探討添加有機酸對Penicillium Brevicompactum在液態發酵中生產Mycophenolic acid之影響

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李慶彬(Ching-pin Li) 查詢紙本館藏

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化學工程與材料工程學系

論文名稱

探討添加有機酸對Penicillium Brevicompactum在液態發酵中生產Mycophenolic acid之影響
(Effects of organic acids on Mycophenolic acid product of Penicillium Brevicompactum in submerged fermentation)

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摘要(中)

Mycophenolic acid (MPA) 具有抗牛皮癬、抗真菌、抗細菌及抗病毒的能力，且已被證實為Inositol MonoPhosphate DeHydrogenase (IMPDH) 之非競爭型免疫抑制劑，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，因此在臨床上被用來預防器官移植所產生的排斥現象。實驗上利用微生物Penicillium brevicompactum進行深層液態發酵 (submerged fermentation) 來生產MPA。
本研究探討添加有機酸對P. brevicompactum生長及生產MPA的影響，其中發現於三羧酸循環中所代謝之有機酸如檸檬酸及琥珀酸能影響P. brevicompactum生長及產物代謝。在添加檸檬酸的情況下能促進菌體生長及加速碳源的消耗，提升菌體比生長速率 (μ) ，可達0.0189，為控制組的1.56倍，且能縮短發酵所需時間約25 hr，產率 (productivity) 提升為控制組的1.3倍；而添加琥珀酸則能提高MPA的產量及提升單位菌體對產物的轉化率 (Yp/x) ，以添加1 g/L達最高MPA產量0.536 g/L，約提升為控制組的1.27倍，單位菌體對產物的轉化率為60.06 mg/g，約為控制組1.33倍。

摘要(英)

Mycophenolic acid (MPA) has been to be antipsoriasis, antifungal, antibacterial and antiviral. It was demonstrated that MPA is a non-competitive immunosuppressive agent for Inositol MonoPhosphate DeHydrogenase (IMPDH) by inhibiting de novo purine biosynthesis of lymphocytes. Therefore, MPA is used clinically to prevent rejection of transplanted organs. In this study, Penicillium brevicompactum was used to product MPA in submerged fermentation.
Effects of various organic acids on cell growth and production of a useful bioactive metabolite, MPA, by submerged cultivation of Penicillium brevicompactum were investigated. The organic acid such as citric acid and succinic acid, which present in the tricarboxylic acid cycle, were found to affect the cell growth and its metabolism.
Addition of citric acid stimulated cell growth, increased consumption rate of carbon source and reduced fermentation time about 25 hr.The specific growth rate and productivity were 1.56 and 1.3 times than that of control-level, respectively. In addition, addition of succinic acid under 1 g/L concentration increased MPA production to 0.536 g/L, which was 1.27 times than that of control-level. Meanwhile the Yp/x increased 1.33 times than that of control-level.

關鍵字(中)

★ 麥考酚酸
★ 有機酸
★ 短密青黴菌

關鍵字(英)

★ organic acids
★ Penicillium brevicompactum
★ Mycophenolic acid

論文目次

摘要 I
Abstract II
目錄 III
圖目錄 VI
表目錄 VIII
第一章緒論 1
1.1 研究動機 1
1.2 研究目的 2
第二章文獻回顧 3
2.1微生物發酵產業 3
2.2 青黴菌 3
2.2.1真菌介紹 3
2.2.2真菌的分類 4
2.2.3青黴菌之介紹 6
2.2.4 藥用抗生素的時代 7
2.3 Mycophenolic acid之介紹 8
2.3.1 Mycophenolic acid 之發現 8
2.3.2 Mycophenolic acid之生化合成 9
2.3.3 Mycophenolic acid在醫療上之應用 10
2.4 人體免疫系統和器官移植之簡介 11
2.4.1人體免疫系統簡介 11
2.4.2器官移植簡介 12
2.4.3器官移植免疫學 12
2.4.4器官排斥 14
2.4.5人體器官移植時所使用的藥物 16
2.4.6免疫抑制劑 17
2.4.7 Mycophenolic acid應用在器官移植上 19
2.5 有機酸 22
2.5.1有機酸的介紹 22
2.5.2有機酸於發酵中的應用 22
2.5.3 添加有機酸之考量因素 26
第三章材料與方法 33
3.1實驗規劃 33
3.2 實驗材料 34
3.2.1 實驗藥品 34
3.2.2實驗儀器及其他設備 36
3.2.3 實驗裝置 38
3.3 實驗菌株與方法 38
3.3.1實驗菌株 38
3.3.2 培養基組成 39
3.4實驗方法 40
3.4.1菌種接種及保存方法 40
3.4.2發酵培養 41
3.4.2.1 添加不同濃度乙酸之搖瓶實驗 41
3.4.2.2 添加不同的有機酸於相同濃度下之搖瓶實驗 41
3.4.2.3 添加不同濃度檸檬酸之搖瓶實驗 42
3.4.2.4添加不同濃度琥珀酸之搖瓶實驗 42
3.4.2.5 添加檸檬酸對P. brevicompactum的影響之發酵槽實驗 42
3.4.2.6 添加琥珀酸對P. brevicompactum的影響之發酵槽實驗 43
3.4.3實驗分析方法： 43
3.4.3.1發酵液處理流程 43
3.4.3.2菌重分析 45
3.4.3.3殘糖(Sucrose)及有機酸分析 45
3.4.3.4產物濃度 (MPA) 之分析 48
第四章實驗結果與討論 49
4.1 添加乙酸對Penicillium brevicompactum生產Mycophenolic acid的影響 49
4.1.1 搖瓶實驗 49
4.1.2 發酵動力曲線圖 52
4.2 探討不同有機酸對Penicillium brevicompactum生長及生產 53
4.3 探討不同濃度之檸檬酸對Penicillium brevicompactum生長的影 56
4.3.1 搖瓶實驗 56
4.3.2 發酵動力曲線圖 59
4.4 探討不同濃度之琥珀酸對Penicillium brevicompactum生產 MPA的影響 64
4.4.1 搖瓶實驗 64
4.4.2 發酵動力曲線圖 65
第五章結論與建議 71
5.1 結論 71
5.1.1 乙酸對P. brevicompactum生產MPA的影響 71
5.1.2 有機酸對P. brevicompactum生長及生產MPA的影響 71
5.2 建議 71
第六章參考文獻 72

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指導教授

徐敬衡(Chin-hang Shu)

審核日期

2009-7-16

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