始浓度为100 g/L时,GM51中甘油脱氢酶活力比出发菌株提高了75.17%;7 L发酵罐中发酵周期缩短了10~15 h,DHA对甘油的得率达到了92%,比出发菌株提高了77.6%,体积生产速率由1.29 g·L-1·h-1提高到了2.29 g·L-1·h-1。
在单因素实验结果基础上,采用响应曲面法确定了最佳发酵培养基组成(g/L)为:酵母膏2.39,蛋白胨2.18,甘油100.0,(NH4)2SO4 2.0,MgSO4·7H2O 1.0,K2HPO4·3H2O 2.62,MnSO4·1H2O 0.53,CaCO3 2.5,CaCl2 1.25。培养条件:接种量5%,初始pH5.9,摇床转速210 rpm,培养时间45 h。在最佳条件下进行G. oxydans GM51发酵,DHA的产量为82.81 g/L,比优化前提高了41%。
在7 L发酵罐中考察了DHA间歇发酵、分批补料发酵和流加发酵特征。实验表明,分批补料发酵可解决间歇发酵后期营养物质耗竭导致的DHA合成受限问题;连续补料发酵可弥补分批补料发酵引起的发酵液环境参数的瞬间剧烈变化,使DHA产量达到123.8 g/L,较间歇发酵提高约36%。建立了适当的G. oxydans GM51间歇发酵生产DHA过程中菌体生长、底物消耗及产物生成动力学模型,并可较准确的预测发酵过程中细胞生物量、产物和底物的变化趋势。
利用天然高分子絮凝剂壳聚糖和活性炭对DHA发酵液进行预处理后,醇沉去除发酵液中蛋白、核酸、多糖等大分子及盐,实验结果显示,经上述工艺后菌体和蛋白的去除率分别达到100%和98.6%,处理前后溶液总电导率下降96.4%,DHA损失8.6%。经乙醇中溶析结晶后DHA的结晶得率为81%。采用以上确定的整个提取分离工艺,所得DHA成品的收得率大于72%,纯度达99.8%,达到了市售商品质量规格要求。
With the depletion of petroleum resources, petroleum refining is being replaced by biorefining gradually. To solve the problems during the production of 1,3-dihydroxyacetone (DHA) from glycerol by biorefinery such as low initial substrate concentration, low production efficiency, complicated subsequent extraction process, low DHA yield and so on, the whole production technology of DHA from glycerol by Gluconobacter oxydans has been researched in this work.
In order to increase the DHA production capacity of G. oxydans from glycerol, He-Ne laser was used to irradiate G. oxydans and among the dose range of 21 mW 19~21 min, higher positive mutant rate could be obtained. After the tolerance experiment of glycerol and DHA, mutant G. oxydans GM51 with high DHA production capacity and stable heredity was obtained finally. By comparison the performance of mutant GM51 and wild strain, the activity of glycerol dehydrogenase in GM51 was 75.17% higher than that in wild strain when the initial glycerol concentration was 100 g/L. The culture cyclic of mutant GM51 had been shortened by 10~15 hours and the yield of DHA had been increased by 77.6% during the culture in 7 L fermenter. The DHA productivity had been improved from 1.29 g·L-1·h-1 to 2.29 g·L-1·h-1.
Based on the experimental results of single factor, response surface methodology was used to determine the optimal fermentation medium composition (g/L): yeast extract 2.39, peptone 2.18, glycerol 100.0, (NH4)2SO4 2.0, MgSO4·7H2O 1.0, K2HPO4·3H2O 2.62, MnSO4·1H2O 0.53, CaCO3 2.5, CaCl2 1.25; inoculum concentration 5% (v/v), initial pH 5.9, rotational speed of the cradle 210 rpm, culture time 45 h. Under the optimal conditions, the yield of DHA was 82.81 g/L by mutant GM51, which was 41% higher than that before optimization.
The characteristics of batch, semi-fed-batch and fed-batch fermentation in a 7 L bioreactor were investigated. In the late phase of the batch fermentation, DHA biosynthesis would be repressed due to the exhaustion of nutrition substances. Semi-fed-batch could improve the substrate supply and increase DHA productivity. Fed-batch fermentation could prevent the dramatic transient phenomenon in fermentation environment aroused by semi-fed-batch culture; therefore the DHA yield was further increased by about 36% to 123.8 g/L. A proper kinetic model for cell growth, substrate consumption and DHA formation by mutant GM51 was established and it could predict the variation tendency of biomass, substrate and product correctly.
Natural macromolecular flocculant—chitosan was used to remove cell and protein and absorbent charcoal was used to remove the pigment in the fermentation broth. Protein, nucleic acid, polyoses and salt were removed further by alcohol precipitation. The experimental results indicated that 100% cell and 98.6% protein were removed respectively through the above process, and most salt was separated and removed by crystallization with 96.4% decrease of the total conductivity. Meanwhile, DHA loss was 8.6% during the process. After crystallization in alcohol, the crystallization yield of DHA was 81%. By using the above separation technology, the yield of DHA was more than 72% and the purity of DHA was up to 99.8%. And the DHA product produced in this work has been met the quality requirements compared with DHA of commercial grade.
引文
[1] ?lepokura K, Lis T, Crystal structures of dihydroxyacetone and its derivatives, Carbohydrate Research, 339 (11): 1995-2007.
[2]李尧,微生物发酵生产二羟基丙酮的应用研究进展,四川食品与发酵,2007,43 (139): 20-23.
[3] Sommer K, Bohlmann U, Bohnet M, Production of Dihydroxyacetone in a Three Phase Fluidized Bed Reactor Using Gluconobacter Oxydans, Chem. Eng. Technol., 1998, 21(2): 144-149.
[4] Bicker M, Endres S, Ott L, Vogel H, Catalytical conversion of carbohydrates in subcritical water: A new chemical process for lactic acid production, J. Mol. Catal. A-Chem., 2005, 239 (1-2): 151-157.
[5] Murga J, Falomir E, Carda M, et al., Chlorodicyclohexylborane-Mediated Aldol Additions ofα,α‘-Dioxygenated Ketones, Org. Lett. 2001, 3 (6): 901-904.
[6] Kim K S, Hong S D, Synthesis and stereoselective aldol reaction of dihydroxyacetone derivatives, Tetrahedron Lett. 2000, 41 (31): 5909-5913.
[7] Enders D, Voith M, Lenzen A, The Dihydroxyacetone Unit—A Versatile C3 Building Block in Organic Synthesis, Angew. Chem. Int. Ed., 2005, 44: 1304-1325.
[8] Tamura Y, Yakura T, Haruta J I, An efficient conversion of keto groups into dihydroxyacetone groups: Oxidation of ethynylcarbinol intermediates by using hypervalent iodine reagent, Tetrahedron Letters, 1985, 26 (32): 3837-3840.
[9] Schmincke H, Hoppe D, Studies toward the total synthesis of 1-oxacephalosporins 3: synthesis of a (±)-trans-7-benzoylamino-3-carbamoyloxymethyl-1-oxa-3-cepheh -3-carboxylate from 1,3-dihydroxyacetone, Tetrahedron, 1989, 45 (3): 701-707.
[10] Waagen V, Partali V, Hollingster I, et al., Dihydroxyacetone dimers; solution and crystal structure of stereoisomers of 2,5-diethoxy-1,4-dioxane-2,5-dimethanol, Tetrahedron, 1994, 50 (33): 10055-10060.
[11] Araki Y, Nagasawa J I, Ishido Y, Synthetic studies of carbohydrate derivatives by photochemical reactions. Part 16. Synthesis of DL-apiose derivatives by photochemical cycloaddition of 1,3-dihydroxypropan-2-one derivatives with ethenediol or ethenol derivatives, J. Chem. Soc. Perkin Trans. 1, 1981, 12-23.
[12] Olsen R K, Feng X, Campbell M, et al., Synthesis of Functionalized Aryloxy 1,3-Butadienes and Their Transformation to Diaryl Ethers via Diels-Alder Cycloaddition Reactions, J. Org. Chem. 1995, 60 (19): 6025-6031.
[13] Walker L F, Connolly S, Wills M, Synthesis of 2,5-dihydrofurans via alkylidene carbene insertion reactions, Tetrahedron Lett. 1998, 39 (29): 5273-5276.
[14] Shimada S, Hashimoto Y, Nagashima T, et al., Diastereoselective ring-opening aldol-type reaction of 2,2-dialkoxycyclopropanecarboxylic esters with carbonyl compounds. 2. Synthesis of cis-2,3-substituted-γ-lactones, Tetrahedron 1993, 49 (8): 1589-1604.
[15] Fujiwara K, Amano A, Tokiwano T, Novel Oxepane Formation by TiCl4-Catalyzed Nucleophilic Cleavage of 1-Alkoxymethyl-6,8-dioxabicyclo [3.2.1] octanes, Tetrahedron 2000, 56 (8): 1065-1080.
[16]汪连生,程巳雪,卓仁禧,从二羟基丙酮出发合成新型聚碳酸酯[EB/OL], http://www.polymer.cn,2004-11-14.
[17] Brown D A, Skin pigmentation enhancers, J Photochem Photobio B, 2001, 63 (1-3): 148-161.
[18] Hitzel S, Driller H J, Cosmetic formulation comprising dihydroxyacetone, US patent, WO03/011240, 2003-02-13.
[19] Darmstadt T M, Langen C C, Darmstadt S H, et al., Composition containing a dihydroxyacetone precursor, US patent, 20060045856A1, 2006-03-02.
[20] Johnstone B J, Klasing K C, Calvert C C, et al., Effect of alcohol and pyruvate/dihydroxyacetone on liver and serum lipids of SCWL pullets, Nutrition Research, 1989, 9 (4): 415-421.
[21] Carmona A, Freedland R A, Effect of glycerol and dihydroxyacetone on hepatic lipogenesis, Archives of Biochemistry and Biophysics, 1989, 271 (1): 130-138.
[22] Fesq H, Brockow K, Strom K, et al., Dihydroxyacetone in a new formulation-A powerful therapeutic option in vitiligo, Dermatology, 2001, 203 (3): 241-243.
[23] Stanley B. Levy, Dihydroxyacetone-containing sunless or self-tanning lotions Journal of the American Academy of Dermatology, 1992, 27 (6): 989-993.
[24] H. Fesq, K. Boeck, K. Brockow, et al., Dihydroxyacetone (Autohélios?): a powerful therapeutical option in vitiligo, Journal of the European Academy of Dermatology and Venereology, 1998, 11 (2): s183-s184.
[25] Hsu L Y, Wise D S, Kucera L S, et al., Regioselective synthesis of .DELTA.6-, .DELTA.7-, and .DELTA.8-14.alpha.-cyanosterol derivatives: versatile precursors to 14.alpha.-demethylase inhibitors, J. Org. Chem., 1992, 57 (12): 3354-3358.
[26] Comber R N, Reynolds R C, Friedrich J D, et al., 5,5-Disubstituted hydantoins:syntheses and anti-HIV activity, J. Med. Chem., 1992, 35 (19): 3567-3572.
[27] Stanko, R T, Adibi S A, Inhibition of lipid accumulation and enhancement of energy expenditure by the addition of pyruvatee and dihydroxyacetone to a rat diet, Metabolism, 1986, 35: 182-186.
[28] Stanko R T, Arch J E, Inhibition of regain in body weight and fat with addition of 3 carbon compounds to the diet with hyper energe ticre feeding after weight reduction, Int Jobes. Relat. Metab. Disorders, 1996, 20: 925-930.
[29]张精安,丙酮醛的合成与应用,香料香精化妆品,1992,264 (3): 3-6.
[30]郑裕国,胡忠策,柳志强,沈寅初,微生物法生产二羟基丙酮,中国专利,CN1821418A,2006-08-23.
[31] Ciriminna R, Palmisano G, Pina C D, et al., One-pot electrocatalytic oxidation of glycerol to DHA. Tetrahedron Lett., 2006, 47: 6993-6995.
[32] Demirel S, Lehnert K, Lucas M, et al., Use of renewable for the production of chemicals: Glycerol oxidation over carbon supported gold catalysts, Applied Catalysis B: Environmental, 2007, 70 (1-4): 637-643.
[33]陆新德,甲基咪唑生产技术及市场需求,精细石油化工,1999,4:58~60
[34] Bories A, Claret C, Soueaille P. Kinetic study and optimization of the production of dihydroxyacetone from glycerol using Gluconobacter oxydans, Proc. Biochem., 1991, 26: 243-248.
[35]姚日生,金友华,一氯丙酮酯化醇解法制备羟基丙酮,湖南化工,2000,6 (30): 32-33.
[36] Hauge J G, King T E, Cheldelin V H, Alternate conversions of glycerol to dihydroxyacetone in Acetobacter suboxydans, J. Biol. Chem., 1954, 203: 1-9.
[37] Blazejak S, Sobcjak E, Bioconversion of glycerol into dihydroxyacetone DHA using Acetobacter xylinum, Acta Aliment Pol., 1988, 14: 207-216.
[38] Holst O, Lundback M, Mattiasson B, Hydrogen peroxide as an oxygen source for immobilized Gluconobacter oxydans converting glycerol to dihydroxyacetone, Appl. Microbiol. Biotechnol., 1985, 22: 383-388.
[39] Pomortseva N V, Krasil'Nikov T N, Paleeva M, et al., Production of dihydroxyacetone by a suspension of resting Acetobacter suboxydans cells. J. Appl. Biochem. Microbiol., 1981, 10: 46-49.
[40] Nabe K, Nobuhiko I, Shigeki Y, et al., Conversion of Glycerol to Dihydroxyacetone by Immobilized Whole Cells of Acetobacter xylinum, Applied and Environmental Microbiology, 1979, 38 (6): 1056-1060.
[41] Wei S, Song Q, Wei D, Production of Gluconobacter oxydans cells from low-cost culture medium for conversion of glycerol to dihydroxyacetone, Prep. Biochem. Biotechnol., 2007, 37 (1): 67-76.
[42] Subedi K P, Kim I, Kim J, et al., Role of GldA in dihydroxyacetone and methylglyoxal metabolism of Escherichia coli K12, FEMS Microbiol. Lett., 2008, 279 (2): 180-187.
[43] van der Klei I J, van der Heide M, Baerends R J, et al., The Hansenula polymorpha per6 mutant is affected in two adjacent genes which encode dihydroxyacetone kinase and a novel protein, Pak1p, involved in peroxisome integrity, Curr. Genet., 1998, 34 (1): 1-11.
[44] Ruch F E Jr, Lin E C, Kowit J D, et al., In vivo inactivation of glycerol dehydrogenase in Klebsiella aerogenes: properties of active and inactivated proteins, J. Bacteriol., 1980, 141 (3): 1077-1085.
[45] Pyle J E, Howe H B Jr, Uptake and dissimilation of glycerol by wild type and glycerol nonutilizing strains of Neurospora crassa, Mol. Gen. Genet., 1983, 189 (1): 166-168.
[46] Liu Z Q, Hu Z C, Zheng Y G, Optimization of Cultivation Conditions for the Production of 1,3-Dihydroxyacetone by Pichia membranifaciens Using Response Surface Methodology, Biochemical Engineering Journal, 2008, 38 (3): 285-291.
[47] Morgunov I G, Ilchenko A P, Isolation, purification, and some properties of glycerol dehydrogenase from the yeast Candida valida, Biochem-Moscow, 1995, 60 (6): 883-890.
[48] Flickinger M C, Perlman D. Application of oxygen-enriched aeration in the conversion of glycerol to dihydroxyacetone by Gluconobacter melanogenus IFO 3293. Appl. Environ. Microbiol., 1977, 33 (3): 706-712.
[49]章朝辉,胡忠策,郑裕国,生物转化生产二羟基丙酮的研究进展,化学与生物工程,2007,24 (1): 1-3.
[50] Magasanik B, Brooke M S, Karibian D. Metabolic pathways of glycerol dissimilation, J. Bacteriol., 1953, 66 (5): 611-619.
[51] Ohrem H L, Vo? H, Process Model of the Oxidation of Glycerol with Gluconobacter oxydans, Proc. Biochem., 1996, 31 (3): 295-301.
[52] Prust C, Hoffmeister M, Liesegang H, et al., Complete genome sequence of the acetic acid bacterium Gluconobacter oxydans, Nature Biotecnology, 2005, 23 (2): 195-200.
[53] Rutten A M G, Biochemical production of dihydroxyacetone from glycerol, Resueil, 1951, 70: 449-456.
[54] Yamada S, Nabe K, Izuo N, et al., Fermentative production of dihydroxyacetone by Acetobacter suboxydans ATCC 621, J Ferment Technol, 1979, 57 (3): 215~220
[55] Meybeek A, A spectroscopic study of the reaction products of dihydroxyacetone with aminoacids, J. Soc. Cosmet. Chem., 1977, 28, 25-28.
[56]张嗣良,李凡超,发酵过程中pH及溶解氧的测量与控制,上海:华东化工学院出版社, 1992, 90-91.
[57] Yamada S, Wada M, Chibata I, Effect of high oxygen partial pressure on the conversion of sorbitol to sorbose by Acetobacter suboxydans, J. Ferment. Technol., 1978, 56: 29-34.
[58] Hekmat D, Bauer R, Fricke J, Optimization of the microbial synthesis of dihydroxyacetone from glycerol with Gluconobactero xydans, Bioprocess Biosyst. Eng., 2003, 26: 109-116.
[59] Bauer R, Katsikis N, Varga S, et al., Study of the inhibitory effect of the product dihydroxyacetone on Gluconobacter oxydans in a semi-continuous two-stage repeated-fed-batch process, Bioproc. Biosyst. Eng. 2005, 5: 37-43.
[60] Hekmat D, Bauer R, Neff V, Optimization of the microbial synthesis of dihydroxyacetone in a semi-continuous repeated-fed-batch process by in situ immobilization of Gluconobacter oxydans, Proc. Biochem., 2007, 42: 71-76.
[61] Mishra R, Jain S R, Kumar A, Microbial production of dihydroxyacetone, Biotechnology Advances, 2008, 26 (4): 293-303.
[62] Adlercreutz P, Hoist O, Mattiasson B, Characterization of Gluconobacter oxydans immobilized in calcium alginate, Appl. Microbiol. Biot., 1985, 22: 1-7.
[63] Wei S H, Song Q X, Wei D Z, Repeated use of immobilized Gluconobacter oxydans cells for conversion of glycerol to dihydroxyacetone. Prep. Biochem. Biotech., 2007a, 37: 67-76.
[64]冯屏,周家春,严希康等,弱氧化醋酸杆菌静止细胞氧化活性的研究及1,3-二羟基丙酮的制备。食品与发酵工业,2005,31 (6): 22-26.
[65] Izuo N, Nabe K, Yamada S, et al., Production of dihydroxyacetone by continuous cultivation of Acetobacter suboxydan. J. Ferment. Technol., 1980, 58 (3): 221-226.
[66] Claret C, Bories A, Soucaille P, Glycerol Inhibition of Growth and Dihydroxyacetone Production by Gluconobacter oxydans, Current Microbiology, 1992, 25: 149-155.
[67]岑沛霖等,工业微生物学,北京:化学工业出版社,2000,116-117.
[68]张霞,微生物转化法生产二羟基丙酮,[硕士学位论文],杭州,浙江工业大学,2001.
[69] Lin E C C, Magasanik B, The Activation of glycerol dehydrogenase from Aerobacter aerogenes by Monovalent Cations, Journal of Biological Chemistry, 1960, 235 (6): 1820-1823.
[70] Johnson E A, Levine R L, Lin E C C, Inactivation of Glycerol Dehydrogenase of Klebsiella pneumoniae and the Role of Divalent Cations, Journal of Bacteriology, 1985, 164 (1): 479-483.
[71] Wethmar M, Deckwer W D, Semisynthetic culture medium for growth and dihydroxyacetone production by Gluconobacter oxydans, Biotechnology Techniques, 1999, 13: 283-287.
[72] Batzing B L, Claus G W, Biphasic Growth of Acetobacter suboxydans on a Glycerol-limiting Medium, Journal of Bacteriology, 1971, 108 (1): 592-595.
[73] Yamada S, Nabe K, Izuo N, et al., Enzymatic Production of Dihydroxyacetone by Acetobacter suboxydans ATCC 621, J. Ferment. Technol., 57 (5): 221-226.
[74]冯屏,周家春,徐玉佩等,膜生物反应器连续发酵法制取二羟基丙酮的研究,食品与发酵工业,2003,29 (12): 40-43.
[75] William C, Process for the production of dihydroxyacetone, US patent, 577041, 1975-7-17.
[76]郑裕国,胡忠策,柳志强,等,微生物法生产二羟基丙酮,中国专利,CN 1821418A,2005-12-13.
[77]张小飞,氧化葡萄酸杆菌转化甘油生产二羟基丙酮的研究,[硕士学位论文],重庆,西南交通大学,2006.
[78]鲁诗锋,发酵液中1,3-丙二醇的分离提取工艺的研究,[硕士学位论文],大连,大连理工大学,2006.
[79] Chen X, Zhang D J, Qi W T, et al., Microbial Fed-batch Production of 1,3-Propanediol by Klebsiella pneumoniae under Micro-aerobic conditions, App. Microbial. Biotechnol., 2003, 63: 143-146.
[80]刘国诠等,生物工程下游技术,北京:化学工业出版社,2003,96-103.
[81]章名春,工业微生物诱变育种,北京:科学出版社,1984.
[82] G?tgens C, Degner U, Bringer-Meyer S, et al., Biotransformation of glycerol to dihydroxyacetone by recombinant Gluconobacter oxydans DSM2343, Appl. Microbiol. Biotechnol., 2007, 76 (3):553-559.
[83] Acuna A K, Englande Jr A J, Hu C, et al., Methyl tertiary-butyl ether (MTBE)biodegradation in batch and continuous upflow fixed-biofilm reactors, Water Sci. Technol., 2000, 42 (5~6): 153-161.
[84] Aksu Z, Akp?nar D, Modelling of simultaneous biosorption of phenol and nickel (II) onto dried aerobic activated sludge, Sep. Purif. Technol., 2000, 21 (1~2): 87-99.
[85] Mester L, Szabados L, Differences constitutionneles et fonctionnelles les fragments glacidiques du fibrinogene humain normal et d’un fibrinogene humaine anormal, Bull. Soc. Chim. Biol., 1968, 50: 2561-2566.
[86]姜岩,Candida tropicalis激光育种技术及其降酚特性研究,[博士学位论文],天津;天津大学,2005.
[87] Kishioka S, Tamura K, Miyashita M, Biological stimulation of low-power He-Ne laser on yeast under high pressure, Progress in Biotechnology, 1996, 13: 113-116.
[88] Kohli R, Biplab B, Kumar G P, Induction of phr gene expression in E. coli strain KY706/pPL-1 by He–Ne laser (632.8 nm) irradiation, J. Photochem. Photobiol. B: Biol., 2001, 60 (2-3): 136-142.
[89] Lu W Y, Wen J P, Jia X Q, et al., Effect of He-Ne laser irradiation on hydrogen production by Enterobacter aerogenes, International Journal of Hydrogen Energy, 2008, 33: 34-42.
[90] Jiang Y, Wen J P, Caiyin Q G L, et al., Mutation of He-Ne Laser Irradiation on Candida Tropicalis for Phenol Biodegradation, Chemosphere, 2006, 65: 1236-1241.
[91]卢文玉,闻建平,范晶华等,激光诱变玫瑰孢链霉菌结合链霉素抗性筛选法选育达托霉素高产菌株,微生物学通报,33(3): 114-117.
[92]李耀维,冯文新,张素梅,He-Ne激光对金针菇SOD高产株的诱变效应,激光生物学报,2002,11(4): 283-286.
[93] Li H M, Huang R Q, The screening of baker’s yeast by laser irradiation, Acta Photonica Sinica, 2001, 30: 1381-1383.
[94] Logan I D, McKenna P G, Barnett Y A, An investigation of the cytotoxic and mutagenic potential of low intensity laser irradiation in Friend erythroleukaemia cells. Mutation res., 1995, 347: 67-71.
[95] Kohli R, Pradeep K G, Irradiance dependence of the He–Ne laser-induced protection against UVC radiation in E. coli strains, J. Photochem. Photobiol. B: Biol., 2003, 69: 161-167.
[96] Karu T, Tiphlova O, Esenaliev R, et al., Two different mechanisms of low-intensity laser photobiological effects on Escherichia colii. J. Photochem. Photobiol. B: Biol., 1994, 24: 155-161.
[97] Ulla G P, Bernd S, Rainer H, Laser pyrolysis products—genotoxic, clastogenic and mutagenic effects of the particulate aerosol fractions, Mutation Res., 1999, 441: 29-41.
[98] Repice F, Zonefrati R, Irradiation at low energy levels with laser and incoherent infrared sources on rat osteoblasts cultured in vitro, Arch. Ital. Anat. Embr., 1987, 92: 299-304.
[99] Funk J O, Kruse A, Kirchner H, Cytokine production after helium-neon laser irradiation in cultures of human peripheral blood mononuclear cells, J. Photochem. Photobiol. B: Biol., 1992, 16: 347~355
[100] Lubart R, Friedmann H, Lavie T, et al., Effect of light on calcium transport in bull sperm cells, J. Photochem. Photobiol. B: Biol., 1992, 15: 337~341
[101]杜连祥等,工业微生物学试验技术,天津:天津科学技术出版社,1999.
[102]王剑锋,修志龙,范圣第,甘油转化生产1 ,3-丙二醇发酵液中甘油含量的测定,工业微生物,2001,31(2): 33-35.
[103] Chen X C, Bai J X, Cao J M, et al., Medium optimization for the production of cyclic adenosine 3′,5′-monophosphate by Microbacterium sp. no. 205 using response surface methodology, Bioresource Technology, 2009, 100 (2): 710-716.
[104] Pan H F, Xie Z P, Bao W N, et al., Optimization of culture conditions to enhance cis-epoxysuccinate hydrolase production in Escherichia coli by response surface methodology, Biochemical Engineering Journal, 2008, 42 (2): 133-138.
[105] Deepak V, Kalishwaralal K, Ramkumarpandian S, et al., Optimization of media composition for Nattokinase production by Bacillus subtilis using response surface methodology, Bioresource Technology, 2008, 99 (17): 8170-8174.
[106] Rajendran A, Palanisamy A, Thangavelu V, Evaluation of Medium Components by Plackett-Burman Statistical Design for Lipase Production by Candida rugosa and Kinetic Modeling, Chinese Journal of Biotechnology, 2008, 24 (3): 436-444.
[107] Chang M Y, Tsai G J, Houng J Y, Optimization of the medium composition for the submerged culture of Ganoderma lucidum by Taguchi array design and steepest ascent method, Enzyme and Microbial Technology, 2006, 38 (3-4): 407-414.
[108] Chang C F, Wong J J, Chiou J P, et al., Robust searching hybrid differential evolution method for optimal reactive power planning in large-scale distribution systems, Electric Power Systems Research, 2007, 77 (5-6): 430-437.
[109] Yamamoto H, Yamaji H, Fukusaki E, Canonical correlation analysis for multivariate regression and its application to metabolic fingerprinting, BiochemicalEngineering Journal, 2008, 40 (2): 199-204.
[110] Kim J S, Kwon O J, Assessment of implicit operators for the upwind point Gauss–Seidel method on unstructured meshes, Computers & Fluids, 2007, 36 (8): 1335-1346.
[111] Sacco W F, Filho H A, Henderson N, et al., A Metropolis algorithm combined with Nelder–Mead Simplex applied to nuclear reactor core design, Annals of Nuclear Energy, 2008, 35 (5): 861-867.
[112] Plackett R L, Burman J P, The design of optimum multifactorial experiments, Biometrika, 1946, 33: 305-325.
[113] Chauhan K, Trivedi U, Patel K C, Statistical screening of medium components by Plackett–Burman design for lactic acid production by Lactobacillus sp. KCP01 using date juice, Bioresource Technology, 2007, 98 (1): 98-103.
[114] Naveena B J, Altaf M, Bhadriah K, et al., Selection of medium components by Plackett–Burman design for production of (+) lactic acid by Lactobacillus amylophilus GV6 in SSF using wheat bran, Bioresource Technology, 2005, 96 (4): 485-490.
[115] Levin L, Forchiassin F, Viale A, Ligninolytic enzyme production and dye decolorization by Trametes trogii: application of the Plackett–Burman experimental design to evaluate nutritional requirements, Process Biochemistry, 2005, 40 (3-4): 1381-1387.
[116] Ahuja S K, Ferreira G M, Moreira A R, Application of Plackett-Burman design and response surface methodology to achieve exponential growth for aggregated shipworm bacterium, Biotechnology and Bioengineering, 2004, 85 (6): 666-675.
[117]陈宁,常高峰,张克旭,L-异亮氨酸发酵培养基的响应面法优化,食品与发酵工业,2004,30 (2): 33-37.
[118] Liu Z Q, Hu Z C, Zheng Y G, et al., Optimization of Cultivation Conditions for the Production of 1,3-Dihydroxyacetone by Pichia membranifaciens Using Response Surface Methodology, Biochemical Engineering Journal, 2008, 38 (3): 285-291.
[119] Bund R K, Pandit A B, Rapid lactose recovery from paneer whey using sonocrystallization: A process optimization, Chemical Engineering and Processing, 2007, 46 (9): 846-850.
[120] Johnson P E, Elementary Statistics with Minitab, Teaching Statistics, 1991, 13 (2): 40-42.
[121] Tania Prvan, Anna Reid, Peter Petocz, Statistical Laboratories Using Minitab,SPSS and Excel: A Practical Comparison, Teaching Statistics, 2002, 24 (2): 68-75.
[122] Claret C, Bories A, Soucaille P, Glycerol Inhibition of Growth and Dihydroxyacetone Production by Gluconobacter oxydans, Current Microbiology, 1992, 25: 149-155.
[123] Claret C, Bories A, Soucaille P, Inhibitory effect of dihydroxyacetone on Gluconobacter oxydans: Kinetic aspects and expression by mathematical equations, Journal of Industrial Microbiology, 1993, 11: 105-112.
[124] Bauer R, Hekmat D, Development of a Transient Segregated Mathematical Model of the Semicontinuous Microbial Production Process of Dihydroxyacetone, Biotechnol Prog, 2006, 22: 278-284.
[125] Y Zhu, Youssef D, Porte C, et al., Study of the solubility and the metastable zone of 1,3-dihydroxyacetone for the drowning-out process, Journal of Crystal Growth, 2003, 257: 370-377.
[126]孟令芝等,有机波谱分析,武汉:武汉大学出版社,2003.
[2]李尧,微生物发酵生产二羟基丙酮的应用研究进展,四川食品与发酵,2007,43 (139): 20-23.
[3] Sommer K, Bohlmann U, Bohnet M, Production of Dihydroxyacetone in a Three Phase Fluidized Bed Reactor Using Gluconobacter Oxydans, Chem. Eng. Technol., 1998, 21(2): 144-149.
[4] Bicker M, Endres S, Ott L, Vogel H, Catalytical conversion of carbohydrates in subcritical water: A new chemical process for lactic acid production, J. Mol. Catal. A-Chem., 2005, 239 (1-2): 151-157.
[5] Murga J, Falomir E, Carda M, et al., Chlorodicyclohexylborane-Mediated Aldol Additions ofα,α‘-Dioxygenated Ketones, Org. Lett. 2001, 3 (6): 901-904.
[6] Kim K S, Hong S D, Synthesis and stereoselective aldol reaction of dihydroxyacetone derivatives, Tetrahedron Lett. 2000, 41 (31): 5909-5913.
[7] Enders D, Voith M, Lenzen A, The Dihydroxyacetone Unit—A Versatile C3 Building Block in Organic Synthesis, Angew. Chem. Int. Ed., 2005, 44: 1304-1325.
[8] Tamura Y, Yakura T, Haruta J I, An efficient conversion of keto groups into dihydroxyacetone groups: Oxidation of ethynylcarbinol intermediates by using hypervalent iodine reagent, Tetrahedron Letters, 1985, 26 (32): 3837-3840.
[9] Schmincke H, Hoppe D, Studies toward the total synthesis of 1-oxacephalosporins 3: synthesis of a (±)-trans-7-benzoylamino-3-carbamoyloxymethyl-1-oxa-3-cepheh -3-carboxylate from 1,3-dihydroxyacetone, Tetrahedron, 1989, 45 (3): 701-707.
[10] Waagen V, Partali V, Hollingster I, et al., Dihydroxyacetone dimers; solution and crystal structure of stereoisomers of 2,5-diethoxy-1,4-dioxane-2,5-dimethanol, Tetrahedron, 1994, 50 (33): 10055-10060.
[11] Araki Y, Nagasawa J I, Ishido Y, Synthetic studies of carbohydrate derivatives by photochemical reactions. Part 16. Synthesis of DL-apiose derivatives by photochemical cycloaddition of 1,3-dihydroxypropan-2-one derivatives with ethenediol or ethenol derivatives, J. Chem. Soc. Perkin Trans. 1, 1981, 12-23.
[12] Olsen R K, Feng X, Campbell M, et al., Synthesis of Functionalized Aryloxy 1,3-Butadienes and Their Transformation to Diaryl Ethers via Diels-Alder Cycloaddition Reactions, J. Org. Chem. 1995, 60 (19): 6025-6031.
[13] Walker L F, Connolly S, Wills M, Synthesis of 2,5-dihydrofurans via alkylidene carbene insertion reactions, Tetrahedron Lett. 1998, 39 (29): 5273-5276.
[14] Shimada S, Hashimoto Y, Nagashima T, et al., Diastereoselective ring-opening aldol-type reaction of 2,2-dialkoxycyclopropanecarboxylic esters with carbonyl compounds. 2. Synthesis of cis-2,3-substituted-γ-lactones, Tetrahedron 1993, 49 (8): 1589-1604.
[15] Fujiwara K, Amano A, Tokiwano T, Novel Oxepane Formation by TiCl4-Catalyzed Nucleophilic Cleavage of 1-Alkoxymethyl-6,8-dioxabicyclo [3.2.1] octanes, Tetrahedron 2000, 56 (8): 1065-1080.
[16]汪连生,程巳雪,卓仁禧,从二羟基丙酮出发合成新型聚碳酸酯[EB/OL], http://www.polymer.cn,2004-11-14.
[17] Brown D A, Skin pigmentation enhancers, J Photochem Photobio B, 2001, 63 (1-3): 148-161.
[18] Hitzel S, Driller H J, Cosmetic formulation comprising dihydroxyacetone, US patent, WO03/011240, 2003-02-13.
[19] Darmstadt T M, Langen C C, Darmstadt S H, et al., Composition containing a dihydroxyacetone precursor, US patent, 20060045856A1, 2006-03-02.
[20] Johnstone B J, Klasing K C, Calvert C C, et al., Effect of alcohol and pyruvate/dihydroxyacetone on liver and serum lipids of SCWL pullets, Nutrition Research, 1989, 9 (4): 415-421.
[21] Carmona A, Freedland R A, Effect of glycerol and dihydroxyacetone on hepatic lipogenesis, Archives of Biochemistry and Biophysics, 1989, 271 (1): 130-138.
[22] Fesq H, Brockow K, Strom K, et al., Dihydroxyacetone in a new formulation-A powerful therapeutic option in vitiligo, Dermatology, 2001, 203 (3): 241-243.
[23] Stanley B. Levy, Dihydroxyacetone-containing sunless or self-tanning lotions Journal of the American Academy of Dermatology, 1992, 27 (6): 989-993.
[24] H. Fesq, K. Boeck, K. Brockow, et al., Dihydroxyacetone (Autohélios?): a powerful therapeutical option in vitiligo, Journal of the European Academy of Dermatology and Venereology, 1998, 11 (2): s183-s184.
[25] Hsu L Y, Wise D S, Kucera L S, et al., Regioselective synthesis of .DELTA.6-, .DELTA.7-, and .DELTA.8-14.alpha.-cyanosterol derivatives: versatile precursors to 14.alpha.-demethylase inhibitors, J. Org. Chem., 1992, 57 (12): 3354-3358.
[26] Comber R N, Reynolds R C, Friedrich J D, et al., 5,5-Disubstituted hydantoins:syntheses and anti-HIV activity, J. Med. Chem., 1992, 35 (19): 3567-3572.
[27] Stanko, R T, Adibi S A, Inhibition of lipid accumulation and enhancement of energy expenditure by the addition of pyruvatee and dihydroxyacetone to a rat diet, Metabolism, 1986, 35: 182-186.
[28] Stanko R T, Arch J E, Inhibition of regain in body weight and fat with addition of 3 carbon compounds to the diet with hyper energe ticre feeding after weight reduction, Int Jobes. Relat. Metab. Disorders, 1996, 20: 925-930.
[29]张精安,丙酮醛的合成与应用,香料香精化妆品,1992,264 (3): 3-6.
[30]郑裕国,胡忠策,柳志强,沈寅初,微生物法生产二羟基丙酮,中国专利,CN1821418A,2006-08-23.
[31] Ciriminna R, Palmisano G, Pina C D, et al., One-pot electrocatalytic oxidation of glycerol to DHA. Tetrahedron Lett., 2006, 47: 6993-6995.
[32] Demirel S, Lehnert K, Lucas M, et al., Use of renewable for the production of chemicals: Glycerol oxidation over carbon supported gold catalysts, Applied Catalysis B: Environmental, 2007, 70 (1-4): 637-643.
[33]陆新德,甲基咪唑生产技术及市场需求,精细石油化工,1999,4:58~60
[34] Bories A, Claret C, Soueaille P. Kinetic study and optimization of the production of dihydroxyacetone from glycerol using Gluconobacter oxydans, Proc. Biochem., 1991, 26: 243-248.
[35]姚日生,金友华,一氯丙酮酯化醇解法制备羟基丙酮,湖南化工,2000,6 (30): 32-33.
[36] Hauge J G, King T E, Cheldelin V H, Alternate conversions of glycerol to dihydroxyacetone in Acetobacter suboxydans, J. Biol. Chem., 1954, 203: 1-9.
[37] Blazejak S, Sobcjak E, Bioconversion of glycerol into dihydroxyacetone DHA using Acetobacter xylinum, Acta Aliment Pol., 1988, 14: 207-216.
[38] Holst O, Lundback M, Mattiasson B, Hydrogen peroxide as an oxygen source for immobilized Gluconobacter oxydans converting glycerol to dihydroxyacetone, Appl. Microbiol. Biotechnol., 1985, 22: 383-388.
[39] Pomortseva N V, Krasil'Nikov T N, Paleeva M, et al., Production of dihydroxyacetone by a suspension of resting Acetobacter suboxydans cells. J. Appl. Biochem. Microbiol., 1981, 10: 46-49.
[40] Nabe K, Nobuhiko I, Shigeki Y, et al., Conversion of Glycerol to Dihydroxyacetone by Immobilized Whole Cells of Acetobacter xylinum, Applied and Environmental Microbiology, 1979, 38 (6): 1056-1060.
[41] Wei S, Song Q, Wei D, Production of Gluconobacter oxydans cells from low-cost culture medium for conversion of glycerol to dihydroxyacetone, Prep. Biochem. Biotechnol., 2007, 37 (1): 67-76.
[42] Subedi K P, Kim I, Kim J, et al., Role of GldA in dihydroxyacetone and methylglyoxal metabolism of Escherichia coli K12, FEMS Microbiol. Lett., 2008, 279 (2): 180-187.
[43] van der Klei I J, van der Heide M, Baerends R J, et al., The Hansenula polymorpha per6 mutant is affected in two adjacent genes which encode dihydroxyacetone kinase and a novel protein, Pak1p, involved in peroxisome integrity, Curr. Genet., 1998, 34 (1): 1-11.
[44] Ruch F E Jr, Lin E C, Kowit J D, et al., In vivo inactivation of glycerol dehydrogenase in Klebsiella aerogenes: properties of active and inactivated proteins, J. Bacteriol., 1980, 141 (3): 1077-1085.
[45] Pyle J E, Howe H B Jr, Uptake and dissimilation of glycerol by wild type and glycerol nonutilizing strains of Neurospora crassa, Mol. Gen. Genet., 1983, 189 (1): 166-168.
[46] Liu Z Q, Hu Z C, Zheng Y G, Optimization of Cultivation Conditions for the Production of 1,3-Dihydroxyacetone by Pichia membranifaciens Using Response Surface Methodology, Biochemical Engineering Journal, 2008, 38 (3): 285-291.
[47] Morgunov I G, Ilchenko A P, Isolation, purification, and some properties of glycerol dehydrogenase from the yeast Candida valida, Biochem-Moscow, 1995, 60 (6): 883-890.
[48] Flickinger M C, Perlman D. Application of oxygen-enriched aeration in the conversion of glycerol to dihydroxyacetone by Gluconobacter melanogenus IFO 3293. Appl. Environ. Microbiol., 1977, 33 (3): 706-712.
[49]章朝辉,胡忠策,郑裕国,生物转化生产二羟基丙酮的研究进展,化学与生物工程,2007,24 (1): 1-3.
[50] Magasanik B, Brooke M S, Karibian D. Metabolic pathways of glycerol dissimilation, J. Bacteriol., 1953, 66 (5): 611-619.
[51] Ohrem H L, Vo? H, Process Model of the Oxidation of Glycerol with Gluconobacter oxydans, Proc. Biochem., 1996, 31 (3): 295-301.
[52] Prust C, Hoffmeister M, Liesegang H, et al., Complete genome sequence of the acetic acid bacterium Gluconobacter oxydans, Nature Biotecnology, 2005, 23 (2): 195-200.
[53] Rutten A M G, Biochemical production of dihydroxyacetone from glycerol, Resueil, 1951, 70: 449-456.
[54] Yamada S, Nabe K, Izuo N, et al., Fermentative production of dihydroxyacetone by Acetobacter suboxydans ATCC 621, J Ferment Technol, 1979, 57 (3): 215~220
[55] Meybeek A, A spectroscopic study of the reaction products of dihydroxyacetone with aminoacids, J. Soc. Cosmet. Chem., 1977, 28, 25-28.
[56]张嗣良,李凡超,发酵过程中pH及溶解氧的测量与控制,上海:华东化工学院出版社, 1992, 90-91.
[57] Yamada S, Wada M, Chibata I, Effect of high oxygen partial pressure on the conversion of sorbitol to sorbose by Acetobacter suboxydans, J. Ferment. Technol., 1978, 56: 29-34.
[58] Hekmat D, Bauer R, Fricke J, Optimization of the microbial synthesis of dihydroxyacetone from glycerol with Gluconobactero xydans, Bioprocess Biosyst. Eng., 2003, 26: 109-116.
[59] Bauer R, Katsikis N, Varga S, et al., Study of the inhibitory effect of the product dihydroxyacetone on Gluconobacter oxydans in a semi-continuous two-stage repeated-fed-batch process, Bioproc. Biosyst. Eng. 2005, 5: 37-43.
[60] Hekmat D, Bauer R, Neff V, Optimization of the microbial synthesis of dihydroxyacetone in a semi-continuous repeated-fed-batch process by in situ immobilization of Gluconobacter oxydans, Proc. Biochem., 2007, 42: 71-76.
[61] Mishra R, Jain S R, Kumar A, Microbial production of dihydroxyacetone, Biotechnology Advances, 2008, 26 (4): 293-303.
[62] Adlercreutz P, Hoist O, Mattiasson B, Characterization of Gluconobacter oxydans immobilized in calcium alginate, Appl. Microbiol. Biot., 1985, 22: 1-7.
[63] Wei S H, Song Q X, Wei D Z, Repeated use of immobilized Gluconobacter oxydans cells for conversion of glycerol to dihydroxyacetone. Prep. Biochem. Biotech., 2007a, 37: 67-76.
[64]冯屏,周家春,严希康等,弱氧化醋酸杆菌静止细胞氧化活性的研究及1,3-二羟基丙酮的制备。食品与发酵工业,2005,31 (6): 22-26.
[65] Izuo N, Nabe K, Yamada S, et al., Production of dihydroxyacetone by continuous cultivation of Acetobacter suboxydan. J. Ferment. Technol., 1980, 58 (3): 221-226.
[66] Claret C, Bories A, Soucaille P, Glycerol Inhibition of Growth and Dihydroxyacetone Production by Gluconobacter oxydans, Current Microbiology, 1992, 25: 149-155.
[67]岑沛霖等,工业微生物学,北京:化学工业出版社,2000,116-117.
[68]张霞,微生物转化法生产二羟基丙酮,[硕士学位论文],杭州,浙江工业大学,2001.
[69] Lin E C C, Magasanik B, The Activation of glycerol dehydrogenase from Aerobacter aerogenes by Monovalent Cations, Journal of Biological Chemistry, 1960, 235 (6): 1820-1823.
[70] Johnson E A, Levine R L, Lin E C C, Inactivation of Glycerol Dehydrogenase of Klebsiella pneumoniae and the Role of Divalent Cations, Journal of Bacteriology, 1985, 164 (1): 479-483.
[71] Wethmar M, Deckwer W D, Semisynthetic culture medium for growth and dihydroxyacetone production by Gluconobacter oxydans, Biotechnology Techniques, 1999, 13: 283-287.
[72] Batzing B L, Claus G W, Biphasic Growth of Acetobacter suboxydans on a Glycerol-limiting Medium, Journal of Bacteriology, 1971, 108 (1): 592-595.
[73] Yamada S, Nabe K, Izuo N, et al., Enzymatic Production of Dihydroxyacetone by Acetobacter suboxydans ATCC 621, J. Ferment. Technol., 57 (5): 221-226.
[74]冯屏,周家春,徐玉佩等,膜生物反应器连续发酵法制取二羟基丙酮的研究,食品与发酵工业,2003,29 (12): 40-43.
[75] William C, Process for the production of dihydroxyacetone, US patent, 577041, 1975-7-17.
[76]郑裕国,胡忠策,柳志强,等,微生物法生产二羟基丙酮,中国专利,CN 1821418A,2005-12-13.
[77]张小飞,氧化葡萄酸杆菌转化甘油生产二羟基丙酮的研究,[硕士学位论文],重庆,西南交通大学,2006.
[78]鲁诗锋,发酵液中1,3-丙二醇的分离提取工艺的研究,[硕士学位论文],大连,大连理工大学,2006.
[79] Chen X, Zhang D J, Qi W T, et al., Microbial Fed-batch Production of 1,3-Propanediol by Klebsiella pneumoniae under Micro-aerobic conditions, App. Microbial. Biotechnol., 2003, 63: 143-146.
[80]刘国诠等,生物工程下游技术,北京:化学工业出版社,2003,96-103.
[81]章名春,工业微生物诱变育种,北京:科学出版社,1984.
[82] G?tgens C, Degner U, Bringer-Meyer S, et al., Biotransformation of glycerol to dihydroxyacetone by recombinant Gluconobacter oxydans DSM2343, Appl. Microbiol. Biotechnol., 2007, 76 (3):553-559.
[83] Acuna A K, Englande Jr A J, Hu C, et al., Methyl tertiary-butyl ether (MTBE)biodegradation in batch and continuous upflow fixed-biofilm reactors, Water Sci. Technol., 2000, 42 (5~6): 153-161.
[84] Aksu Z, Akp?nar D, Modelling of simultaneous biosorption of phenol and nickel (II) onto dried aerobic activated sludge, Sep. Purif. Technol., 2000, 21 (1~2): 87-99.
[85] Mester L, Szabados L, Differences constitutionneles et fonctionnelles les fragments glacidiques du fibrinogene humain normal et d’un fibrinogene humaine anormal, Bull. Soc. Chim. Biol., 1968, 50: 2561-2566.
[86]姜岩,Candida tropicalis激光育种技术及其降酚特性研究,[博士学位论文],天津;天津大学,2005.
[87] Kishioka S, Tamura K, Miyashita M, Biological stimulation of low-power He-Ne laser on yeast under high pressure, Progress in Biotechnology, 1996, 13: 113-116.
[88] Kohli R, Biplab B, Kumar G P, Induction of phr gene expression in E. coli strain KY706/pPL-1 by He–Ne laser (632.8 nm) irradiation, J. Photochem. Photobiol. B: Biol., 2001, 60 (2-3): 136-142.
[89] Lu W Y, Wen J P, Jia X Q, et al., Effect of He-Ne laser irradiation on hydrogen production by Enterobacter aerogenes, International Journal of Hydrogen Energy, 2008, 33: 34-42.
[90] Jiang Y, Wen J P, Caiyin Q G L, et al., Mutation of He-Ne Laser Irradiation on Candida Tropicalis for Phenol Biodegradation, Chemosphere, 2006, 65: 1236-1241.
[91]卢文玉,闻建平,范晶华等,激光诱变玫瑰孢链霉菌结合链霉素抗性筛选法选育达托霉素高产菌株,微生物学通报,33(3): 114-117.
[92]李耀维,冯文新,张素梅,He-Ne激光对金针菇SOD高产株的诱变效应,激光生物学报,2002,11(4): 283-286.
[93] Li H M, Huang R Q, The screening of baker’s yeast by laser irradiation, Acta Photonica Sinica, 2001, 30: 1381-1383.
[94] Logan I D, McKenna P G, Barnett Y A, An investigation of the cytotoxic and mutagenic potential of low intensity laser irradiation in Friend erythroleukaemia cells. Mutation res., 1995, 347: 67-71.
[95] Kohli R, Pradeep K G, Irradiance dependence of the He–Ne laser-induced protection against UVC radiation in E. coli strains, J. Photochem. Photobiol. B: Biol., 2003, 69: 161-167.
[96] Karu T, Tiphlova O, Esenaliev R, et al., Two different mechanisms of low-intensity laser photobiological effects on Escherichia colii. J. Photochem. Photobiol. B: Biol., 1994, 24: 155-161.
[97] Ulla G P, Bernd S, Rainer H, Laser pyrolysis products—genotoxic, clastogenic and mutagenic effects of the particulate aerosol fractions, Mutation Res., 1999, 441: 29-41.
[98] Repice F, Zonefrati R, Irradiation at low energy levels with laser and incoherent infrared sources on rat osteoblasts cultured in vitro, Arch. Ital. Anat. Embr., 1987, 92: 299-304.
[99] Funk J O, Kruse A, Kirchner H, Cytokine production after helium-neon laser irradiation in cultures of human peripheral blood mononuclear cells, J. Photochem. Photobiol. B: Biol., 1992, 16: 347~355
[100] Lubart R, Friedmann H, Lavie T, et al., Effect of light on calcium transport in bull sperm cells, J. Photochem. Photobiol. B: Biol., 1992, 15: 337~341
[101]杜连祥等,工业微生物学试验技术,天津:天津科学技术出版社,1999.
[102]王剑锋,修志龙,范圣第,甘油转化生产1 ,3-丙二醇发酵液中甘油含量的测定,工业微生物,2001,31(2): 33-35.
[103] Chen X C, Bai J X, Cao J M, et al., Medium optimization for the production of cyclic adenosine 3′,5′-monophosphate by Microbacterium sp. no. 205 using response surface methodology, Bioresource Technology, 2009, 100 (2): 710-716.
[104] Pan H F, Xie Z P, Bao W N, et al., Optimization of culture conditions to enhance cis-epoxysuccinate hydrolase production in Escherichia coli by response surface methodology, Biochemical Engineering Journal, 2008, 42 (2): 133-138.
[105] Deepak V, Kalishwaralal K, Ramkumarpandian S, et al., Optimization of media composition for Nattokinase production by Bacillus subtilis using response surface methodology, Bioresource Technology, 2008, 99 (17): 8170-8174.
[106] Rajendran A, Palanisamy A, Thangavelu V, Evaluation of Medium Components by Plackett-Burman Statistical Design for Lipase Production by Candida rugosa and Kinetic Modeling, Chinese Journal of Biotechnology, 2008, 24 (3): 436-444.
[107] Chang M Y, Tsai G J, Houng J Y, Optimization of the medium composition for the submerged culture of Ganoderma lucidum by Taguchi array design and steepest ascent method, Enzyme and Microbial Technology, 2006, 38 (3-4): 407-414.
[108] Chang C F, Wong J J, Chiou J P, et al., Robust searching hybrid differential evolution method for optimal reactive power planning in large-scale distribution systems, Electric Power Systems Research, 2007, 77 (5-6): 430-437.
[109] Yamamoto H, Yamaji H, Fukusaki E, Canonical correlation analysis for multivariate regression and its application to metabolic fingerprinting, BiochemicalEngineering Journal, 2008, 40 (2): 199-204.
[110] Kim J S, Kwon O J, Assessment of implicit operators for the upwind point Gauss–Seidel method on unstructured meshes, Computers & Fluids, 2007, 36 (8): 1335-1346.
[111] Sacco W F, Filho H A, Henderson N, et al., A Metropolis algorithm combined with Nelder–Mead Simplex applied to nuclear reactor core design, Annals of Nuclear Energy, 2008, 35 (5): 861-867.
[112] Plackett R L, Burman J P, The design of optimum multifactorial experiments, Biometrika, 1946, 33: 305-325.
[113] Chauhan K, Trivedi U, Patel K C, Statistical screening of medium components by Plackett–Burman design for lactic acid production by Lactobacillus sp. KCP01 using date juice, Bioresource Technology, 2007, 98 (1): 98-103.
[114] Naveena B J, Altaf M, Bhadriah K, et al., Selection of medium components by Plackett–Burman design for production of (+) lactic acid by Lactobacillus amylophilus GV6 in SSF using wheat bran, Bioresource Technology, 2005, 96 (4): 485-490.
[115] Levin L, Forchiassin F, Viale A, Ligninolytic enzyme production and dye decolorization by Trametes trogii: application of the Plackett–Burman experimental design to evaluate nutritional requirements, Process Biochemistry, 2005, 40 (3-4): 1381-1387.
[116] Ahuja S K, Ferreira G M, Moreira A R, Application of Plackett-Burman design and response surface methodology to achieve exponential growth for aggregated shipworm bacterium, Biotechnology and Bioengineering, 2004, 85 (6): 666-675.
[117]陈宁,常高峰,张克旭,L-异亮氨酸发酵培养基的响应面法优化,食品与发酵工业,2004,30 (2): 33-37.
[118] Liu Z Q, Hu Z C, Zheng Y G, et al., Optimization of Cultivation Conditions for the Production of 1,3-Dihydroxyacetone by Pichia membranifaciens Using Response Surface Methodology, Biochemical Engineering Journal, 2008, 38 (3): 285-291.
[119] Bund R K, Pandit A B, Rapid lactose recovery from paneer whey using sonocrystallization: A process optimization, Chemical Engineering and Processing, 2007, 46 (9): 846-850.
[120] Johnson P E, Elementary Statistics with Minitab, Teaching Statistics, 1991, 13 (2): 40-42.
[121] Tania Prvan, Anna Reid, Peter Petocz, Statistical Laboratories Using Minitab,SPSS and Excel: A Practical Comparison, Teaching Statistics, 2002, 24 (2): 68-75.
[122] Claret C, Bories A, Soucaille P, Glycerol Inhibition of Growth and Dihydroxyacetone Production by Gluconobacter oxydans, Current Microbiology, 1992, 25: 149-155.
[123] Claret C, Bories A, Soucaille P, Inhibitory effect of dihydroxyacetone on Gluconobacter oxydans: Kinetic aspects and expression by mathematical equations, Journal of Industrial Microbiology, 1993, 11: 105-112.
[124] Bauer R, Hekmat D, Development of a Transient Segregated Mathematical Model of the Semicontinuous Microbial Production Process of Dihydroxyacetone, Biotechnol Prog, 2006, 22: 278-284.
[125] Y Zhu, Youssef D, Porte C, et al., Study of the solubility and the metastable zone of 1,3-dihydroxyacetone for the drowning-out process, Journal of Crystal Growth, 2003, 257: 370-377.
[126]孟令芝等,有机波谱分析,武汉:武汉大学出版社,2003.