跳到主要內容

臺灣博碩士論文加值系統

(44.200.30.73) 您好!臺灣時間:2022/08/11 03:46
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:許郁莉
研究生(外文):Yuh-Lih Hsu
論文名稱:醱酵系統操作策略之研究
論文名稱(外文):The Study of Operating Strategies in Fermentation Systems
指導教授:吳文騰
指導教授(外文):Wen-Teng Wu
學位類別:博士
校院名稱:國立清華大學
系所名稱:化學工程學系
學門:工程學門
學類:化學工程學類
論文種類:學術論文
論文出版年:2001
畢業學年度:90
語文別:中文
論文頁數:104
中文關鍵詞:醱酵程序規模放大暫態響應技術環境變數蘇力菌效應分佈圖操作策略
外文關鍵詞:fermentation processesscale uptransient response techniqueenvironmental variablesBacillus thuringiensiseffect of the environmental variableoperating strategies
相關次數:
  • 被引用被引用:0
  • 點閱點閱:173
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:1
規模放大泛指將實驗室所得之數據或資訊,轉換利用至生產用大規模反應器上之程序,其主要目的在於藉由大量生產的方式以節省時間與降低成本,提升產品競爭力。醱酵程序因有微生物的參與,在規模放大上的困難度與複雜性更高,不僅須考慮不同規模之生化反應器內流態的改變(輸送現象),同時亦須考慮時時受周遭流態影響的微生物生理代謝(動力);而後者經常成為規模放大失敗的主因,亦即傳統的規模放大策略至今仍無法有效解決之癥結所在。
本論文提出具一般性的醱酵程序規模放大新策略,可將輸送與動力兩部份同時納入考慮,並以蘇力菌的醱酵系統為例說明其應用方式。此規模放大策略包含在實驗室規模醱酵槽進行以下兩步驟:(1)建立各環境變數對目標函數之效應分佈(2D)圖;(2)韌性小的環境變數之暫態響應測試(環境變數之擾動變化)。在第1步驟中,由環境變數對目標函數之效應分佈圖顯示,若在最適操作點(目標函數的極值)附近有一平緩區域,亦即該環境變數的韌性處於可接受的某一範圍內,則規模放大時將不致造成問題,是故無須進行第2步驟的測試,僅須設法將該環境變數全程控制於該韌性範為內即可;反之則必須進行下一步測試。若在第2步驟的測試中,環境變數對各種形式的擾動均不甚敏感,亦即擾動對目標函數的影響並不顯著,則規模放大亦不成問題;反之,若擾動對目標函數會造成一定程度的影響,則可預期大規模生產的產率將會與實驗室所預期者相去甚遠。此時,吾人必須重新考慮改善製程,或在反應器內部加裝增進混合性能或氧氣質傳性能的可拆卸式設備,以避免大規模生產時發生相關問題。本論文另以蘇力菌醱酵中的一重要環境變數-pH-為例,詳細說明此規模放大策略之應用方法。首先在建立pH對目標函數-比生長速率-之效應分佈圖方面,由圖可看出在最適操作點(pH=7.15)附近並未呈現一平緩之區域,故必須進行第2步驟之變化擾動測試。此部份測試結果顯示:在對數生長期較長持續時間(50 min)的pH block pulse、與較長持續時間(5 min)的週期性pH block pulse變化,均會對最終蘇力菌素產量與菌體數目產生明顯的影響;而若在生長停滯期施加與前述類似的擾動、甚至不控制其pH值一直至醱酵終了(約24小時),對系統均無顯著影響。故於大規模生產時,尤須特別注意在對數生長期時,應避免嚴重混合不均使添加酸鹼液的控制pH動作降低產能;一旦進入生長停滯期,則可取消控制pH以降低成本。
此外,本論文同樣以蘇力菌醱酵系統為例,說明暫態響應技術若配合操作於微生物的不同生長時期,將可從中獲得該系統的適當操作策略。蘇力菌為好氣性微生物,槽內溶氧及氧氣質傳效能對其生長與生產蘇力菌素有極大的影響。就一般的機械攪拌槽而言,攪拌速率與通氣量同時決定溶氧及氧氣質傳速率,兩者均為重要的環境狀態變數;而攪拌又將造成阻礙蘇力菌生長與影響其形態的剪應力。暫態響應結果發現:在對數生長期時應設法增加系統的氧氣質傳效能;而進入生長停滯期則應設法降低蘇力菌所承受之機械剪應力,如此的操作策略將可有效提高蘇力菌素的產率約達43%。另一方面,即使利用大型攪拌槽醱酵生產蘇力菌素,亦可得到令人滿意的結果,顯示此種操作策略實對工業生產有極大的助益。

Scale-up was defined as “ The successful startup and operation of a commercial size of unit whose design and operating procedures are in part based upon experimentation and demonstration at a smaller scale of operation.” The aim of scale-up lies in saving time and lowering the cost via mass production. However, a fermentation process developed in the laboratory may not easily be scaled up to full production because it is difficult to assess certain factors affecting the scale up process. The combination of transport phenomena and kinetic behavior of microorganisms essentially governs the performance of a bioreactor. Both of these two factors are dependent on the scale of the bioreactor. As a result, many large-scale fermentation processes give a lower yield than is expected from laboratory scale experiments.
This dissertation explores a method for scaling-up a fermentation system that is based on a series of special operations in a small-scale fermentor. It consists of two parts. The first part investigates the effects of the environmental state variables on the cultivation. If a wide range of the state variables has no significant effect on yield or productivity, scaling-up is not an issue in the fermentation system. If only a small range of the state variables has no substantial impact on cultivation, pulse or periodical change of the state variables would be carried out to investigate the effects of the change on cultivation.
To illustrate the proposed method of scale-up, Bacillus thuringiensis was cultivated for thuringiensin production with the pH value as the environmental state variable. Different pH values at 7.0 and 8.4 had a significant effect on both cell growth and thuringiensin production. Variation of pH value for a short period of time did not have substantial effect on either cell growth or thuringiensin production. Therefore, if a large-scale fermentor had a short mixing time to make the variation of pH value lie within the limit, the environmental state variable, pH, did not result in the problem in the large-scale fermentor. On the contrary, when a large-scale fermentor can not provide a well-controlled condition for cultivation, design of the large-scale fermentor should be careful.
A bioprocess system with mixed-growth-associated or non-growth-associated product should have the different cultivation conditions during the cell growth stage and production stage. Cultivation of Bacillus thuringiensis for thuringiensin production is a mixed-growth-associated system. Transient response technique -- variation of agitation speed and aeration during the exponential growth phase and stationary phase respectively was applied for investigating the effect of shear stress on cultivation of B. thuringiensis for thuringiensin production. It was found that shear stress had little effect on product formation but the concentration of dissolved oxygen in the broth played a much more significant role during the exponential growth phase. However, shear stress had a substantial effect on thuringiensin production during the stationary phase. By decreasing the agitation speed during the stationary phase, the product formation could increase up to 43%. This provided an important information in cultivation of B. thuringiensis for thuringiensin production.

第一章 緒論
1-1 前言…………………………………………………………..1
1-2醱酵程序之系統操作………………………………………..2
1-2-1 生化程序之最適化……………………………………..3
1-2-2 醱酵系統之規模放大…………………………………..6
1-2-3 縮小規模與其相關應用………………………………..8
1-3生化系統的動態研究………………………………………..9
1-4生物殺蟲劑簡介……………………………………………..13
1-4-1 生物農藥之重要性……………………………………..13
1-4-2 蘇力菌桿菌與內毒素…………………………………..14
1-4-3 蘇力菌素………………………………………………..16
1-4-4 蘇力菌素之醱酵生產…………………………………..18
1-5章節組織……………………………………………………..20
第二章 實驗材料與方法
2-1菌株……………………………………………………………22
2-2 培養基………………………………………………………..22
2-3 實驗方法及操作條件………………………………………..25
2-4 實驗設備與配置……………………………………………..25
2-5 分析方法……………………………………………………..28
1. 菌體數目之測定……………………………………………28
2. 還原糖分析…………………………………………………28
3. 蘇力菌素之分析法…………………………………………29
第三章 系統操作策略在蘇力菌批式醱酵之應用
3-1 前言…………………………………………………………..31
3-2 蘇力菌醱酵培養之操作條件………………………………..32
3-3 氧氣質傳與剪應力之效應-攪拌速率與通氣量之暫態響應測試……………………………………………………….34
1. 對數生長期之block pulse 測試…………………………37
2. 生長停滯期之step change 測試………………………….42
3-4 結論………………………………………………………….47
第四章 醱酵系統規模放大之新策略
4-1前言…………………………………………………………..50
4-2 規模放大新策略……………………………………………..51
4-2-1 步驟I:環境變數對目標函數之效應…………………51
1. 重要因子篩選(Screening)……………………….51
2. 中心混成設計法(Central Composite Design)……53
3. 回應曲面之建立與ANOVA表……………………..55
4. 各環境變數對目標函數之平面圖分析…………….55
4-2-2 步驟II:環境變數之暫態響應測試…………………..56
4-3實例:以pH為環境變數探討蘇力菌醱酵系統的規模放大58
4-3-1 pH對蘇力菌比生長速率之效應……………………….58
4-3-1-1 重要因子篩選…………………………………...58
4-3-1-2 不同pH值之蘇力菌醱酵歷時走勢……………59
4-3-1-3 回應曲面及各環境變數之效應分佈圖………...63
4-3-2 pH之暫態響應測試…………………………………….67
1. 對數生長期之pH脈衝及階梯變化測試…………..67
2. 生長遲滯期之pH脈衝測試………………………..71
4-4pH的選擇與蘇力菌饋料批式醱酵………………………….77
4-4-1 蘇力菌饋料批式生產簡介……………………………..77
4-4-2 批式與饋料批式生產之操作條件比較………………..78
4-5結論…………………………………………………………..81
第五章 結論與未來展望
5-1總結…………………………………………………………..85
5-2未來展望……………………………………………………..90
參考文獻……………………………………………………………..93

Abel, C., Hübner, U., and Schügerl, K. “Transient behaviour of Baker’s yeast during enforced periodical variation of dissolved oxygen concentration.” J. Biotechnol., 32, 45-57 (1994a)
Abel, C., Linz, F., Scheper, T. and Schügerl, K. “Transient behaviour of Baker’s yeast during enforced variations of dissolved oxygen and glucose concentrations.” J. Biotechnol., 33, 183-193 (1994b)
Al-Awadhi, N., Egil, T., Hamer, G., and Mason, C. A. “The process utility of thermotolerant methylotophic bacteria: II. An evaluation in chemostat culture.” Biotechnol. Bioeng., 36, 821-825 (1990)
Allsop, P. J., Chisti, Y., Young, M., and Sullivan, G. R. “dynamics of phenol degradation by Pseudomonas putida.” Biotechnol. Bioeng., 41, 572-580 (1993)
Amanullah, A., Baba, A., McFarlane, C. M., Emery, A. N., and Nienow, A. W. “Biological Models of Mixing Performance in Bioreators.” In Nienow, A. W. (ed.) “3rd International Conference on Bioreator and Bioprocess Fluid Dynamics” Mechanical Engineering Publications, London, UK, 381-400 (1993)
Arcas, J., Yantorno, O., Arraras, E. and Ertola, R. “A new medium for growth and delta-endotoxin production by Bacillus thuringiensis var. kurstaki.” Biotechnol. Lett., 6, 495-500 (1984)
Arcas, J., Yantorno, O. and Ertola, R. “Effect of high concentration of nutrients on Bacillus thuringiensis cultures.” Biotechnol. Lett., 9, 105-110 (1987)
Bader, F. G. “Physiology and fermentation development.” In: Queener, S. W. and Day, L. E. (eds.) “The Bacteria: Antibiotic-Producing Streptomycetes” Academic Press, Orlando, 281-321 (1986)
Bartholomew, W. H., “Scale-up of Submerged Fermentation.” In Umbreit, W. W. (ed.), In Advances in Applied Microbiology, Vol. 2, 289-300 (1960)
Bond, R. P. M., Boyce, C. B. C., Rogoff, M. H., and Shieh, T. P. “The thermostable exotoxin of Bacillus thuringiensis.” In: Burges, H. D. and Hussey, N. W. (eds.), Microbial Control of Insects and Mites, 275-203, Academic Press, London (1971)
Borzani, W., Gregori, R. E., and Vairo, M. L. R. “Some observations on oscillatory changes in the growth rate of Saccharomyces cerevisiae in aerobic continuous undisturbed culture.” Biotechnol. Bioeng., 19, 1363-1374 (1977)
Bowman, L. and Geiger, E. “Optimization of fermentation conditions for alcohol production.” Biotechnol. Bioeng., 26, 1492-1497 (1984)
Box, G. E. P. and Wilson, K. N. “On the experimental attainment of optimum conditions.” J. R. Stat. Soc. Ser. B, 13, 1-45 (1951)
Bylund, F., Guillard, F., Enfords, S.-O., Tragardh, C., and Larsson, G., “Scale down of recombinant protein production: a comparative study of scaling performance.” Bioproc. Eng., 20, 377-389 (1999)
Campbell, D. P., Dieball D. E. and Brackett, J. M. “Rapid HPLC assay for the β-exotoxin of Bacillus thuringiensis.” J. Agric. Food Chem., 35, 156-158 (1987)
Cantwell, G. E., Dougherty, E., and Cantelo, W. W. “Activity of the b-exotoxin of Bacillus thuringiensis var. thuringiensis against the Colorado potato beetle and the ames test.” Enviro. Entomol., 12(5) 1424-1427 (1983)
Cheng, C., Hunag, Y. L. and Yang, S. T. “A novel feeding strategy for enhanced plasmid stability and protein production in recombinant yeast fedbatch fermentation.” Biotechnol. Bioeng., 56(1), 23-31 (1997)
Comberbach, D. M., Ghommidh, C., and Bu’Lock J. D. “Steady-state stability and dynamic behavior of continuous ethanol fermentation at high cell densities.” Enzyme Microb. Technol., 9, 676-684 (1987)
Couch, T. L. and Ross, D. A. “Production and utilization of Bacillus thuringiensis.” Biotechnol. Bioeng., 22, 1297-1304 (1980)
Dey, G., Mitra, A., Banerjee, R. and Maiti, B. R. “Enhanced production of amylase by optimization of nutritional constituents using response surface methodology.” Biochem. Eng. J., 7(3), 227-231 (2001)
De Vuyst, L. Van Loo, J. and Vandamme, E. J. “Two step fermentation process for improved xanthan production by Xanthomonas campestris NRRL-B-1459.” J. Chem. Technol. Biotechnol., 39, 263-273 (1987)
Dulmage, H. T. “Insecticidal activity of isolates of Bacillus thuringiensis and their potential for pest control.” In: Burges, H. D. (ed.) “Microbial Control of Pests and Plant Diseases 1970-1980”, Academic Press, London, UK, 193-222 (1981)
Franks, P. A., Hall, R. J. and Linklater, P. M. “Mechanistic model of the growth of Streptococcus cremoris HP at superoptimal temperatures.” Biotechnol. Bioeng., 22, 1465-1487 (1980)
Freyer, St., Weuster-Botz, D. and Wandrey, C. “Medium optimization using genetic algorithm.” BioEng., 8(5+6), 16-25 (1992)
Glazer, A. N. and Nikaido, H. “Microbial Biotechnology--Fundamentals of Applied Microbiology”, W. H. Freeman and Company, New York (1995)
Goldberg, I. and Er-el, Z. “The chemostat-An efficient technique for medium optimization.” Proc. Biochem., 16, 2-8 (1981)
Gu, Z., Lam, L. H. and Dhurjati, P. S. “Feature correlation method for enhancing fermentation development: a comparasion of quadratic regression with artificial neural networks.” Comput. Chem. Eng., 20, 407-412 (1996)
Hiller, W. M., Blanch, H. W., and Wilke, C. R. “A kinetic analysis of hybridoma growth and metabolism in batch and continuous suspension culture: Effect of nutrient concentration, dilution rate, and pH.” Biotechnol. Bioeng., 32, 947-965 (1988a)
Hiller, W. M., Blanch, H. W., and Wilke, C. R. “Transient responses of hybridoma metabolism to changes in the oxygen supply rate in continuous culture.” Bioproc. Eng., 3, 103-111 (1988b)
Hiller, W. M., Blanch, H. W., and Wilke, C. R. “Transient responses of hybridoma cells to lactate and ammonia pulse and step changes in continuous culture.” Bioproc. Eng., 3, 113-122 (1988c)
Holmberg, A., Sievanen, R., and Carlberg, G. “Fermentation of Bacillus thuringiensis for exotoxin production: Process analysis study.” Biotechnol. Bioeng., 22, 1707-1724 (1980)
Hsiun, D. Y. and Wu, W. T. “Mass transfer and liquid mixing in an airlift reactor with a net draft tube.” Bioproc. Eng., 12, 221-225 (1995).
Huang, T. K., Wang, P. M., and Wu, W. T. “Cultivation of Bacillus thuringiensis in an airlift reactor with wire mesh draft tubes.” Biochem. Eng. J., 7(1), 35-39 (2001)
Humphrey, A. “Shake flask to fermentor: what have we learned?” Biotechnol. Prog., 14, 3-7 (1998)
Jong, J. Z., Wu, W. T., Young, Y. H., and Tzeng, Y. M., “Morphological variation on cultivation of Bacillus thuringiensis for thuringiensin production.” Proceeding of the 3rd Asia-Pacific Biochemical Engineering Conference, 390-392 (1994)
Jong, J. Z., Hsiun, D. Y., Wu, W. T., and Tzeng, Y. M. “Fed-batch culture of Bacillus thuringiensis for thuringiensin production in a tower type reactor.” Biotechnol. Bioeng., 48, 207-213 (1995)
Kang, B. C., Lee, S. Y. and Chang, H. N. “Enhanced spore production of Bacillus thuringiensis by fed-batch culture.” Biotechnol. Lett., 14, 721-726 (1992)
Kennedy, M. J., Prapulla, S. G. and Thakuet, M. S. “Designing fermentation media: a comparison of neural networks and factorial design.” Biotechnol. Tech., 6, 293-398 (1992)
Koga, S., and Humphrey, A. E. “Study of the dynamic behavior of the chemostat system.” Biotechnol. Bioeng., 9, 375-386 (1967)
Kuhn, H., Friederich, U., and Fiecher, A. “Defined minimal medium for a thermophilic Bacillus sp. developed by a chemostat pulse and shift technique.” Eur. J. Appl. Microbiol. Biotechnol., 6, 341-349 (1979)
Lee, S. L. and Chen W. C. “Optimization of medium composition for the production of glucosyltransferase by Aspergillus niger with response surface methodology.” Enzyme Microb. Technol., 21, 436-440 (1997)
Levinson, B., Kasyan, K. J. and Chiu, S. S. “Identification of β-exotoxin production, plasmids encoding β-exotoxin and a new exotoxin in Bacillus thuringiensis by HPLC.” J. Bacteriol., 172, 3172-3179 (1990)
Lin, H. Y. and Neubauer, P. “Influence of controlled glucose oscillations on a fed-batch process of recombinant Escherichia coli.” J. Biotechnol., 79, 27-37 (2000)
Liu, B. L. and Tzeng, Y. M. “Optimization of growth medium for the production of spores from Bacillus thuringiensis using response surface methodology.” Bioproc. Eng. 18, 413-418 (1998)
Liu, C. H., Huang, C. F. and Liao C. C. “Medium optimization for glutathione production by Saccharomyces cerevisiae.” Proc. Biochem., 34(1), 17-23 (1999)
Lo, Y. M., Yang, S. T. and Min, D. B. “Effects of yeast extract and glucose on xanthan production and cell growth in batch culture of Xanthomonas campestris. Appl. Microbiol. Biotechnol., 47, 689-694 (1997)
Málek, I. “The physiological state of microorganisms during continuous culture.” In: Dawson, P. S. S. (Ed.), “Microbial Growth-Benchmark Papers in Microbiology.” Dowden, Hutchinson and Ross, USA (1974)
Malik, Z. and Rashid, K. “Comparison of optimization by response surface methodology with neurofuzzy methods.” IEEE Trans. Magn., 36(1), 241-257 (2000)
Marec, F., Matha, V. and Weiser, J. “Analysis of genotoxic activity of Bacillus thuringiensis b-exotoxin by means of drosophila wing spot test.” J. Inverte. Pathol., 53, 347-353 (1988)
Markl, H. and Bronnenmeier, R. “Mechanical stress and microbial production.” In: “Biotechnology”, vol. 2, Chap. 18, 369-392 (1985)
McConnell, E. and Richards, A. G. “The production by Bacillus thuringiensis Berliner of a heat-stable substance toxic for insects.” Canad. J. Microbiol., 6, 161-168 (1959)
McNeil, B., and Harvey, L. M., “Fermentation: A practical Approach”, IRL Press, New York (1990)
Mijnbeek, G. and Oosterhuis, N. M. G. “Strategies for scale up.” In: “Bioreactor Design and Product Yield”, Books in the BIOTOL series, Butterworth-Heinemann, Oxford, 7-48 (1992)
Mizobuchi, T., Shigyo, T., and Yano, T. “Stability and phase-plane analyses of continuous yeast culture on ammonium hydroxide: A complicated case.” J. Fermemt. Technol., 58(1), 39-45 (1980)
Montgomery, D. C. “Using fractional factorial designs for robust process development.” Quality Eng., 3, 193-205 (1991)
Moo-Young, M. and Blench, H. W. “Design of biochemical reactors: Mass transfer criteria for simple complex systems.” In: “Advances in Biochemcal Engineering”, Springer-Verlag, NewYork, 19, 1-69 (1981)
Neubauer, P., Häggström, L. and Enfors, S.-O. “Influence of substrate oscillations on acetate formation and growth yield in Escherichia coli glucose limited fed-batch cultivations.” Biotechnol. Bioeng., 47, 139-146 (1995)
Ohba, M., Tantichodok, A., and Aizawa, K. “Production of heat-stable exotoxin by Bacillus thuringiensis and Related Bacteria.” J. Inverte. Pathol., 38, 26-32 (1981)
Oosterhuis, N. M. G., Groesbeek, N. M., Olivier, A. P. C. and Kossen, N. W. F. “Scale-down aspects of the gluconic acid fermentation.” Biotechnol. Lett., 5(3), 141-146 (1983)
Page, M. R. and Cooper, R. D. “Scale-up of beta-exotoxin production in fed-batch Bacillus thuringiensis fermentation.” In Proceedings: 5th European Congress on Biotechnology, pp. 146-149, Copenhagen: Munskgaard (1990)
Parajό, J. C., Santos, V., Dominguez, H. and Vázquez, M. “NH4OH-based pretreatment for improving the nutritional quality of single-cell protein (SCP).” Appl. Biochem. Biotechnol., 55, 133-149 (1995)
Parekh, S., Vinci, V. A. and Strobel, R. J. “Improvement of microbial strains and fermentation processes.” Appl. Microbiol. Biotechnol., 54, 287-301 (2000)
Pickett, A. M. “Growth in a changing environment.” In: Bazin, M. J. (ed.), “Microbial Population Dynamics”, Chap. 4, 91-124, CRC Press, USA (1982)
Powell, K. A. and Jutsum, A. R. “Technical and commercial aspects of biocontrol products.” Pestic. Sci., 37, 315-321 (1993)
Rowe, G. E. and Margaritis, A. “Bioprocess developments in the production of bioinsecticides by Bacillus thuringiensis.” CRC Critical Rev. Biotechnol., 6, 87-127 (1987)
Sachidanandham, R., Jenny, K., Fiechter, A. and Jayaraman, K. “Stabilization and increased Production of insecticidal crystal proteins of Bacillus thuringiensis subsp. galleriae in steady and transient state continuous cultures.” Appl. Microbiol. Biotechnol., 47, 12-17 (1997)
Schugerl, K. “Comparison of the performances of stirred tank and airlift tower loop reactors” J. Biotechnol., 13, 251-256 (1990)
Sebesta, K., Farkas, J., and Horska, K. “Thuringiensin, the *-exotoxin of Bacillus thuringiensis.” In: Burges, H. D. (ed.), “Microbial Control of Pests and Plant Diseases 1970-1980”, 249-281, Academic Press, London, UK (1981)
Shih, C. C., Zuo, K. and Wu, W. T. “Optimal fed-batch culture for penicillin production via hybrid neural model and real coded genetic algorithm.” In Yoshida, T. and Shioya, S. (eds.), “Computer Application in Biotechnology CAB7, Osaka, Japan”, 51-54, Elsevier, Oxford (1998)
Sipkema, E. M., de Koning, W., Ganzeveld, K. J., Janssen, D. B., and Beenackers, A. A. C. M., “Experimental pulse technique for the study of microbial kinetics in continuous culture.” J. Biotechnol., 64, 159-176 (1998)
Sonnleitner, B., “Dynamic Adaptation of Microbes.” J. Biotechnol., 65, 47-60 (1998)
Sun, M. and Yu, Z. “Recent developments in the biotechnology of Bacillus thuringiensis” Biotechnol. Adv., 18, 143-145 (2000)
Tanigoshi, L. K., Mayer, D. F., and Babcock, H. M. “Efficacy of the *-exotoxin of Bacillus thuringiensis to Lygus hesperus.” J. Econ. Entomol., 83, 2200-2206 (1990)
Tzeng, Y. M. and Young, Y. H., “Production of thuringiensin from Bacillus thuringiensis using a net-draft-tube, modified airlift reactor.” World J. Microbiol. Biotechnol., 12, 32-37 (1996)
Vaňková, J., “The heat-stable exotoxin of Bacillus thuringiensis.” Folia Microbiol., 23, 162-174 (1978)
Vázquez, M. and Martin, A. M. “Optimization of Phaffia rhodozyma continuous culture through response surface methodology.” Biotechnol. Bioeng., 57, 314-320 (1996)
Vlasside, S., Ferrier, J. G. and Block, D. E. “Using historical data for bioprocess optimization: modeling wine charactiristics using artificial neural networks and archived process information.” Biotechnol. Bioeng. 73, 55-68 (2000)
Waitier, D., Dubourguier, H. C., Leguerinel, I. and Hornez, J. P. “Response surface models to describe the effects of temperature, pH, and ethanol concentration on growth kinetics and end products of a Pectinatus sp.” Appl. Environ. Microbiol., 62, 1233-1237 (1996)
Weuster-Botz, D. and Wandrey, C. “Medium optimization by genetic algorithm for continuous production of formate dehydrogenase.” Proc. Biochem., 30(6), 563-571 (1994)
Yamane, T. and Shimizu, S. “Fed-batch techniques in microbial processes.” Adv. Biochem. Eng. Biotechnol., 30, 47-94 (1984)
Yang, R. D. and Humphrey, A. E. “Dynamic and steady state studies of phenol biodegradation in pure and mixed cultures.” Biotechnol. Bioeng., 17, 1211-1235 (1975)
Yang, X. and Wang, S. S. “Development of Bacillus thuringiensis fermentation and process control from a practical perspective.” Biotechnol. Appl. Biochem., 28, 95-98 (1998)
Yano, T. and Koga, S. “Dynamic behavior of the chemostat subject to substrate inhibition.” Biotechnol. Bioeng., 11, 139-153 (1969)
Yano, T. and Koga, S. “Dynamic behavior of the chemostat subject to product inhibition.” J. Gen. Appl. Microbiol., 19, 97-114 (1973)
向明,“台灣生物農藥研發及其產業(一)”,農業世界,185,64-71 (1999)
吳美貌、曾耀銘、徐浩泰,“蘇力菌高產率醱酵暨高效液相層析全程偵測探討”,技術學刊,8(2),223-230 (1993)
陳能敏,“永續農業過去、現在、未來”,農業科學資科服務中心出版,台灣 (1996)
喻子牛,“蘇云金杆菌”,科學出版社,武漢,中國大陸 (1990)
熊定宇,“具網狀導流管氣舉式反應器之設計及其在蘇力菌醱酵上之應用”,清華大學化學工程研究所博士論文 (1995)
翟建富,“生物防治昆蟲病媒的新趨向”,生物產業,6(1),29-38 (1995)
劉炳嵐、曾耀銘,“醱酵法生產的微生物殺蟲劑-Bacillus thuringiensis”,科學發展月刊,17,1460-1473 (1989)
鍾建中,“網狀內管氣舉式反應器在蘇力菌素生產之應用”,清華大學化學工程研究所博士論文 (1994)

QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top