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研究生:蘇誌賢
研究生(外文):Chih-Hsien Su
論文名稱:嗜熱性真菌 Myceliophthora heterothallica 之化學成分及其生物活性研究
論文名稱(外文):Studies on the Chemical Constituents and Their Biological Activities of the Thermophilic Fungus, Myceliophthora heterothallica
指導教授:吳世雄吳世雄引用關係
口試委員:楊玉良鄭偉杰
口試日期:2013-07-24
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:生化科學研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:英文
論文頁數:78
中文關鍵詞:嗜熱性真菌Myceliophthora heterothallica抗癌活性抗菌活性天然物純化
外文關鍵詞:Myceliophthora heterothallicathermophilic fungusnatural product purificationanti-bacteria activityanti-cancer activity
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本研究的目的在於尋找真菌Myceliophthora heterothallica中具有生物活性
的天然物,並且期望可以得到過去文獻未發現的新化合物,Myceliophthora
heterothallica 的培養溫度為45℃,初步的活性測試顯示此真菌的乙酸乙酯萃取物有良好的抗癌和抗菌活性,為了瞭解Myceliophthora heterothallica 具有生物活性的化合物為何,在研究中以大量培養的方式以取得較為大量的萃取物,之後再以不同的純化方式進行純化,並以質譜和核磁共振的方式解出化合物的結構。

研究中得到了十二個化合物,其中包含了十一個已知化合物及一個先前未被發表的化合物。而除了分離和純化之外,這些純化後的化合物進行了包括了抗癌活性和抗菌活性生物活性的測試, 實驗結果發現其中有一個化合物具有抗菌的活性是先前未被報導過的,之後這些化合物的其他生物活性或是作用機制或許可以在之後的研究中繼續探討。


The aim of this research is to search for bioactive secondary metabolites from the fungus Myceliophthora heterothallica in order to obtain compounds not previously reported in the literature. Myceliophthora heterothallica was cultured at 45 ℃. Preliminary bioactivity tests showed that the EtOAc crude extract showed good bioactivity on anti-cancer and anti-bacteria bioassays. In order to identify the bioactive compounds of Myceliophthora heterothallica, the fungi was large-scale cultured to obtain large amounts of fungi extract. After extraction, various purification methods (gel filtration, SiO2 open column, HPLC) were applied to purify the bioactive compounds and the purified compounds were identified by NMR and mass spectroscopy.
There were twelve compounds obtained in this study, including eleven known and one compound never reported previously. In addition to purification of compounds, anti-bacteria and anti-cancer bioactivity was tested. A known compound was shown to exhibit previously unreported anti-bacterial activity which warrants further research into its mechanism and biochemistry.


摘要 II
Abstract III
致謝 V
Contents VI
Content of Figures IX
Content of Tables XIV
Chapter 1 1
INTRODUCTION 1
1.1 Thermophilic Fungi 1
1.2 Myceliophthora heterothallica 2
1.3 Literature Review of Myceliophthora 4
Waol A and B: 4
Estatin A and B: 5
Myceliothermophins A–E: 5
1.4 Objective 7
Chapter 2 9
MATERIALS AND METHODS 9
2.1 Materials 9
2.1.1 Fungi Strains 9
2.1.2 Medium for Myceliophthora heterothallica 9
2.1.3 Instruments 10
2.2 Methods 11
2.2.1 Flow Chart 11
2.2.2 Bioactivity Screening 11
2.2.3 Extraction, Isolation and Purification 12
2.2.4 Bacteria Culture 14
2.2.5 ITS region sequence identification for fungi 14
Chapter 3 16
RESULTS 16
Bioactivity-guided Compound Purification 16
Chapter 4 20
Structure Elucidation and Their Bioactivities 20
4.1 Cyclo(Ile-Pro) (1) 20
4.2 Cyclo(Val-Pro) (2) 24
4.3 Cyclo(Tyr-Pro) (3) 28
4.4 Cyclo(Phe-Pro) (4) 32
4.5 Cyclo(Phe-Leu) (5) 36
4.6 Bisdethiobis(methylthio)gliotoxin (6) 40
4.7 Phenylacetic acid (7) 44
4.8 4-Hydroxy-benzaldehyde (8) 47
4.9 Demethylmacrosporine (9) 49
4.10 Chaetochromin (10) 52
4.11 UCS1025B (11) 56
4.12 Compound 12 (12) 63
4.13 Pure compound Biological Activities 68
4.13.1 Anti-bacteria activity 68
4.13.2 Anti-cancer activity 69
Chapter 5 71
Discussion 71
Reference 75


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