探討深層發酵中環境因子對巴西洋菇生產多醣之影響

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文博均(Bor-Juin Wen) 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

探討深層發酵中環境因子對巴西洋菇生產多醣之影響
(The influence of environmental conditions on polysaccharide formation by Agaricus blazei in submerged culture)

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摘要(中)

針對巴西洋菇的發酵技術研究與開發，國內雖起步較慢，不過最近幾年已有相關產品上市，但有關發酵生物程序（bioprocess）中物理因子對巴西洋菇生產

摘要(英)

Polysaccharides isolated from certain mushrooms possess anti-tumor activity in animal models. Agaricus blazei Murill (Himematsutake) has stronger anti-tumor activity against Sarcoma 180 in mice than do polysaccharides from Ganoderma lucidum, Lentiuu edodes, and Coriolus versicolor. Nevertheless, improving production of polysaccharide from mycelial fungus A. blazei has received relatively little attention.
Agitation is the major process parameter influencing oxygen transfer, shear, and fermentation mixing performance. Oxygen mass transfer inevitably changes with shear field, thus, leading to contradictory conclusions. For example, pullulan, a polysaccharide from Aureobasidium pullulans, improved with increased agitation speed, but was optimized by low shear stress and dissolved oxygen tension. Intense shear fields in bioreactors damage cell growth and metabolite yields of filamentous fungi. Shear protectants such as serum, and Pluronics have been successfully established in animal cell cultures, and various mechanisms have been proposed including turbulence dampening, and suppression of cell attachment to bubbles. Furthermore, adding protectants was observed to have a negative effect on oxygen transfer for example reducing the value of the volumetric oxygen transfer coefficient kLa. Successes using filamentous cultures have been limited. Consequently, the supplementing of water-soluble polymers to a shear-sensitive filamentous culture may create a shear-protecting and oxygen-limiting environment for the biosynthesis of polysaccharide. This study demonstrates a fermentation strategy for enhancing polysaccharide production of Agaricus blazei in xanthan supplemented culture via shear protection and oxygen limitation.
Xanthan supplementation has been shown to provide shear protection and polysaccharide stimulation of Agaricus blazei. In xanthan-free cultures, the optimal cell yield, 0.63 g biomass/g glucose, and product yield, 0.19 g polysaccharide/g glucose, of the xanthan-free cultures occurred when the critical impeller tip speed was 50.3 cm/s and 100.5 cm/s, respectively. Furthermore, the critical impeller tip speed of cell yield shifted from 50.3 cm/s to 100.5 cm/s with the supplementation of 1 g xanthan/l. Maximum specific product yield, namely 0.74 g polysaccharide/g biomass, was achieved with inlet air supply of 3% O2 and impeller tip speed of 100.5 cm/s.
The biological activities of polysaccharides specifically depend on the chemical structure, the size of the polysaccharide backbone, the structure of the side chain groups and the degree of branching. The β(1 → 3) backbone and the β(1 → 6) branch of polysaccharides are probably responsible for their anti-tumor activity. Variations of biological properties of polysaccharides usually follow from variations in microorganisms, the compositions of media and operational conditions. Polysaccharides isolated from Agaricus blazei have stronger anti-tumor activity against Sarcoma 180 in mice than those from Ganoderma lucidum, Lentiuu edodes, and Coriolus versicolor. Harvest time in a submerged culture determines the quality of the polysaccharide which is associated with the presence of glucanase in the broth. Conventional fermentation operational parameters may not reflect the biological quality of the polysaccharides due to the ambiguous correlations between the structures of polysaccharide and these parameters. Although an in vitro macrophage cell line may be used to monitor the biological quality of polysaccharides by measuring their ability to release cytokine, such a procedure usually takes at least 3 d. The observation presents a great need and challenge to monitor the biological quality of the anti-tumor polysaccharides in a submerged culture. Several reports have related the biological properties of polysaccharides to their molecular weights. Most have indicated that polysaccharides with high molecular weights have high biological properties; however, little attempt has been made to monitor the quality of polysaccharides in a submerged culture. The objective of this study is to develop a method for monitoring the quality of polysaccharides in a submerged culture.
Culture pH is one of the most important parameters affecting polysaccharide fermentations. However, inconsistent conclusions have been drawn in literatures that optimal polysaccharide formation occurred in higher culture pH, and in lower culture pH. Nevertheless, relatively little attention has been focused on culture pH on the biological activity of polysaccharides. Thus, the main objective of this study is to propose a fermentation process with high quality polysaccharides by investigating the influence of culture pH on the yield, molecular weight distribution,

關鍵字(中)

★ 巴西洋菇
★ 攪拌速度
★ 通氣
★ pH
★ 生物活性
★ 溫度
★ 多醣體

關鍵字(英)

★ protectants
★ polysaccharide
★ biological quality
★ Culture pH
★ Agaricus blazei Murill

論文目次

目錄
內容頁數
摘要………………………………………………………………………I
目錄…………………………………………………………………VII
圖目錄………………………………………………………………XIII
表目錄………………………………………………………………XVII
第一章、前言……………………………………………………………1
1.1 簡介……………………………………………………………1
1.2 文獻回顧……………………………………………………………5
1.2.1真菌多醣的介紹………………………………………………5
1.2.1.1真菌胞外多醣的合成…………………………………6
1.2.1.2菇類多醣抗腫瘤性…………………………………10
1.2.2免疫與抗癌…………………………………………………17
1.2.2.1免疫…………………………………………………17
1.2.2.2腫瘤與免疫系統……………………………………17
1.2.2.3生物反應修飾物質…………………………………18
1.2.2.3.1常用之生物反應修飾物質…………………18
1.2.2.4免疫活性物質之評估方法…………………………21
1.2.2.4.1免疫活性因子的評估………………………21
1.2.2.5 β-D-glucan的抗腫瘤機制…………………………24
1.2.2.6 β-D-glucan多醣體結構與活性的關係……………26
1.2.2.6.1多醣分子量分佈與活性的關係……………26
1.2.2.6.2 (1→3)鍵結的-β-D-葡聚醣主鏈與活性的關係…………………………………………27
1.2.2.6.3多醣分支度與活性的關係……………………28
1.2.2.6.4構形與活性的關係……………………………29
1.2.2.7 (1→3)-β-D-glucan測定……………………………30
1.2.2.7.1 Aniline blue的專一性……………………30
1.2.2.7.2 Aniline blue檢測法之建立………………30
1.2.3 巴西洋菇……………………………………………………32
1.2.3.1巴西洋菇由來與分類……………………………32
1.2.3.2巴西洋菇生長環境和培植方式…………………32
1.2.3.3巴西洋菇的化學成分……………………………33
1.2.3.4巴西洋菇的活性成分……………………………33
1.2.3.5巴西洋菇多醣體…………………………………35
1.2.3.5.1巴西洋菇多醣體之相關研究……………37
1.2.4 深層液態發酵培養…………………………………………40
1.2.4.1化學因素……………………………………………41
1.2.4.1.1培養基組成之碳源………………………41
1.2.4.1.2培養基組成之氮源………………………42
1.2.4.1.3培養基組成之碳氮比……………………42
1.2.4.1.4培養基組成之無基鹽類…………………43
1.2.4.2物理因子……………………………………………43
1.2.4.2.1剪切力……………………………………43
1.2.4.2.1.1攪拌速率與剪切力…………44
1.2.4.2.2 pH值………………………………………46
1.2.4.2.3溫度………………………………………47
1.2.4.2.4通氣………………………………………48
1.3 研究動機與本文大綱……………………………………………49
1.3.1研究動機……………………………………………………49
1.3.2本文大綱……………………………………………………51
第二章、材料與方法 ………………………………………………… 53
2.1 實驗材料…………………………………………………………53
2.1.1實驗菌株……………………………………………………53
2.1.2實驗藥品……………………………………………………53
2.1.3實驗儀器及其他設備………………………………………55
2.1.4實驗裝置……………………………………………………57
2.2 實驗方法…………………………………………………………58
2.2.1菌株保存……………………………………………………58
2.2.2培養基組成…………………………………………………58
2.2.3操作條件……………………………………………………59
2.2.4分析方法……………………………………………………60
2.3 巴西洋菇發酵液多醣體之生物活性測定………………………61
2.3.1 細胞激素測定………………………………………………61
2.3.1.1細胞株………………………………………………61
2.3.1.2細胞株保存…………………………………………62
2.3.1.3細胞株解凍…………………………………………62
2.3.1.4細胞株繼代培養……………………………………62
2.3.1.5細胞株培養液組成…………………………………62
2.3.1.6動物細胞激素測定實驗流程………………………63
2.3.2 發酵液抗腫瘤細胞生長活性測試…………………………64
2.3.2.1細胞株保存…………………………………………64
2.3.2.2細胞株解凍…………………………………………65
2.3.2.3細胞株繼代培養……………………………………65
2.3.2.4細胞株培養液組成…………………………………65
2.3.2.5發酵液抗腫瘤細胞生長活性實驗流程……………67
2.3.2.5.1發酵液抗腫瘤細胞液預培養…………….67
2.3.2.5.2抗腫瘤細胞生長活性實驗………………67
第三章、不同攪拌強度對巴西洋菇生產多醣之影響……………69
3.1 前言…………………………………………………………69
3.2 實驗方法…………………………………………………………78
3.2.1 菌株及培養基………………………………………………78
3.2.2 發酵操作條件……………………………………………78
3.3 結果與討論………………………………………………………79
3.3.1 攪拌器葉尖速度對細胞產率及比生長速率的影響…79
3.3.2攪拌器葉尖速度對產物產率及產物生產速率的影響…81
3.3.3添加0.1% xanthan對細胞生長及多醣代謝之影響………85
3.3.4 高攪拌器葉尖速度下不同含氧量空氣對細胞生長及多醣代謝之影響……………………………………………………89
3.3.5 攪拌器葉尖速度對巴西洋菇生產多醣生物活性之影響…91
3.3.6 不同反應器對細胞生長及細胞代謝多醣的影響…………99
3.3.6.1不同反應器對細胞生長的影響……………………99
3.3.6.2不同反應器對細胞代謝多醣的影響……………100
3.3.6. 不同反應器對巴西洋菇生產多醣生物活性之影響…………………………………………………102
3.4 巴西洋菇發酵液抗腫瘤能力測試……………………………104
3.5 結論………………………………………………………………107
第四章、不同空氣通氣量對巴西洋菇生產多醣之影響………108
4.1 前言………………………………………………………………108
4.2 實驗方法…………………………………………………………113
4.2.1 菌株及培養基……………………………………………113
4.2.2 發酵操作條件……………………………………………113
4.3 結果與討論………………………………………………………113
4.3.1 不同空氣通氣量對細胞生長的影響……………………113
4.3.2 不同空氣通氣量對細胞代謝多醣的影響………………114
4.3.3 不同空氣通氣量對多醣生物活性之影響………………115
4.4 結論…………………………………………………………119
第五章、溫度對巴西洋菇生產多醣之影響……………………120
5.1 前言……………………………………………………………120
5.2 實驗方法……………………………………………………123
5.2.1 菌株及培養基……………………………………………123
5.2.2 發酵條件…………………………………………………123
5.3 結果與討論………………………………………………………124
5.3.1 不同溫度對細胞生長的影響……………………………124
5.3.2 不同溫度對細胞代謝多醣之影響………………………124
5.3.3 不同溫度對巴西洋菇生產多醣生物活性之影響………126
5.4 結論………………………………………………………………129
第六章、不同起始pH值對巴西洋菇生產多醣之影響………………130
6.1 前言………………………………………………………………130
6.2 實驗方法…………………………………………………………138
6.2.1菌株及培養基………………………………………………138
6.2.2 操作條件…………………………………………………138
6.3 結果與討論………………………………………………………139
6.3.1不同起始pH值巴西洋菇細胞生長之影響………………139
6.3.2不同起始pH值巴西洋菇生長多醣之影響………………139
6.3.3不同起始pH值巴西洋菇多醣生物活性之影響…………141
6.4 結論………………………………………………………………144
第七章、總結論與建議………………………………………………145
7.1 總結………………………………………………………………145
7.2 建議………………………………………………………………146
參考文獻…………………………………………………………147

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指導教授

徐敬衡(Chin-Hang Shu)

審核日期

2004-7-18

推文