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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃慶璨(Ching-Tsan Huang) | |
| dc.contributor.author | Meng-Nan Tsai | en |
| dc.contributor.author | 蔡孟男 | zh_TW |
| dc.date.accessioned | 2021-06-14T16:56:43Z | - |
| dc.date.available | 2013-08-05 | |
| dc.date.copyright | 2008-08-05 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-07-30 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/40705 | - |
| dc.description.abstract | 嗜甲醇酵母菌Hansenula polymorpha是目前常用的異源蛋白質表現系統之一，可藉由強力且可調控的甲醇氧化脢啟動子(methanol oxidase promoter, MOXp)來表達異源蛋白質。甲醇氧化脢啟動子可經由甲醇誘導，也可藉由甘油或木糖的去抑制作用(derepression)表達異源蛋白質；但會受到六碳糖、雙醣及乙醇的抑制。在大規模的醱酵應用上，利用甲醇誘導表現異源蛋白質仍有許多困難。例如：甲醇具有毒性及易燃性而需增設防護設備；高濃度的甲醇不利於菌體生長，也會造成蛋白質產物降解；代謝甲醇時，需額外增加通氣量。為了避免上述甲醇誘導量產異源蛋白質的困難，本研究欲建立一個非甲醇誘導但仍兼顧嗜甲醇酵母菌系統優勢的表現系統。
在本研究中，成功地利用溶氧控制甘油的添加，於H. polymorpha產生去抑制作用，表現選殖自Neocallimastix frontalis的木聚醣脢Xyn11B’與Ganoderma microsporum的免疫調節蛋白質GMI。溶氧調控模式所得木聚醣脢活性為2219.42±94.05 U/ml，與甲醇誘導模式的2236.10±8.43 U/ml相當，且醱酵時間可從192小時縮短為60小時；免疫調節蛋白質GMI濃度則達到187.56±10.98 mg/l。這個新的表達系統不僅保留了原始MOXp的特性，更成功地利用甘油為碳源進行誘導表現異源蛋白質。 | zh_TW |
| dc.description.abstract | The methylotrophic yeast Hansenula polymorpha is one of the most commonly used platform for heterologous protein expression due to its strong and expression regulatable methanol oxidase promoter (MOXp). The MOXp can be induced by methanol and partially derepressed by glycerol or xylose, as well as repressed in the presence of hexoses, disaccharides or ethanol. There exist several disadvatages such as extra facility required to use this toxic and flammable compound, slow growth, recombinant protein degradation and extensive aeration, etc. when using methanol-induction at large scale production. In order to solve the above problems, it is necessary to establish an alternative induction mode without using methanol.
In this study, a new expression platform by using the derepression of H. polymorpha through the pO2 control was developed. A xylanase gene, xyn11B’, cloned from Neocallimastix frontalis and an immunomodulatory protein gene, gmi, cloned from Ganoderma microsporum were used to evaluate the derepression mode. The recombinant xylanase production reached 2219.42±94.05 U/ml after 60 h of induction by derepression in high cell density fermentation, compared to 2236.10±8.43 U/ml by methanol induction for 192 h. The expression level of GMI protein was 187.56±10.98 mg/l using the same approach. This improved expression platform prevented from the disadvantages of using methanol induction, while preserved the strong and regulatable nature of MOXp. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-14T16:56:43Z (GMT). No. of bitstreams: 1 ntu-97-R95B47410-1.pdf: 1838224 bytes, checksum: 6ab63cab8969f4ba74904367e456232e (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 口試委員會審定書 I
謝誌 II 謝誌 II 中文摘要 III Abstract IV 目錄 V 圖目錄 VII 表目錄 VIII 第一章 前言 1 1.1 表現系統 1 1.2 嗜甲醇酵母表現系統 4 1.3 多功能的細胞工廠Hansenula polymorpha 9 1.4 來自瘤胃真菌Neocallimastix frontalis的木聚醣脢 12 1.5 靈芝免疫調節蛋白質 14 1.6 研究動機與目的 17 第二章 材料與方法 19 2.1 菌株與培養條件 19 2.2 質體建構 19 2.3 質體轉形 25 2.4 轉形株篩選 25 2.5 醱酵槽大量生產目標蛋白質 26 2.6 木聚醣脢活性測定 28 2.7 西方雜合反應 28 2.8 酵素連結免疫分析法 29 2.9 甘油含量測定 30 2.10 南方氏雜合反應 30 第三章 結果 33 3.1 以溶氧調控生產重組木聚醣脢 33 3.2 GMI質體建構 42 3.3 H. polymorpha gmi轉形株篩選 44 3.4 H. polymorpha gmi轉形株小量培養分析 46 3.5 以H. polymorpha生產靈芝免疫調節蛋白質 49 3.6 轉形株南方氏雜合分析 54 第四章 討論 57 4.1 高細胞密度培養 57 4.2 去抑制作用與溶氧調控 57 4.3 去抑制作用的基因調控 60 第五章 結論 62 第六章 未來展望 63 第七章 參考資料 64 | |
| dc.language.iso | zh-TW | |
| dc.subject | 木聚醣脢 | zh_TW |
| dc.subject | 甲酸脫氫脢啟動子 | zh_TW |
| dc.subject | 多形漢遜氏酵母菌 | zh_TW |
| dc.subject | 甲醇氧化脢啟動子 | zh_TW |
| dc.subject | 去抑制作用 | zh_TW |
| dc.subject | 異源蛋白質表現 | zh_TW |
| dc.subject | 真菌免疫調節蛋白質 | zh_TW |
| dc.subject | MOX promoter | en |
| dc.subject | GMI | en |
| dc.subject | fungal immunomodulatory protein | en |
| dc.subject | xylanase | en |
| dc.subject | FMD promoter | en |
| dc.subject | Hansenula polymorpha | en |
| dc.subject | heterologous proteins | en |
| dc.subject | derepression | en |
| dc.title | 利用甘油受限誘導漢遜氏酵母菌表現重組蛋白質 | zh_TW |
| dc.title | Glycerol-limitation-induced production of recombinant proteins in Hansenula polymorpha | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 許瑞祥(Ruey-Shyang Hseu),張麗冠(Li-Kwan Chang),常怡雍(Yi-Yung Charng),陳浩仁(Hau-Ren Chen) | |
| dc.subject.keyword | 多形漢遜氏酵母菌,異源蛋白質表現,去抑制作用,甲醇氧化脢啟動子,甲酸脫氫脢啟動子,木聚醣脢,真菌免疫調節蛋白質, | zh_TW |
| dc.subject.keyword | Hansenula polymorpha,heterologous proteins,derepression,MOX promoter,FMD promoter,xylanase,fungal immunomodulatory protein,GMI, | en |
| dc.relation.page | 73 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2008-07-30 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 微生物與生化學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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