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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 黃慶璨(Ching-Tsan Huang) | |
dc.contributor.author | Chia-Wei Lin | en |
dc.contributor.author | 林佳葳 | zh_TW |
dc.date.accessioned | 2021-06-08T02:23:18Z | - |
dc.date.copyright | 2015-08-28 | |
dc.date.issued | 2015 | |
dc.date.submitted | 2015-08-19 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19855 | - |
dc.description.abstract | 菇類分子農場 (mushroom molecular pharming) 係以菇類為生物反應器,生產醫藥用蛋白質或工業用酵素,具備安全性高、製程簡單和成本低廉等優勢,為現今生物產業應用之新趨勢。過去研究以農桿菌媒介轉形法成功建立菇類轉形平台,應用於多種菇類上。前人為提升轉基因菇類的生物安全性,將琥珀酸脫氫酶 (succinate dehydrogenase, Sdh) 之次單元B (SdhB) 上胺基酸單一點突變成為萎鏽靈抗性基因cbrB,建立以金針菇為材料來源之同源性篩選系統。然而後續應用卻發現此抗性篩選系統並不如預期穩定。因此,本篇研究欲發展以次單元C (SdhC) 為基礎之萎鏽靈抗性基因cbrC,並比較帶有兩段抗性基因之轉形株的琥珀酸脫氫酶活性,找出活性較高之萎鏽靈抗性篩選標誌。實驗結果證實帶有cbrC 之金針菇轉形株確實可生長在萎鏽靈篩選培養基上,顯示 cbrC 確實具有萎鏽靈抗性能力,而內含子的存在可幫助金針菇表現cbrC。本篇研究建立菇類琥珀酸脫氫酶活性測試系統,抽取轉形株粒線體進行活性分析,實驗結果發現在含有萎鏽靈抗生素之環境下,轉形株之酵素活性皆比野生株高,而帶有 cbrC 的轉形株活性較帶有 cbrB的轉形株活性高,顯示菇類同源性篩選系統以 SdhC 為較佳的篩選標誌。而未來希望能結合兩段抗性基因以提高此同源篩選系統之為萎鏽靈抗性能力。 | zh_TW |
dc.description.abstract | Mushroom molecular pharming, a novel and promising industry that use mushrooms as bioreactors to produce pharmaceutical proteins or industrial enzymes, possesses lots of advantages such as safety, easy manipulation and low cost. In our laboratory, we have been successfully established Agrobacterium-mediated transformation in mushroom system. For biosafety of transgenic mushrooms, we also developed homologous selectable system via a single point mutation of succinate dehygrogenase subunit B (SdhB) to make transformants against harmless agent, carboxin. However, previous study show the instability of transformants after several generations of subcultures. In order to improve the efficiency of selection and stability of transformants, we would like to clone another carboxin-binding site of succinate dehydrogenase to enhance the selectable resistance against carboxin. In this study, succinate dehygrogenase subunit C (SdhC) was selected as the target sequence of novel selectable marker. We successfully cloned carboxin-resistance gene (cbrC) based on the SdhC, and found out that gpd-d1 promoter with the first intron improved the expression of cbrC. The activity of succinate dehydrogenase was assaged to compare these two selectable system, SdhB (cbrB) and SdhC (cbrC). The results suggested that carboxin-resistance gene (cbrC) based on the SdhC is a better carboxin resistance selection marker than that based on SdhB. We demonstrated that carboxin-resistance gene (cbrC) based on the SdhC is a new homologous selectable marker, and its seleciotn ability was measured by the succinate dehydrogenase activity in mushrooms. This allows us to develop a dual carboxin-resistant selectable system to improve the stability of transgenic mushrooms. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T02:23:18Z (GMT). No. of bitstreams: 1 ntu-104-R02b22017-1.pdf: 5419784 bytes, checksum: ccd200608ede9c1dd36ec824476d9476 (MD5) Previous issue date: 2015 | en |
dc.description.tableofcontents | 謝誌 2
摘要 I Abstract II 中英文縮寫對照表 III 目錄 IV 圖目錄 VIII 附圖目錄 X 表目錄 XI 第一章 前言 1 一、 分子農場 1 1. 植物分子農場之現況 1 2. 植物分子農場之優勢 2 3. 植物分子農場面臨之問題 3 二、 菇類分子農場 4 1. 菇類分子農場之優勢與發展 4 三、 金針菇 6 1. 形態特徵與分類地位 6 2. 栽培優勢與市場價值 6 3. 藥理活性與應用 7 四、 菇類異源表現系統 9 1. 轉形策略 9 2. 農桿菌媒介轉形法 10 3. 報導基因 11 4. 分生策略提升異源蛋白質之表現量 12 5. 篩選標誌 13 五、 菇類分子農場面臨之問題 15 1. 同源性金針菇萎鏽靈抗性篩選系統面臨之問題 15 六、 研究動機與目標 16 第二章 材料與方法 18 一、 實驗菌株與培養條件 18 1. 金針菇菌絲 18 2. 大腸桿菌Escherichia coli EPI300 18 3. 農桿菌Agrobacterium tumefaciens LBA4404 18 二、 核酸引子序列 18 三、 金針菇琥珀酸脫氫酶基因sdhC選殖 20 1. 金針菇染色體DNA萃取 20 2. 部分保守性 DNA 序列 22 3. sdhC全長基因之釣取 22 四、 表現質體 27 五、 農桿菌電穿孔轉形 29 1. 農桿菌勝任細胞製備 29 2. 農桿菌電穿孔轉形 29 3. 農桿菌轉形株篩選 30 六、 金針菇農桿菌媒介轉形 32 1. 菇類轉形材料製備 32 2. 農桿菌培養與前處理 32 3. 農桿菌與真菌共培養 32 4. 選擇性培養基抗生素濃度選擇 33 5. 選擇性培養基篩選 33 七、 金針菇轉形株篩選與分析 35 1. 聚合酶連鎖反應檢測 (Polymerase chain reaction; PCR) 35 2. 轉形株最小抑制濃度測試 35 八、 琥珀酸脫氫酶活性測試 36 1. 粗萃取粒線體蛋白質 36 2. 建立Succinate-DCIP reductase測試系統 36 第三章 實驗結果 40 一、 金針菇單一點突變同源性琥珀酸脫氫酶基因sdhC篩選系統建立 40 1. 完整金針菇琥珀酸脫氫酶基因sdhC選殖與定點突變 40 2. 農桿菌電穿孔轉形 50 3. 金針菇農桿菌媒介轉形 52 二、 CbrC篩選系統之抗性能力 56 1. 轉形株最小抑制濃度測試 56 2. 琥珀酸脫氫酶活性 58 第四章 討論 64 一、 金針菇單一點突變同源性琥珀酸脫氫酶基因sdhC篩選系統建立 64 1. SdhC基因選殖與胺基酸預測 64 2. 萎鏽靈抗性確認 65 3. 不同啟動子之萎鏽靈抗性抗性基因表現 65 4. 金針菇單核菌絲轉形 66 二、 金針菇單一點突變同源性CbrC篩選系統之抗性能力 71 1. 不同抗生素濃度培養轉形株與內含子影響 71 2. 琥珀酸脫氫酶活性測試 72 3. 轉形株抗性能力 72 第五章 結論 75 第六章 未來展望 76 第七章 參考文獻 77 第八章 附錄 86 | |
dc.language.iso | zh-TW | |
dc.title | 金針菇琥珀酸脫氫酶次單元C基因選殖及不同萎鏽靈抗性基因比較 | zh_TW |
dc.title | Cloning succinate dehydrogenase subunit C gene and comparison of different carboxin resistance gene for homologous selectable system in Flammulina velutipes | en |
dc.type | Thesis | |
dc.date.schoolyear | 103-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 許瑞祥(Ruey-Shyang Hseu),楊啟伸(Chii-Shen Yang),林晉玄(Ching-Hsuan Lin),陳浩仁(Hau-Ren Chen) | |
dc.subject.keyword | 菇類分子農場,金針菇,同源性篩選系統,萎鏽靈抗性基因,琥珀酸脫氫?活性,琥珀酸脫氫?次單元C, | zh_TW |
dc.subject.keyword | Mushroom molecular pharming,Flammulina velutipes,carboxin resistance selectable marker,Succinate dehygrogenase activity,SdhC, | en |
dc.relation.page | 90 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2015-08-19 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科技學系 | zh_TW |
顯示於系所單位: | 生化科技學系 |
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