Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/56498
標題: 高經濟價值多元不飽和脂肪酸在菌藻類中之研發
Research and Development of High-Valued Polyunsaturated Fatty Acids in Fungi and Algae
作者: 黃永勝
關鍵字: 基礎醫學類, 食品科技;技術發展;omega-3;omega-3;omega-6 多元不飽和脂肪酸;gamma-次亞麻油酸;花生四烯酸;二十碳五烯酸;二十二碳六烯酸;魚油;菌藻類;培養與發酵;基因轉植技術;omega-6 polyunsaturated fatty acids;gamma-linolenic acid (GLA);arachidonic acid (ARA),eicosapentaenoic acid (EPA);docosahexaenoic acid (DHA);fish oil;fungi and algae;culture andfermentation;transgenic technique.
摘要: 
多元不飽和脂肪酸與人體健康有密切的關係。它們是細胞膜的主要成份,其存在影響細胞膜的流質狀態、電解物及養分之傳送,以及荷爾蒙與免疫等之活性與作用。有些多元不飽和脂肪酸也是eicosanoid (例如前列腺素、血栓素、白三烯素等) 的前質體(precursor)。這些eicosanoids 可調節全身細胞一切之生理作用。雖然多元不飽和脂肪酸在人體內可由必需脂肪酸,亞麻油酸(linoleic acid; LA) 及alpha-次亞麻油酸(脈-linolenic acid; ALA) 合成,但是,一般人體內合成的能力相當低,尤其易受食物與體內荷爾蒙,生理及病理狀況之影響,減低多元不飽和脂肪酸之合成。很多慢性疾病之發作也常和多元不飽和脂肪酸的不足有關。例如Gamma-次亞麻油酸(訕-linolenic acid; GLA) 是屬於omega-6 多元不飽和脂肪酸系列中的一個高經濟價值脂肪酸。於生物體內的omega-6 脂肪酸代謝過程中,GLA 以亞麻油酸(LA) 經第六去飽和.(島6-desaturase) 作用後而產生。根據細胞培養、動物與人體的實驗證明,GLA有調節免疫反應。同時亦對慢性疾病,包括風濕性關節炎、高血壓、脂肪過高…等,都有明顯的改善。花生四烯酸(Arachidonic acid, ARA) 也屬於omega-6 多元不飽和脂肪酸之系列。目前市面上之ARA 油主要是做為嬰兒奶粉中之添加物,具有增強嬰兒正常發育之功效。二十碳五烯酸(eicosapentaenoic acid, EPA) 與二十二碳六烯酸(docosahexaenoic acid, DHA)皆屬omega-3 多元不飽和脂肪酸。近年來之臨床實驗結果顯示EPA 具有降脂、消炎、降血栓等有益健康之療效。DHA 是腦、神經、視網膜之主要成分。初生嬰兒發育時期極需DHA,添加DHA 於嬰兒奶粉中有助嬰兒(尤其是早產嬰兒) 視覺及智力之發展。最新臨床結果亦證實經常食用DHA 可顯著的降低阿茲海默氏症(Alzheimer』s disease)及憂鬱症(depression) 之罹患機率。GLA 的主要來源自植物種子中提煉萃取(包括琉璃苣、月見草與黑醋栗) 或經由微生物(例如真菌)發酵而來。但是,原料取得不易、生產與純化成本相當高。即便是經由選種和改良種植的條件,可增加的程度仍然有限,加上於食用中以不常用菌類萃取之物,安全上的考量,是目前要全面推廣由真菌來產製GLA 作為營養補充品,是非常拮据的。ARA 主要來源為Mortierella alpina 菌屬。因美國Martek 公司擁有使用所有由菌類萃取之ARA 油的專利權,持續壟斷國際市場,市價一直偏高。另外,二十碳五烯酸(eicosapentaenoic acid, EPA)及二十二碳六烯酸(docosahexaenoic acid, DHA),皆屬於omega-3 多元不飽和脂肪酸,它們主要來自深海魚油。但由於過度捕魚,近年來漁獲漸顯拮据,往後魚油將不敷市場之需求。最近的資料顯示,市面上之魚油常含有污染物,重金屬及毒素。加上國人中有對魚類過敏的,或者因素食之關係,而無法食用這些來自魚的omega-3 多元不飽和脂肪酸。這些因素使得尋求新的非動物性omega-3 多元不飽和脂肪酸來源,變成一種必要的趨勢。目前國內對上述高經濟價值脂肪酸之需求主要仰賴進口。由於價格昂貴,限制了這些高價多元不飽和脂肪酸之廣泛使用。在本計劃中,我們將結合分子生物、發酵與油脂生化技術來研發一個創新與特殊的方法,用以製造高經濟價值之油脂。本計劃將分成三個階段來進行:首先,建立一個油脂化學分析研究室,具有完整性的設備,對各種不同油脂及脂溶性化合物能作定性與定量之分析。同時也要設立一個小型培養室,具備培養各種菌藻類之設施。其次,利用化學分析之方式來篩選適當之菌藻類,經由改良培養及發酵技術,增進高價油脂之產量。同時,利用定位轉酯(stereospecific transesterification)之技術,轉變在高經濟價值油中三酸甘油酯之分子結構,使多元不飽和脂肪酸易被小腸消化與吸收。第三階段則是利用分生技術,將從Mortierella alpina 或其他真菌類得來的島6-desaturase 基因植入非傳統酵母菌Yarrowia lipolytica。讓Y. lipolytica 轉形菌株能直接使用培養基中含有之碳源來大量生產GLA的高經濟價值油脂。同樣的,利用分子生物技術,也可將從其他菌藻類分離出的島17desatruase 基因植入M. alpina 內。讓M. alpina 轉型菌株也能大量生產EPA。這部份的實驗擬與益生生技公司合作,借用他們在酵母菌遺傳工程上的專長與經驗,以非傳統酵母菌及其他適當之菌藻類作為實驗材料,並利用分子生物技術,篩選出能大量生產GLA 及EPA 的轉型菌株,來進行高價油脂的製造與生產,進而提昇這些高價油脂在國內外的價值與應用。

Polyunsaturated fatty acids (PUFAs) are important for human health. They constitute theessential components of cell membranes, where they affect the membrane functions, such as fluidity,electrolyte transport and hormonal and immunological activities. They also serve as the precursor foreicosanoids (e.g., protstaglandinds, thromobxanes, and leukotrienes). These eicosanoids are moleculesthat regulate critical biological functions in cells. Although PUFAs can be synthesized from the parentessential fatty acids, linoleic acid (LA) and 脈-linolenic acid (ALA), but the overall capacity of humansto synthesize these PUFAs are rather low. The enzymes responsible for synthesis of these PUFAs arereadily modulated by dietary and hormonal factors. It has been demonstrated that low PUFA levels areassociated with the risk of many chronic degenerative diseases.訕-Linolenic acid (GLA) is a valued n-6 PUFA. It is originally metabolized from linoleic acid (LA)by the action of 島6-desaturase. Results from cell culture, animal models and human subjects haveshown that GLA exerts various beneficial effects on immune function and many chronic degenerativediseases, such as rheumatoid arthritis, high blood pressure, hyperlipidemia, etc. Arachidonic acid(ARA) is also a member of omega-6 PUFAs. Currently, ARA is used mainly as the supplement toinfant formula. It has been shown that ARA may affect the normal growth of human infants.Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are both omega-3 PUFAs. Recentclinical evidence has demonstrated that EPA can lower triglycerides in blood, reduce inflammation andthrombosis and many other beneficial effects. DHA is an important membrane constituent in brain,nervous system and retina. Supplementation of DHA in infant formula has been shown to improvevisual acuity and cognitive development. Most recently, consumption of DHA has been shown tosignificantly reduce the risk of Alzheimer disease and depression.To date, the sources of GLA are oils predominantly from small plant seeds such as borage,evening primrose, black currant, and to a small extent from microorganisms, such as Mucor. However,due to high fluctuations in availability, production/purification costs, and safety concerns of usingfungal oils, these existing GLA sources are expensive and not ideal for dietary supplementation. Themain source of ARA in market is from Mortierella alpina. However, Martek Inc. possesses patents ofusing the fungal ARA oils for different functions, they monopolize the world-wide market. The marketprice of fungal ARA oil is rather high. EPA and DHA are omega-3 PUFAs derived from marine fish oil.Due to overfishing in recent years, the fish stock becomes depleted. In future, the supply of fish oilwill not meet the market demands. Recent evidence shows that oils derived from fish are oftencontaminated with pollutants, heavy metals and toxins. More, some people are allergic to fish, andvegetarians do not eat fish. All these factors prompt the search for alternative sources of these omega-3PUFAs.In Taiwan, all these high-value PUFAs are imported. The high cost also greatly limits their wideruse for many beneficial effects. In this study, we plan to develop new and unique methods tosynthesize inexpensive high-value PUFA-containing oils. Our approach can be divided into 3 mainsteps. First, we plan to establish a well-equipped lipid chemistry analytical laboratory which is capableof analyzing different lipids and lipid-soluble chemicals. We also plan to establish a marinemicroorganism culture laboratory which is capable of culturing different marine fungi and algae. Next,we plan to utilize the above facilities to screen different microorganisms,and select the appropriatecandidates that are required for this study. In order to increase the yield of high-value PUFAs (such asARA and DHA), we plan to optimize the culture and fermentation procedures. To improve thedigestion and absorption of these high-value PUFAs oils, we also plan to modify the triacylglycerolmolecular structures in these oils through stereospecific trans-esterification and fractionationdistillation. The third part of this study involves in several disciplines including molecular biology,fermentation and lipid biochemistry techniques. We plan to construct a particular plasmid with acloned 島6-desaturase gene洶from M. alpina or other fungal sources and introduce it into Yarrowialipolytica, a strain of non-conventional but edible yeast. This approach is based on the fact that thisyeast can produce oil containing LA (the precursor of GLA) directly from carbon sources in medium.With a successful expression of the 島6-desaturase gene, the transformed yeast is capable of convertingLA to GLA. Similarly, we plan to isolate the 島17-desaturase (convert ARA to EPA) gene from othermicroorganisms, and transplant this gene to M. alpina. The expression of this gene will allow thistransformed microorganism to synthesize EPA from ARA. This part of study will be in collaborationwith Yeastern Biotech, Inc., a biotech company specialized in genetic engineering on yeast. Throughthis collaboration, we should be able to select the transformed fungi (or algae) that are capable ofproducing large quantities of high value-PUFAs (i.e., GLA and EPA), and promote the wider use ofthese oils for human health.
URI: http://hdl.handle.net/11455/56498
其他識別: NSC95-2320-B005-013-MY3
Appears in Collections:食品暨應用生物科技學系

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