探討添加oxygen vector對Penicillium brevi-compactum在液態發酵中生產Mycophenolic acid及培養溫度對其在固態發酵鐘聲產產物之影響

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研究生：	陳冠州 Guan-Zhou Chen
論文名稱：	探討添加oxygen vector對Penicillium brevi-compactum在液態發酵中生產Mycophenolic acid及培養溫度對其在固態發酵鐘聲產產物之影響 Effects of Mycophenolic acid production by controlling oxygen supply on Penicillium brevicompactum and improvement by adding oxygen vectors on liquid state fermentation and temperature change on solid state fermentation
指導教授：	徐敬衡 Chin-Hang Shu
口試委員:
學位類別：	碩士 Master
系所名稱：	工學院 - 化學工程與材料工程學系 Department of Chemical & Materials Engineering
畢業學年度：	94
語文別：	中文
論文頁數：	112
中文關鍵詞：	通氣量、麥考酚酸、盤尼西林、固態發酵
外文關鍵詞：	oxygen vector, specific oxygen uptake rate, mycophenolic acid, penicillium brevi-compactum, aeration rate
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本研究利用培養Penicillium brevi-compactum生產Mycophenolic acid(MPA)，MPA用來作為器官移植時抑制免疫反應的藥物，作為Inositol MonoPhosphate DeHydrogenase（IMPDH）之非競爭型抑制劑。
??研究中利用攪拌式發酵槽調整發酵期間之通氣量(0.05vvm、0.2vvm、0.4vvm、0.5vvm、1.0vvm、1.2vvm、1.5vvm)，探討最佳的培養條件，最適合菌體生長的通氣量為1.5vvm，而對於菌體發酵生產MPA的產率來看，最適通氣量為1.0vvm。另外，由實驗結果發現通氣量=1.5vvm下的比生長速率（μ）最大，菌體生長所需要之時間最短，產物生產所需要的時間也最短。在添加oxygen vector的實驗中。藉由添加C14作為oxygen vector，在低通氣量中(0.05vvm)便可得到最佳MPA的產量，顯現添加oxygen vector，有利於Penicillium brevi-compactum生產MPA的製程。
??b固態發酵的探討上，發現菌體生長和MPA產量方面，攝氏28度是最適合的。

Effects of oxygen supply on the production, MPA production and product yield by Penicillium brevicompactum were evaluated by four air flow rate-controlled batch cultures. As the air flow rate was controlled as 0.05, 0.4, 0.5 ,1.0vvm of each batch, the maximum MPA concentration increased from 0.210 to 0.236 g/liter, and product yield (Yp/s) increased form 0.017 to 0.026. By adding 2%C14 (1-tetradecene ) as oxygen vector in the low oxygen supply condition, the batch (0.05vvm) performed similar fermentation kinetic as that of the sufficient oxygen supply condition(1.0vvm). Lower energy consumption in aeration system could be obtain by adding C14 in the batch culture.

第一章、緒論	1
1-1 研究動機	1
1-2 研究目的	3
第二章、文獻回顧	5
2-1真菌的介紹：	5
2-1-1黴菌的分類：	5
2-1-2青黴菌之介紹：	6
2-2 Mycophenolic acid之介紹	8
2-2-1 Mycophenolic acid之發現	8
2-2-2 Mycophenolic acid之生化合成	9
2-2-3 Mycophenolic acid在醫療上的用途	10
2-3 人體免疫系統和器官移植之介紹	11
2-3-1 人體免疫系統簡介	11
2-3-2 人體器官移植之簡介	12
2-3-2 人體器官移植時所使用的藥物	15
2-3-3  Mycophenolic acid應用在器官移值上	19
2-4 深層液態發酵培養	23
2-5 影響發酵的物理化學等環境生長因子	23
2-5-1 培養基組成	23
2-5-1.1 碳源	23
2-5-1.2 氮源	24
2-5-1.3 碳氮比	24
2-5-1.4 無機鹽類	24
2-5-2 攪拌速率	25
2-5-3 pH值	25
2-5-4 溶氧值(DO值)	26
2-5-5 溶氧值對於青黴菌之影響	27
2-5-6二氧化碳對青黴菌之影響	28
2-5-6溫度：	29
2-6發酵動態行為的數學模式	30
2-6-1與生長有關的產物(growth-associated product)	31
2-6-1與生長無關的產物(nongrowth-associated product)	31
2-7氧氣質傳對於菌體生長與MPA生成之影響：	32
2-8固態發酵培養的技術:	36
第三章、實驗規劃、材料與方法	43
3-1實驗規劃：	43
3-2實驗材料：	44
3-2-1實驗菌株：	44
3-2-3實驗藥品：	47
3-2-4實驗儀器與設備：	48
3-3實驗方法：	49
3-3-1菌體之接種及保存方法：	49
3-3-2發酵槽實驗：	50
3-3-3實驗分析方法：	50
第四章 實驗結果與討論	56
4-1 發酵槽培養實驗	56
4-2 發酵槽實驗之通氣量（aeration rate）對Penicillium brevicompactum 生產MPA之影響	57
4-2-1 發酵動力曲線的比較	57
4-2-2 SOUR值對於菌體生長的影響	63
4-2-3 SOUR值對於產物MPA的影響	64
4-3在通氣量為0.05vvm發酵槽中加入C14(1-Tetradecene)	67
4-3-1 發酵動力曲線的比較	67
4-3-2 添加C14值對於菌體生長的影響	71
4-2-3 添加C14值於產物MPA的影響	71
4-4討論溫度對P.  brevicompactum在固態發酵下產生MPA的影響	76
4-4-1 培養基的選擇	76
4-4-2 不同溫度下的發酵結果	79
4-4-3 水活性的重要性	86
第五章?結論與建議	89
5-1 結論	89
5-2 建議	91
第六章?參考文獻	92

                                

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