臺灣博碩士論文加值系統

本研究由腐壞水果、高雄區土壤、甘藷等來源中篩選得到 76 株微生物具有麩胱甘肽的產生能力，其中以台農10 號甘藷中分離得到的酵母菌 (Pichia kudriavzevii KR601) 產量最高。本論文以市售培養基 MEB 探討KR601 生產麩胱甘肽 (GSH) 的最適條件，說明如下:培養溫度及時間為35℃、24 小時，GSH 產量為21.32 ± 0.95 mg/L (以乾物重計為0.74%)；最適初始 pH 為4-6，GSH 產量為20.61-21.29mg/L (0.75%)；最適培養箱震盪速率為150-200 rpm，GSH 產量為22.62 ± 0.83 mg/L。各種打破微生物細胞壁的理化方法中，物理法以沸水處理4-10 分鐘時，破壁效果最好。化學法 (包括添加檸檬酸、氨水、酒精及乙酸乙酯等) 中，以 40% 酒精之破菌效果最好，比沸水破菌者 GSH 含量增加 16%。以葡萄糖、麥芽糖、蔗糖、果糖、半乳糖、甘油等為碳源，探討其對GSH 產量的影響，其中以葡萄糖的影響最大，葡萄糖之最適濃度為1%。KR601 無法利用無機氮源，如硫酸銨，醋酸銨，硝酸銨及尿素等；有機氮源部分以 Soya Petone 及 Malt Extract 的利用率最佳，其最適濃度分別為 1.5% 及 4%。甘胺酸及麩胺酸對 KR601 產生GSH 的影響不大。半胱胺酸則大幅提升 KR601 的 GSH 產生量，添加 0.25% 半胱胺酸時，GSH 的產生量提升約兩倍，GSH 濃度為72.33 ± 0.87 mg/L，占菌體乾重之 2.26%。饋料補糖 (1% 葡萄糖) 的批式發酵過程中，生物量及GSH 產生量各增加 32%；饋料補氮 (魚鱗水解液) 的批式發酵法中，提升其生物量及 GSH 產生量。饋料補 半胱胺酸 (0.25%) 的批式發酵法中，培養24 小時後，GSH 產生量為85.38 mg/L (以乾重計為2.75%)，為未添加半胱胺酸者之2.4 倍。

Seventy-six strains having glutathione (GSH) producing activity were isolated from peel of fruits, Kaohsiung area soil, potatoes, that strain from sweet potatoes named Pichia kudriavzevii KR601 showed the highest activity. The aim of this article is to study the optimal fermentation conditions for KR601 to produce GSH. The optimal conditions for KR601 to produce GSH are listed as follows (using commercial MEB media): incubation time & temperature, 35℃ for 24 hr, GSH yield 21.32 ± 0.95 mg/L (0.74% at dry base); initial pH 4-6, GSH yield 20.61-21.29 mg / L (0.75%); shaking rate 150-200 rpm, GSH yield 22.62 ± 0.83 mg / L. Physical and chemical methods of cell disruption to extract GSH from KR601 were then investigated. KR601 cell disrupted by boiling water for 4-10 minutes showed the highest efficiency in physical method. Citric acid, ammonia, alcohol and ethyl acetate were used as extraction solvent in chemical methods. Among them, extraction media of 40% alcohol showed the highest efficiency which is 16% higher than that of boiling water. Glucose, maltose, sucrose, fructose, galactose, glycerol were used as carbon sources to investigate their effects to KR601 on GSH production. Glucose showed the highest effect with optimum concentration at 1%. Inorganic nitrogen sources of ammonium sulfate, ammonium acetate, ammonium nitrate and urea were unable to be used by KR601. In nitrogen sources, soya petone and malt extract showed the highest effect to KR601 on GSH production with optimum concentration of 1.5% and 4%, respectively. Little effect was found in those adding with glutamate and glycine, however, possitive effect was found in that adding with cysteine. Adding 0.25% cysteine to the media of KR601 resulted with 2-folds increase on GSH concentration being 72.33 ± 0.87 mg/L (2.58% at dry base). In fed-batch fermentation of KR601 with additional 1% glucose added at 8h, biomass and GSH concentration increased by 32%, while only biomass increased when additional scale hydrolyzates was added at 8 h. However, if additional 0.25% cysteine was added at 8 h, GSH concentration reached 85.38 mg/L (2.75% at dry base) which is 2.4-folds compared with control.

摘要 I
Abstract III
誌謝 V
目錄 VI
表目綠 XI
圖目錄 XII
附圖目錄 XV
第一章 前言 1
一、 麩胱甘肽 (Glutathione, GSH) 3
1. 麩胱甘肽之進展 3
2. 麩胱甘肽之結構與特性 3
3. 麩胱甘肽之生理功能 4
4. 麩胱甘肽在工業上之應用 8
二、 麩胱甘肽之生產方法 10
1. 萃取法 10
2. 化學合成法 11
3. 生物合成法 11
三、 麩胱甘肽之萃取 19
1. 機械破碎法 20
2. 非機械式 21
四、 醱酵程序 23
第三章 材料與方法 25
一、材料 25
二、化學藥品: 26
三、儀器 28
四、實驗架構 29
五、方法 30
(二) 菌株之保存 30
(四) 分析菌數、生物量、GSH 產生量及 GSH 含量 . 31
(五) 菌體破碎 34
(六) 最適培養環境條件之探討 36
(七) 最適培養基配方之探討 38
(八) 麩胱甘肽的分離純化 40
1. 陽離子交換樹脂之預處理 40
2. 不同樹脂之靜態吸附效果 40
3. pH 值對樹脂靜態吸附之影響 41
4. 不同鹽濃度對於樹脂洗脫之影響 41
5. 樣品純化 41
6. HPLC 分析純化效果 42
(九) DNS 還原醣含量之測定 42
(十) 胜肽濃度測定 43
(十一) 批次與饋料發酵探討 44
(十二) 統計分析 46
第四章 結果與討論 47
壹、菌種篩選及鑑定 47
一、菌種篩選 47
二、菌種鑑定 47
貳、探討最適破菌條件 53
一、 沸水破菌最適時間 53
二、 微波、超音波、凍融法破壁之比較 53
三、 化學法破菌之最適條件探討 53
參、 探討KR601 菌株最適培養條件之探討 58
一、 KR601 菌株之生長曲線 58
二、 培養溫度之探討 58
三、 培養基初始 pH 值之探討 59
四、 震盪速率 (培養基溶氧) 之探討 59
肆、 最適培養基組成 66
一、 碳源種類碳討 66
二、 最適之葡萄糖濃度之探討 66
三、 氮源種類探討 67
四、 Soya peptone 濃度之探討 67
五、 微量元素之探討 68
六、 胺基酸前驅物添加之探討 68
七、 半胱胺酸濃度之探討 69
伍、 GSH 的分離及純化 77
一、 GSH 標準品與不同陽離子交換樹脂之吸附作用 77
二、 pH 值對陽離子交換樹脂吸附GSH 效果之影響 77
三、 不同鹽濃度對 GSH 的脫附效果 78
四、 KR601 發酵液 78
陸、 探討批式饋料發酵之條件 84
一、 發酵過程還原糖之變化 84
二、 批式饋料發酵 84
第五章 結論 91
第六章 參考文獻 94

王勝弘。2003。酵母菌所產葡萄糖耐量因子活性及其最佳生產條件之探討。國立台灣海洋大學食品科學系碩士學位論文，基隆。
李英漢。2012。魚鱗膠原蛋白胜肽之礦物質結合功能性探討。國立高雄海洋科技大學水產食品科學研究所碩士學位論文，高雄。
李鴻昌。2013。虱目魚魚鱗功能性胜肽之製備與純化及礦物質螯合能力探討。國立高雄海洋科技大學水產食品科學研究所碩士學位論文，高雄。
周佳棟、曹飛、張小龍、楊穎、應漢傑及韋萍。2009。Chinese Journalof Organic Chemistry。Vol. 29，No. 8, 1272～1277。
柯惠菁，2005。Meiothermus I40 菌株角蛋白酶產量最適化研究，國立高雄海洋科技大學水產食品科學系研究所碩士學位論文，高雄。
師紅、文瑞麗、馬清義、金學林、吳民耀。 (2010)。 哺乳動物精子冷凍的抗氧化研究進展. Chinese Bulletin of Life Sciences, 22(9)。
陳俊傑。2006。以 S. cerevisiae FC-3 批式生產γ-GC 與 GSH 之發酵動力學解析。國立雲林科技大學化學工程系碩士班碩士學位論文，雲林。
陳建誌。2011。鱸魚魚鱗膠原蛋白胜肽製備及功能性。國立高雄海洋科技大學水產食品科學研究所碩士學位論文，高雄。
陳堅、堵國成、衛功元及華兆哲。(2005)。微生物重要代謝產物-發酵生產與過程解析。工業化學出版社。北京。
黃富國。2005。酵母菌突變株 S. cerevisiae FC-3 生產 γ-GC 與 GSH之最適化及相關生合成酵素之基因選殖。國立雲林科技大學化學工程系碩士班碩士學位論文，雲林。
黃裕仁。2009。Vogesella sp.分泌之魚鱗水解酵素之特性及純化。國立高雄海洋科技大學水產食品科學研究所碩士學位論文，高雄。
衛功元、李寅、堵國成、陳堅一。(2003) 。Candida utilis 生物合成麩胱甘肽的營養及環境條件術. 應用與環境生物學報, 9(6), 642-646.
衛功元、李寅、堵國成。2003。溫度對谷胱甘肽分批發酵的影響及動力學模型們。生物工程學報。19(3)：358-363.
謝俊生。2002。台灣金線連抑制肝癌細胞生長抗氧化機制的探討。中國醫藥學院醫學研究所碩士論文。
鍾閔伃。2005。酵母菌菌體破碎方法及其葡萄糖耐量因數萃取物之安定性探討。國立台灣海洋大學食品科學系碩士學位論文，基隆。
魏崢、聶琰暉、劉樂庭、盧潔于、常海。 (2009)。多聚磷酸鹽在原核和真核生物中的研究進展。生理科學進展, 40(3), 197-202.
羅偉豪。2014。吳郭魚魚鱗功能性胜肽之製備與純化及礦物質螯合能力探討。國立高雄海洋科技大學水產食品科學研究所碩士學位論文，高雄。
黨建章、陳海宴、黎俊、黃錦珍、鍾承贊。2008。發酵技術概論。新文京開發出版。新北市。
Alfafara, C. G., Kanda, A., Shioi, T., Shimizu, H., Shioya, S and Suga, K. I. (1992). Effect of amino acids on glutathione production by Saccharomyces cerevisiae. Applied microbiology and biotechnology, 36(4), 538-540.
Amino acid content of foods and biological data on proteins, FAO, Rome, 1968.
Arrigo, A. P. (1999). Gene expression and the thiol redox state. Free Radical Biology and Medicine, 27(9), 936-944.
Bachhawat, A. K., Ganguli, D., Kaur, J., Kasturia, N., Thakur, A., Kaur, H., ... and Yadav, A. (2009). Glutathione production in yeast. In Yeast biotechnology: diversity and applications (pp. 259-280). Springer Netherlands.
Bibila, T. A and Robinson, D. K. (1995). In pursuit of the optimal fed-batch process for monoclonal antibody production. Biotechnology progress, 11(1), 1-13.
Boekhout, T and Kurtzman, C. P. (1996). Principles and methods used in yeast classification, and an overview of currently accepted yeast genera. InNonconventional Yeasts in Biotechnology (pp. 1-81). Springer Berlin Heidelberg.
Bosch-Morell, F., Sanz, A., Díaz-Llopis, M and Romero, F. J. (1996). Lipid peroxidation products in human subretinal fluid. Free Radical Biology and Medicine, 20(7), 899-903.
Brigham, K. L. (1991). Oxygen radicals—an important mediator of sepsis and septic shock. Klinische Wochenschrift, 69(21-23), 1004-1008.
Carlson, A., Signs, M., Liermann, L., Boor, R and Jem, K. J. (1995). Mechanical disruption of Escherichia coli for plasmid recovery. Biotechnology and bioengineering, 48(4), 303-315.
Carmel-Harel, O and Storz, G. (2000). Roles of the glutathione-and thioredoxin-dependent reduction systems in the Escherichia coli and Saccharomyces cerevisiae responses to oxidative stress. Annual Reviews in Microbiology,54(1), 439-461.
Cecchi, C., Latorraca, S., Sorbi, S., Iantomasi, T., Favilli, F., Vincenzini, M. T and Liguri, G. (1999). Gluthatione level is altered in lymphoblasts from patients with familial Alzheimer's disease. Neuroscience letters, 275(2), 152-154.
Cha, J. Y., Park, J. C., Jeon, B. S., Lee, Y. C and Cho, Y. S. (2004). Optimal fermentation conditions for enhanced glutathione production by Saccharomyces cerevisiae FF-8. JOURNAL OF MICROBIOLOGY-SEOUL-,42(1), 51-55.
Church, F. C., Swaisgood, H. E., Porter, D. H and Catignani, G. L. (1983). Spectrophotometric assay using o-phthaldialdehyde for determination of proteolysis in milk and isolated milk proteins. Journal of Dairy Science, 66(6), 1219-1227.
Clemens, M. R. (1991). Free radicals in chemical carcinogenesis. Klinische Wochenschrift, 69(21-23), 1123-1134.
Cook, J. R., Huang, D. P., Burkhardt, A. L., Goldman, M. E., Carroll, M., Bresnick, E and Chiu, J. F. (1984). Assessment of the anti-tumor potential of glutathione. Cancer letters, 21(3), 277-283.
Dannenmann, B., Lehle, S., Hildebrand, D. G., Kübler, A., Grondona, P., Schmid, V and Schulze-Osthoff, K. (2015). High glutathione and glutathione peroxidase-2 levels mediate cell-type-specific DNA damage protection in human induced pluripotent stem cells. Stem cell reports, 4(5), 886-898.
Dolphin, D., Poulson, R and Avramović, O. (1989). Glutathione: chemical, biochemical, and medical aspects. John Wiley & Sons Inc.
Dringen, R., Gutterer, J. M and Hirrlinger, J. (2000). Glutathione metabolism in brain. European Journal of Biochemistry, 267(16), 4912-4916.
Dröge, W., Schulze-Osthoff, K. L. A. U. S., Mihm, S., Galter, D., Schenk, H. E., Eck, H. P., ... and Gmünder, H. (1994). Functions of glutathione and glutathione disulfide in immunology and immunopathology. The FASEB journal,8(14), 1131-1138.
DU, W. G. Y. L. Y and Jian, G. C. C. (2003). Kinetic Models for the Effect of Temperature on Batch Glutathione Fermentation by Candida utilis [J]. Chinese Journal of Biotechnology, 3, 022.
Fell, J. W and Kurtzman, C. P. (Eds.). (1998). The Yeasts; a Taxonomic Study. Elsevier.
Forman, H. J., Zhang, H and Rinna, A. (2009). Glutathione: overview of its protective roles, measurement, and biosynthesis. Molecular aspects of medicine, 30(1), 1-12.
Fraternale, A., Casabianca, A., Orlandi, C., Cerasi, A., Chiarantini, L., Brandi, G and Magnani, M. (2002). Macrophage protection by addition of glutathione (GSH)-loaded erythrocytes to AZT and DDI in a murine AIDS model. Antiviral research, 56(3), 263-272.
Freimund, S., Sauter, M., Käppeli, O and Dutler, H. (2003). A new non-degrading isolation process for 1, 3-β-D-glucan of high purity from baker's yeast Saccharomyces cerevisiae. Carbohydrate Polymers, 54(2), 159-171.
Generally, G. S. H. (1997). Multiple roles of glutathione in the central nervous system. Biol. Chem, 378, 793-802.
Gotoh, T and Kikuchi, K. I. (2000). Contamination of an anion-exchange membrane by glutathione. Bioseparation, 9(1), 37-41.
Greppi, A., Krych, Ł., Costantini, A., Rantsiou, K., Hounhouigan, D. J.,
Arneborg, N., ... and Jespersen, L. (2015). Phytase-producing capacity of yeasts isolated from traditional African fermented food products and PHYPk gene expression of Pichia kudriavzevii strains. International journal of food microbiology, 205, 81-89.
Harington, C. R and Mead, T. H. (1935). Synthesis of glutathione. Biochemical Journal, 29(7), 1602.
Hayes, J. D and McLELLAN, L. I. (1999). Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress. Free radical research, 31(4), 273-300.
Hopkins, F. G and Dixon, M. (1922). On glutathione II. A thermostable oxidation-reduction system. Journal of Biological Chemistry, 54(3), 527-563.
Huang, W. H., Shieh, G. S and Wang, F. S. (2010). RuntoRun Optimization of FedBatch Fermentation for Ethanol Production. Chemical Engineering & Technology, 33(9), 1488-1494.
Jones, D. P. (2006). Redefining oxidative stress. Antioxidants & redox signaling, 8(9-10), 1865-1879.
Katrusiak, A. E., Paterson, P. G., Kamencic, H., Shoker, A and Lyon, A. W. (2001). Pre-column derivatization high-performance liquid chromatographic method for determination of cysteine, cysteinyl–glycine, homocysteine and glutathione in plasma and cell extracts. Journal of Chromatography B: Biomedical Sciences and Applications, 758(2), 207-212.
Knapen, M. F., Zusterzeel, P. L., Peters, W. H and Steegers, E. A. (1999). Glutathione and glutathione-related enzymes in reproduction: a review.European Journal of Obstetrics & Gynecology and Reproductive Biology, 82(2), 171-184.
Kugiyama, K., Ohgushi, M., Motoyama, T., Hirashima, O., Soejima, H., Misumi, K., ... and Yasue, H. (1998). Intracoronary infusion of reduced glutathione improves endothelial vasomotor response to acetylcholine in human coronary circulation. Circulation, 97(23), 2299-2301.
Lee, J., Lee, S. Y., Park, S and Middelberg, A. P. (1999). Control of fed-batch fermentations. Biotechnology advances, 17(1), 29-48.
Li, C., Yu, J., Wang, D., Li, L., Yang, X., Ma, H and Xu, Y. (2016). Efficient removal of zinc by multi-stress-tolerant yeast Pichia kudriavzevii A16.Bioresource technology, 206, 43-49.
Li, W., Li, Z and Ye, Q. (2010). Enzymatic synthesis of glutathione using yeast cells in two-stage reaction. Bioprocess and biosystems engineering, 33(6), 675-682.
Li, Y., Wei, G and Chen, J. (2004). Glutathione: a review on biotechnological production. Applied microbiology and biotechnology, 66(3), 233-242.
Liang, G. B., Du, G. C and Chen, J. (2008). A novel strategy of enhanced glutathione production in high cell density cultivation of Candida utilis—cysteine addition combined with dissolved oxygen controlling. Enzyme and Microbial Technology, 42(3), 284-289.
Liang, G., Liao, X., Du, G and Chen, J. (2008). Elevated glutathione production by adding precursor amino acids coupled with ATP in high cell density cultivation of Candida utilis. Journal of applied microbiology, 105(5), 1432-1440.
Liang, G., Liao, X., Du, G and Chen, J. (2009). A new strategy to enhance glutathione production by multiple H 2 O 2-induced oxidative stresses in Candida utilis. Bioresource technology, 100(1), 350-355.
Liang, G., Wang, B., Xie, J and Mo, Y. (2009). Novel pH control strategy for glutathione overproduction in batch cultivation of Candida utilis. African Journal of Biotechnology, 8(22).
Lindsay, J., Metcalf, J. S and Codd, G. A. (2006). Protection against the toxicity of microcystin-LR and cylindrospermopsin in Artemia salina and Daphnia spp. by pre-treatment with cyanobacterial lipopolysaccharide (LPS). Toxicon, 48(8), 995-1001.
Liu, C. H., Hwang, C. F and Liao, C. C. (1999). Medium optimization for glutathione production by Saccharomyces cerevisiae. Process Biochemistry,34(1), 17-23.
Lu, F., Wang, Y., Bai, D and Du, L. (2005). Adaptive response of Saccharomyces cerevisiae to hyperosmotic and oxidative stress. Process Biochemistry, 40(11), 3614-3618.
Lu, S. C. (2013). Glutathione synthesis. Biochimica et Biophysica Acta, 1830(5), 3143-3153.
Meister, A. (1988). Glutathione metabolism and its selective modification. J Biol Chem, 263(33), 17205-17208.
Meister, A. (1994). Glutathione-ascorbic acid antioxidant system in animals.Journal of Biological Chemistry-Paper Edition, 269(13), 9397-9400.
Meister, A. M. E. A and Anderson, M. E. (1983). Glutathione. Annual review of biochemistry, 52(1), 711-760.
Miller, G. L. (1959). Use of dinitrosalicylic acid reagent for determination of reducing sugar. Analytical chemistry, 31(3), 426-428.
Minihane, B. J and Brown, D. E. (1986). Fed-batch culture technology.Biotechnology advances, 4(2), 207-218.
Monje-Casas, F., MICHáN, C and Pueyo, C. (2004). Absolute transcript levels of thioredoxin-and glutathione-dependent redox systems in Saccharomyces cerevisiae: response to stress and modulation with growth. Biochemical Journal, 383(1), 139-147.
Monostori, P., Wittmann, G., Karg, E and Túri, S. (2009). Determination of glutathione and glutathione disulfide in biological samples: An in-depth review.Journal of Chromatography B, 877(28), 3331-3346.
Moron, M. S., Depierre, J. W and Mannervik, B. (1979). Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochimica et Biophysica Acta (BBA)-General Subjects, 582(1), 67-78.
Nandi, L. Y. C. J. Z and Shiyi, F. W. R. W. L. (1998). The Effect of Environmental Conditions and Glucose Feeding Strategy on Glutathione (GSH) Production [J]. CHINESE JOURNAL OF BIOTECHNOLOGY, 2.
Ogunremi, O. R., Agrawal, R and Sanni, A. I. (2015a). Development of
Cerealbased functional food using cerealmix substrate fermented with probiotic strain–Pichia kudriavzevii OG32. Food science & nutrition, 3(6), 486-494.
Ogunremi, O. R., Sanni, A. I and Agrawal, R. (2015b). Hypolipidaemic and antioxidant effects of functional cereal-mix produced with probiotic yeast in rats fed high cholesterol diet. Journal of Functional Foods, 17, 742-748.
Ohtake, Y., Watanabe, K., Tezuka, H., Ogata, T., Yabuuchi, S., Murata, K and Kimura, A. (1988). The expression of the γ-glutamylcysteine synthetase gene of Escherichia coli B in Saccharomyces cerevisiae. Agricultural and biological chemistry, 52(11), 2753-2762.
Pastore, A., Federici, G., Bertini, E and Piemonte, F. (2003). Analysis of glutathione: implication in redox and detoxification. Clinica chimica acta,333(1), 19-39.
Penninckx, M. (2000). A short review on the role of glutathione in the response of yeasts to nutritional, environmental, and oxidative stresses. Enzyme and microbial technology, 26(9), 737-742.
Penninckx, M. J. (2002). An overview on glutathione in Saccharomyces versus non-conventional yeasts. FEMS yeast research, 2(3), 295-305.
Prasad, K., Kalra, J and Bharadwaj, L. (1993). Cardiac depressant effects of oxygen free radicals. Angiology, 44(4), 257-270.
Ramassamy, C., Averill, D., Beffert, U., Theroux, L., Lussier-Cacan, S., Cohn, J. S., ... and Poirier, J. (2000). Oxidative insults are associated with apolipoprotein E genotype in Alzheimer's disease brain. Neurobiology of disease, 7(1), 23-37.
Rollini, M and Manzoni, M. (2006). Influence of different fermentation parameters on glutathione volumetric productivity by Saccharomyces cerevisiae. Process Biochemistry, 41(7), 1501-1505.
Rollini, M., Musatti, A and Manzoni, M. (2010). Production of glutathione in extracellular form by Saccharomyces cerevisiae. Process Biochemistry, 45(4), 441-445.
Saka, S., Aouacheri, W and Abdennour, C. (2002). The capacity of glutathione reductase in cell protection from the toxic effect of heated oils. Biochimie,84(7), 661-665.
Samiec, P. S., Drews-Botsch, C., Flagg, E. W., Kurtz, J. C., Sternberg, P., Reed, R. L and Jones, D. P. (1998). Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes. Free Radical Biology and Medicine, 24(5), 699-704.
Sankh, S., Thiru, M., Saran, S and Rangaswamy, V. (2013). Biodiesel production from a newly isolated Pichia kudriavzevii strain. Fuel, 106, 690-696.
Scandalios, J. G. (1993). Oxygen stress and superoxide dismutases. Plant physiology, 101(1), 7.
Schieber, M and Chandel, N. S. (2014). ROS function in redox signaling and oxidative stress. Current Biology, 24(10), R453-R462.
Slaughter, J. C and Nomura, T. (1992). Autocatalytic degradation of proteins in extracts of a brewing strain of Saccharomyces cerevisiae. The role of endoproteinases and exopeptidases. Applied microbiology and biotechnology,37(5), 638-642.
Stephen, D. W and Jamieson, D. J. (1997). Amino aciddependent regulation of the Saccharomyces cerevisiae GSH1 gene by hydrogen peroxide. Molecular microbiology, 23(2), 203-210.
Stipanuk, M. H. (2004). Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine. Annu. Rev. Nutr., 24, 539-577.
Suslick, K. S., Hyeon, T and Fang, M. (1996). Nanostructured materials generated by high-intensity ultrasound: sonochemical synthesis and catalytic studies. Chemistry of materials, 8(8), 2172-2179.
Thompson, A. B., Robbins, R. A., Romberger, D. J., Sisson, J. H., Teschler, H and Rennard, S. I. (1995). Immunological functions of the pulmonary epithelium. European Respiratory Journal, 8(1), 127-149.
Tietze, F. (1969). Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Analytical biochemistry, 27(3), 502-522.
Udeh, K. O., & Achremowicz, B. (1997). High-glutathione containing yeast Saccharomyces cerevisiae: optimization of production. Acta Microbiologica Polonica, 46(1), 105-114.
Ueda, Y., Yonemitsu, M., Tsubuku, T., Sakaguchi, M and Miyajima, R. (1997). Flavor characteristics of glutathione in raw and cooked foodstuffs. Bioscience, biotechnology, and biochemistry, 61(12), 1977-1980.
Vanessa Fiorentino, T., Prioletta, A., Zuo, P and Folli, F. (2013). Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Current pharmaceutical design, 19(32), 5695-5703.
Walling, C. (1982). The nature of the primary oxidants in oxidations mediated by metal ions. Oxidases and related redox systems, 85-97.
Wang, J., Wang, K., Wang, Y., Lin, S., Zhao, P and Jones, G. (2014). A novel application of pulsed electric field (PEF) processing for improving glutathione (GSH) antioxidant activity. Food chemistry, 161, 361-366.
Wang, M., Sun, J., Xue, F., Shang, F., Wang, Z and Tan, T. (2012). The effect of intracellular amino acids on gsh production by high-cell-density cultivation of Saccharomyces cerevisiae. Applied biochemistry and biotechnology, 168(1), 198-205.
Wen, S., Zhang, T and Tan, T. (2005). Optimization of the amino acid composition in glutathione fermentation. Process Biochemistry, 40(11), 3474-3479.
Wen, S., Zhang, T and Tan, T. (2006). Maximizing production of glutathione by amino acid modulation and high-cell-density fed-batch culture of Saccharomyces cerevisiae. Process Biochemistry, 41(12), 2424-2428.
Wierzbicka, G. T., Hagen, T. M and Tones, D. P. (1989). Glutathione in food.Journal of Food Composition and Analysis, 2(4), 327-337.
Winter, G., Cordente, A. G and Curtin, C. (2014). Formation of hydrogen sulfide from cysteine in Saccharomyces cerevisiae BY4742: genome wide screen reveals a central role of the vacuole. PloS one, 9(12), e113869.
Winterbourn, C. C. (1993). Superoxide as an intracellular radical sink. Free Radical Biology and Medicine, 14(1), 85-90.
Xiong, Z. Q., Guo, M. J., Guo, Y. X., Chu, J., Zhuang, Y. P., Wang, N. S and Zhang, S. L. (2010). RQ feedback control for simultaneous improvement of GSH yield and GSH content in Saccharomyces cerevisiae T65. Enzyme and Microbial Technology, 46(7), 598-602.
Xiong, Z. Q., Tu, X. R and Tu, G. Q. (2008). Optimization of medium
composition for actinomycin X2 production by Streptomyces spp JAU4234 using response surface methodology. Journal of industrial microbiology & biotechnology, 35(7), 729-734.
Zhang, T., Wen, S and Tan, T. (2007). Optimization of the medium for glutathione production in Saccharomyces cerevisiae. Process biochemistry,42(3), 454-458.