探討添加界面活性劑Tween 80 對Penicillium brevicompactum 在液態發酵中生產Mycophenolic acid 之影響

Effects of surfactant Tween 80 on the production of Mycophenolic acid by Penicillium brevicompactum in batch culture

羅心怡(Hsin-Yi Lo)

指導教授 ： 徐敬衡

國立中央大學/工學院/化學工程與材料工程學系/碩士(2008年)

摘要

自器官移植的歷史揭開序幕之後，如何降低排斥的現象，一直是醫界致力解決的問題，因應而生的即是抗排斥的藥物。本研究中的Mycophenolic acid (MPA)是用來作為器官移植時抑制免疫反應的藥物，作為Inositol MonoPhosphate DeHydrogenase (INPDH)之非競爭型抑制劑，針對淋巴細胞之合成路徑進行抑制而達到降低免疫反應的發生，而實驗所使用微生物是Penicillium brevicompactum進行深層液態發酵(submerged fermentation)生產MPA。
　　為了提高P. brevicompactum生產Mycophenolic acid的產量，本研究採用深層液態發酵的方式，以添加界面活性劑Tween 80作為變因探討Mycophenolic acid的產量，並進一步了解發酵過程中界面活性劑Tween 80扮演的角色及其對生產Mycophenolic acid的影響。
　　整體而言添加界面活性劑Tween 80對於P. brevicompactum生產Mycophenolic acid是有正面幫助。本研究得到的結論為當添加界面活性劑Tween 80為0.2%時得到最佳Mycophenolic acid產量為0.512 g/l，提升1.6倍之多；Productivity提升2.1倍為4.196 mg/hr。藉由KLa及SOUR 推測Tween 80的添加扮演促進氧氣傳送的角色，且添加Tween 80也會改變其P. brevicompactum的菌體的型態，又以有緻密核心且外圍毛茸鬆散狀的菌球有最佳的MPA產量。

關鍵字

青黴菌 ； 麥考酚酸 ； 界面活性劑

並列摘要

Mycophenolic acid (MPA) is a organic acid and had been discovered as early as 1983 by an Italian physician. MPA against to bacteria, fungi, viruses, toumours, psoriasis, and inhibit the grorth of the anthrax bacillus. Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid, an inhibitor of inosin monophosphate dehydrogenase (IMPDH).Mycophenolate mofetil (MMF), an ester of mycophenolic acid, has been widely used as an immunosuppressant in kidney, heart, and liver transplantationand as a medication to treat other ailments.

Oxygen transport rates limit the productivites of aerobic fermentations. Penicillium brevicompactum is an aerobic microorganism and improve cell growth by supplying sufficient oxygen. In this study, dissolved oxygen in the fermentation medium plays an important environment factor to affect not only cell growth but also MPA concentration. As the air flow rate was controlled as 0.2vvm、0.5vvm of each batch ,the maximum MPA concentration increased from 0.324 g/l to 0.462 g/l ; Product yield rate increased from25.9 mg/g to 36.9 mg/g. Tween80 addition had shown to increase cell growth and MPA production. The highest MPA production, 0.512 g/l, were obtained when 0.2 % Tween80 were added, which was 1.6-fold of the control. The productivity increased 2.1-fold of the control. Surfact-active substances affect pellet growth. With Penicillium brevicompactum, the large pellets develop with the outer hairy region of pellets when Tween80 was added.

並列關鍵字

Mycophenolic acid ； Tween 80 ； Penicillium brevicompactum

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