不良的飲食習慣、惡劣的生活環境以及壓力，皆可能引發人體產生大量的自由基，而超氧歧化酶 (superoxide dismutase，SOD) 可幫助人體清除過多的自由基，來預防疾病及老化。常見的SOD類型可分為兩種，存在於粒線體膜空間以及真核細胞中的Cu-Zn-SOD，還有粒線體基質及細菌中的Mn-SOD。目前市面上的SOD大多自牛紅血球分離而得的 Cu-Zn-SOD ，或者利用細菌發酵產生的 Mn-SOD。根據過去研究指出，酵母菌中具有Cu-Zn-SOD 與 Mn-SOD之酵素，但活性不高，故本研究欲篩選具高SOD活性之酵母菌進行發酵，並探討能否利用固態發酵提升SOD活性產量。首先，從自然界中篩選酵母菌，並測試其對酒精和雙氧水的耐受性、DPPH自由基清除能力，以及SOD活性產生的穩定性進行菌株確認。而菌株之鑑定結果為Meyerozyma guilliermondii，接著進行菌株產生SOD活性之最適化探討，其液態發酵最佳條件為在3% (w/v)葡萄糖、0.5% (w/v)大豆蛋白，調整起始pH值為9，接種3% (v/v)之酵母菌於35℃、150 rpm，培養96小時後能產生最高活性71.0 U/mL，並接種至固態基質中探討菌株產生SOD活性之最適固態發酵條件，其固態發酵最佳條件為以碎麥做為固態基質，添加3% (w/w)葡萄糖、25 μmol/L ZnSO4˙7H2O、接種15% (v/w)發酵液，並調整其最終水分含量為70% (v/w)，置於35℃通氣培養96小時後能產生最高活性161.9 U/gds (g-dry solid)。

Unhealthy diet, poor living environment and stress will trigger production of large amounts of free radicals in body. Superoxide dismutase (SOD) can help to get rid of the extra free radicals in human body and thereby to prevent diseases and aging. There are common by two types of SOD. One is called Cu-Zn-SOD. It presents in intermembrane space (IMS) of mitochondria and eukaryotes. The other one is called Mn-SOD which is in the mitochondrial matrix and bacteria. Most SOD sold in the current market’s is either Cu-Zn-SOD isolated from bovine red blood cells, or Mn-SOD, produced from bacteria fermentation. According to past studies, yeast can produce both Cu-Zn-SOD and Mn-SOD. However, the activity was low. In current study, we want to isolate a yeast with high SOD activity and to see if solid-state fermentation (SSF) can enhance SOD production. Yeasts were isolated from natural sources and tested their tolerance of alcohol and hydrogen peroxide, DPPH free radical scavenging ability and stability produced by SOD activity. After this we can confirm the yeast. The strain was identified as Meyerozyma guilliermondii. The optimum conditions for liquid-state fermentation(LSF) were 3%(w/v) glucose, 0.5%(w/v) soy protein and incubated with 3%(v/v) inoculum ratio of yeast at initial pH=9, 35℃, 150 rpm. The highest SOD activity was 71.0 U/mL after 96 hours and then inoculated into the solid substrate to explore the optimum conditions for the production of SOD activity in SSF. The optimum conditions for SSF were used broken wheat as solid substrate, added 3%(w/w) glucose, 25 μmol/L ZnSO4˙7H2O and inoculated with 15%(v/w) LSF at initial pH=9, 35℃, 70%(v/w) final moisture content. After 96 hours aerobic incubation can produce the highest SOD activity was 161.9 U/gds.

中文摘要 I
Abstract III
目錄 V
圖目錄 X
表目錄 XIII
壹、前言 1
貳、文獻回顧 2
一、自由基 2
(一) 自由基之介紹 2
(二) 活性氧化物質(reactive oxygen species, ROS) 2
(三) 活性氧化物質來源 4
(四)自由基對人體的傷害 4
二、超氧歧化酶(Superoxide dismutase; SOD) 9
(一) 超氧歧化酶之介紹 9
(二) 超氧歧化酶之分類 10
1. 銅鋅型超氧歧化酶(Cu/Zn-SOD) 12
2. 錳型超氧歧化酶 14
3. 鐵型超氧歧化酶 16
三、酵母菌 18
(一) 酵母菌的定義 18
(二) 酵母菌之分類 18
(三) 分離菌株Meyerozyma(Pichia) guilliermondii之簡述 19
(四) 酵母菌株的SOD 20
四、超氧歧化酶之發酵生產 24
(一) 液態發酵生產SOD 24
(二) 固態發酵生產SOD 24
五、固態發酵 26
(一) 固態發酵的介紹 26
(二) 固態發酵的應用 26
(三) 固態發酵的優缺點 29
参、材料方法 30
一、實驗材料 30
(一)實驗菌株 30
1. 酵母菌 30
(二)培養基 30
(三)分析藥品之配製 31
(四) 藥品與材料 32
(五)儀器與設備 32
二、實驗流程 33
(一)菌種篩選 33
(二)挑選高生產SOD活性之酵母 34
(三)固態發酵 35
三、實驗流程 36
(一)菌株篩選 36
1. 酵母菌株之分離純化與保存 36
2. 酵母菌株之保存 36
(二)超氧歧化酶之酵母菌株篩選 37
1. 超氧歧化酶活性測定 37
2. 酵母菌之酒精抑制實驗 38
3. 酵母菌之雙氧水抑制實驗 38
4.酵母菌生產SOD活性之穩定性 38
5. DPPH 自由基清除能力測定 38
(三) 酵母菌在YM中生長曲線 39
(四) 液態培養基產生SOD活性之最適化探討 39
1. 最適氮源之探討 39
2. 最適氮源濃度之探討 39
3. 最適碳源之探討 40
4. 最適碳源濃度之探討 40
5. 最適無機鹽類之探討 40
6. 最適無機鹽類濃度之探討 40
7. 最適培養基起始pH值之探討 41
8. 最適培養之震盪速率探討 41
9. 最適接種量之探討 41
10. 最適培養之溫度探討 41
11. 在不同培養時間下對菌株生長之影響 41
12. 不同金屬離子對菌株產生SOD之影響 42
13. 利用5L發酵槽之擴大培養 42
(五) 固態培養產生SOD活性之最適化探討 43
1.最適固態發酵基質之探討 43
2.最適固態發酵基質混合比例之探討 43
3.最適水分含量對固態發酵生產SOD之影響 43
4.不同培養溫度對固態發酵生產SOD之影響 43
5.於固態基質中額外添加碳氮源對菌株生產SOD活性之影響 44
6.額外添加特定金屬鹽類對菌株生產SOD活性增加之影響 44
7.額外添加不同濃度金屬鹽類對菌株生產SOD活性增加之影響 44
8.不同接種量對菌株在固態發酵中生產SOD活性增加之影響 44
9.固態發酵條件下菌株之生長曲線探討 45
肆、結果與討論 46
一、酵母菌之分離與篩選 46
二、酵母菌初步篩選 46
(一) 酵母菌發酵 46
(二) 酵母菌對酒精抑制實驗 46
(三) 酵母菌對雙氧水抑制實驗 47
(四) 酵母菌生產SOD活性之穩定性 47
(五) DPPH 自由基清除能力 48
(六) 28S rRNA菌株鑑定 48
三、M. guilliermondii NPUST Y23在YM中生長曲線 48
四、液態培養基產生SOD活性之最適化探討 60
(一) 不同氮源對M. guilliermondii NPUST Y23生產SOD活性之 影響 60
(二) 最適氮源濃度對M. guilliermondii NPUST Y23生產SOD活 性之影響 60
(三) 不同碳源對M. guilliermondii NPUST Y23生產SOD活性之 影響 63
(四) 最適碳源濃度對M. guilliermondii NPUST Y23生產SOD活 性之影響 63
(五) 不同無機鹽類對M. guilliermondii NPUST Y23生產SOD活 性之影響 66
(六) 最適NaCl濃度對M. guilliermondii NPUST Y23生產SOD活 性之影響 66
(七) 培養基不同pH值對M. guilliermondii NPUST Y23生產SOD 活性之影響 69
(八) 不同震盪速率對M. guilliermondii NPUST Y23生產SOD活 性之影響 69
(九) 不同接種量對M. guilliermondii NPUST Y23生產SOD活性 之影響 69
(十) 不同培養溫度對M. guilliermondii NPUST Y23生產SOD活 性之影響 73
(十一) M. guilliermondii NPUST Y23於最適培養基中之生長曲線 73
(十二) 添加金屬離子對產生SOD活性之影響 74
(十三) 利用5L發酵槽之擴大培養 74
五、利用固態培養產生SOD活性之最適化探討 79
(一) 最適固態發酵基質之探討 79
(二) 最適固態發酵基質混合比例對M. guilliermondii NPUST Y23 在固態發酵中產生SOD活性之影響 79
(三) 在基質中之最適水分含量對M. guilliermondii NPUST Y23在 固態發酵中產生SOD活性之影響 83
(四) 不同培養溫度對M. guilliermondii NPUST Y23在固態發酵中 產生SOD活性之影響 83
(五) 於固態基質中額外添加碳氮源對M. guilliermondii NPUST Y23在固態發酵中產生SOD活性之影響 83
(六) 額外添加特定金屬鹽類對M. guilliermondii NPUST Y23在固 態發酵中產生SOD活性之影響 87
(七) 額外添加不同濃度金屬鹽類對M. guilliermondii NPUST Y23 在固態發酵中產生SOD活性之影響 87
(八) 不同接種量對M. guilliermondii NPUST Y23在固態發酵中產 生SOD活性之影響 90
(九) 最適固態發酵條件下對M. guilliermondii NPUST Y23之生長 曲線 90
伍、結論 93
陸、參考文獻 94
作者簡介 105

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