臺灣博碩士論文加值系統

Coenzyme Q10 (CoQ10)被用來治療心臟疾病及高血壓，增強免疫系統，有益於過敏,哮喘及呼吸疾病的患者，同時也用來治療精神分裂、阿滋海默症、延緩帕金森氏症。
日本學者研究顯示CoQ10能保護胃及十二指腸的內壁，有助於十二指腸潰瘍的治療，激發及增強免疫系統的能力，比維他命E高40倍的作用，使得近來受到許多的注意。
光合菌中的Rhodobacter sphaeroides 具有生產CoQ10 的能力，本研究即以不同的碳氮源比例及生長條件對光合菌生產CoQ10 加以探討。研究結果顯示，搖瓶實驗中，以glucose為碳源，在單一氮源中，以濃度15g/L 的yeast extract (重量比為1:6)，其CoQ10生產率9.46 mg /L 為最高；而以濃度20g/L 的peptone (重量比為1:8)，其CoQ10生產率次之，為7.53 mg /L。在複合氮源方面，無機鹽類硫酸銨的添加有助於提高CoQ10生產率，其中以peptone 20 g/L (重量比為1:8)添加硫酸銨10g/L的CoQ10生產率提升較高，可達產率為7.84 mg/L。
在10公升發酵槽部份，在peptone 濃度為20g/L 時(重量比為1：8)，高濃度硫酸銨有利於產物生成，其CoQ10生產率最高為10mg /L 以上，可達到試量產量化生產的經濟效益。

Coenzyme Q10 (CoQ10) is a component of the respiratory chain with antioxidant property and it has been proposed as an agent for treating heart disease , hypertension and strengthening the immune system in recent years. It is good for patients with allergy, asthma, or other respiratory diseases. Besides, it can be clinically used to manage chronic schizophrenia, Alzheimer’s disease and Parkinson’s disease. According to the previous studies in Japan, CoQ10 can protect the mucosa of the stomach and the duodenum and that it maybe helpful to treat peptic ulcer diseases. It also can strengthen our immune system that is more powerful than Vitamin E for forty times. CoQ10 really attracts many people’s attention recently.
Rhodobacter sphaeroides is a species of photosynthetic bacteria ( PSB ) that has the ability to produce CoQ10. In this study, we used different sources with different proportion of carbon and nitrogen and created different growth conditions for this photosynthetic bacterium to produce CoQ10. Our study result showed that; in an experiment of shaking bottle, the production rate of CoQ10 was highest ( 9.46 mg/L) in the glucose-based carbon source and 15g/L of single nitrogen-yeast extract ( weight ratio=1:6). The production rate of CoQ10 was second ( 7.53 mg/L) in the 20g/L of peptone(weight ratio =1:8). In complex nitrogen sources, addition of inorganic ammonium sulfate was helpful to increase the production rate of CoQ10. We found that the production rate of CoQ10 increased more when we added inorganic ammonium sulfate into the solution of 20g/L of peptone(weight ratio =1:8) and its productive vales was 7.84 mg/L.
In a 10L fermented tank with the solution of 20g/L of peptone(weight ratio =1:8), high-concentration of ammonium sulfate was helpful for producing CoQ10 and its productive rate may be more than 10mg/L. The result meant that it can reach the economic benefits of large-scale production.

目錄
摘要....................…………………..……………..............................................................IV
英文摘要……………………………………………………………………………….....V
誌謝………………………………………………………………………………....……VI
目錄..........…......................……………........................................................................... VIII
圖目錄...............................................……………............................................................ XII
表目錄...............................................……………............................................................ XIV
第一章 緒論.............................................…………………….……............................... 1
1.1. 研究動機與背景..............…………..………….….........................................1
1.2. 研究目的..............................................................………….…………….......6
第二章 文獻回顧..........................................................................……………................9
2.1. 光合菌簡介與應用....................................................................……….….....9
2.2. CoQ10 的介紹.......................................................................………………...12
2.2.1. CoQ10 的發現...............................................................………………..12
2.2.2. 導致CoQ10 缺乏的原因......................................…………………......13
2.2.3. CoQ10 的作用..........................................................…..…………….....14
2.3. ubiquinone (CoQ10 )的合成..............................................................................15
2.4. CoQ10 的生產方式與影響因子..........................……………....................... 17
2.4.1. CoQ10 的生產方式.............................................……………..…..........17
2.4.1.1.生物萃取法………………………………………………………17
2.4.1.2.化學合成法……………………………………..………………..19
2.4.1.3.半化學合成法………………………………………..…………..19
2.4.1.4.微生物發酵法……………………………………………..…..…20
2.4.2. 影響CoQ10 產量的因子.........................................................................21
2.4.2.1. 添加營養素的影響......................................................................22
2.4.2.2. 添加金屬離子的影響..................................................................22
2.4.2.3. 添加胺基酸的影響......................................................................22
2.4.2.4. 碳氮比的影響..............................................................................22
2.4.2.5. 添加其他物質和照光條件的影響..............................................23
2.5. CoQ10 的市況簡介…………………………………………………………...27
2.6. CoQ10 的專利調查………….……………………………………………..…28
2.6.1.台灣專利……………………………………………….…………….….28
2.6.2.世界專利………………………………………………….………….….29
第三章實驗材料與方法................................................................................................... 32
3.1. 實驗流程......................................................................................................... 32
3.2. 實驗材料......................................................................................................... 32
3.2.1. 實驗菌株................................................................................................ 32
3.2.2. 實驗藥品................................................................................................ 33
3.2.3. 實驗儀器與設備.................................................................................... 34
3.3. 實驗方法......................................................................................................... 37
3.3.1. 菌種之活化............................................................................................ 37
3.3.2. 菌種保存................................................................................................ 37
3.3.3. 菌種特性之探討.................................................................................... 38
3.3.4. 種瓶之製備............................................................................................ 38
3.3.5. 碳氮比之計算........................................................................................ 38
3.3.6. 平板培養基............................................................................................ 38
3.3.7. 種瓶培養基............................................................................................ 39
3.3.8. 發酵槽培養基........................................................................................ 39
3.3.9. 生長曲線的測定.................................................................................... 40
3.3.10. 糖類(葡萄糖、果糖、蔗糖)的分析................................................... 40
3.3.11. CoQ10 的分析...................................................................................... 40
3.3.11.1. CoQ10 的檢量線建立............................................................... 40
3.3.11.2. CoQ10 含量的分析................................................................... 42
3.3.12. 氨離子濃度分析.................................................................................. 42
3.3.12.1.Bolleter 分析方法.......................................................................42
3.3.12.2.自動滴定儀分析方法..................................................................43
3.4. 搖瓶實驗..........................................................................................................44
3.4.1.添加金屬離子試驗...................................................................................44
3.4.2.碳源試驗...................................................................................................45
3.4.2.1. 以glucose 為主要碳源................................................................45
3.4.2.2. 以fructose 為主要碳源...............................................................45
3.4.2.3. 以sucrose為主要碳源..................................................................45
3.4.3. 氮源試驗.................................................................................................46
3.4.3.1. 以yeast extract 為主要氮源........................................................46
3.4.3.2. 以peptone 為主要氮源............................................................... 46
3.4.3.3. 以硫酸銨為主要氮源..................................................................46
3.4.4. 複合氮源－硫酸銨的影響.....................................................................46
3.5. 發酵槽實驗......................................................................................................47
第四章實驗結果與討論................................................................................................... 48
4.1. 搖瓶實驗......................................................................................................... 48
4.1.1. 添加金屬離子試驗.................................................................................48
4.1.2. 單一碳源－不同碳氮比........................................................................ 50
4.1.2.1. 不同sucrose 濃度的影響........................................................... 50
4.1.2.2. 不同fructose 濃度的影響.......................................................... 51
4.1.2.3. 不同glucose濃度的影響............................................................. 53
4.1.3. 單一氮源－不同碳氮比........................................................................ 55
4.1.3.1. 不同yeast extract 濃度的影響....................................................55
4.1.3.2. 不同peptone 濃度的影響........................................................... 56
4.1.3.3. 不同硫酸銨濃度的影響............................................................. 58
4.1.4. 複合氮源－硫酸銨的影響.................................................................... 59
4.1.4.1. 在固定yeast extract 濃度下，添加不同濃度硫酸銨的影響... 59
4.1.4.2. 在固定peptone 濃度下，添加不同濃度硫酸銨的影響............61
4.1.5. 單一氮源與複合氮源的比較................................................................ 62
4.2. 發酵槽實驗..................................................................................................... 65
4.2.1. 在固定硫酸銨濃度下，不同碳氮比對轉化率的影響........................ 66
4.3.討論....................................................................................................................69
第五章結論與建議........................................................................................................... 71
5.1. 結論................................................................................................................. 71
5.2. 建議................................................................................................................. 72
第六章參考文獻............................................................................................................... 74
第七章附註目錄................................................................................................................81
附註1………………………………………….….………..…………..……..……81
附註2………………………………………………………..…..….…………..….84
附註3-1…………………………………………..………………..………….…....85
附註3-2……………………………………………….………………………..…..86
附註4…………………………………………………………………..….……....111
附註5-1………………………………………………….…………………..….....117
附註5-2…………………………………………………………………................121








圖目錄
圖1-1.我國生技廠商之產業領域分佈............................................................................ 2
圖1-2.我國生技廠商之地區分佈...……......................................................................... 3
圖1-3.我國生技廠商之實收資本額分佈...…................................................................. 3
圖1-4.我國生技產業研發投資分佈...……..................................................................... 4
圖1-5.我國生技廠商之技術來源...……......................................................................... 4
圖1-6.我國生技廠商之產值分佈...……......................................................................... 5
圖2-1 ubiquinone 的結構圖...................................……………………..........................13
圖2-2 ubiquinone 在哺乳動物細胞中的合成途徑.....................................…............... 16
圖2-3 ubiquinone在原核生物細胞與真核生物細胞合成次序上的差異.......................17
圖3-1 實驗流程圖........................................................................................................... 33
圖3-2 CoQ10 含量與吸收值的檢量線.............................................................................41
圖4-1在兼氣操作下，於28℃，150rpm，植物培養燈照射下培養72小時，其菌體
顏色就會呈紅色(左瓶)和原培養基(右瓶)顏色完全不同………………………48
圖4-2以種瓶培養基為基礎，並在其中加入Mineral salts solution(10ml/L)，對菌體
重量及CoQ10產物轉化率的影響……………………………………..……........49
圖4-3以15g/L yeast extract 為基礎氮源時，不同濃度sucrose對菌體重量及CoQ10產
物轉化率的影響....................................................................................................51
圖4-4以15g/L yeast extract 為基礎氮源時，不同濃度fructose對菌體重量及CoQ10產
物轉化率的影響....................................................................................................52
圖4-5以15g/L yeast extract 為基礎氮源時，不同濃度glucose對菌體重量及CoQ10產
物轉化率的影響....................................................................................................54
圖4-6以2.5g/L glucose 為基礎碳源時，不同濃度yeast extract 對菌體重量及CoQ10
產物轉化率的影響................................................................................................55
圖4-7以2.5g/L glucose 為基礎碳源時，不同濃度peptone 對菌體重量及CoQ10產物
轉化率的影響........................................................................................................57
圖4-8以2.5g/L glucose 為基礎碳源時，不同濃度Ammonium sulfate對菌體重量及
CoQ10產物轉化率的影響.....................................................................................58
圖4-9在2.5 g/L glucose和15g/L yeast extract 的存在下(重量比為1:6)，分別添加不
同濃度硫酸銨對菌體重量及CoQ10產物轉化率的影響……………………….60
圖4-10在2.5 g/L glucose和20g/L peptone的存在下(重量比為1:8)，分別添加不同濃
度硫酸銨對菌體重量及CoQ10產物轉化率的影……………………………….61
圖4-11以2.5 g/L glucose 為基礎碳源，搭配三種不同氮源(如硫酸銨、yeast extract
、peptone)，在照光、pH7-8、150rpm、兼氣、添加金屬離子和溫度28℃的
情況下培養72小時，其菌體重量轉化率及CoQ10產物轉化率………….......63
圖4-12以2.5 g/L glucose 為基礎碳源，搭配單一氮源15g/L yeast extract，在照光、pH7-8、150rpm、兼氣、添加金屬離子和溫度28℃的情況下培養72小時，
其菌體重量轉化率及CoQ10產物轉化率與添加10g/L的硫酸銨對菌體重量
轉化率及CoQ10產物轉化率的影響比較……………………………………...64
圖4-13以2.5 g/L glucose 為基礎碳源，搭配單一氮源20g/L peptone，在照光、
pH7-8、150rpm、兼氣、添加金屬離子和溫度28℃的情況下培養72小時
，其菌體重量轉化率及CoQ10產物轉化率與添加10g/L的硫酸銨對菌體重
量轉化率及CoQ10產物轉化率的影響比較………………………..……….....65
圖4-14 為菌體在生長初期時的情形............................................................................66
圖4-15 為菌體在對數生長期時的情形....................................................................... 66
圖4-16 以2.5 g/L glucose 為基礎碳源，在固定硫酸銨濃度為10g/L下，分別添
加15g/L yeast extract 及20g/L peptone於培養基，在照光、pH7-8、100rpm
、兼氣、添加金屬離子和溫度28℃的情況下其菌體的重量轉化率及CoQ10產
物轉化率的影響………………………………………………………….…...67





表目錄
表1-1 我國生技廠商之產業範圍分類...............................................……………...... 2
表2-1 光合細菌菌體組成............................................................................………......11
表2-2 光合細菌B 族維生素組成……………………………………………………..12
表2-3 CoQ10 在一般應用上的醫療效果.......................................................……........15
表2-4 不同的光合菌其所含的Quinone 成份...............................................................24
表2-5 具有生產ubiquinone 能力的微生物...................................................................25
表2-6 工業發酵上常用的碳源和氮源.......................................................................... 26
表2-7 八種主要培養基和其生化功能以及生長所需的濃度...................................... 26
表2-8 在不同碳源下不同微生物的單位基質菌體轉化率……………….................. 27
表4-1 以種瓶培養基為基礎，並在其中加入Mineral salts solution(10ml/L)，對菌
體重量及CoQ10產物轉化率的影響....................................................................49
表4-2 以15g/L yeast extract 為基礎氮源時，不同濃度sucrose對菌體重量及CoQ10
產物轉化率的影響............................................................................................. 51
表4-3 以15g/L yeast extract 為基礎氮源時，不同濃度fructose對菌體重量及CoQ10
產物轉化率的影響............................................................................................. 53
表4-4 以15g/L yeast extract 為基礎氮源時，不同濃度glucose對菌體重量及CoQ10
產物轉化率的影響............................................................................................. 54
表4-5 以2.5g/L glucose 為基礎碳源時，不同濃度yeast extract 對菌體重量及CoQ10
產物轉化率的影響............................................................................................. 56
表4-6 以2.5g/L glucose 為基礎碳源時，不同濃度peptone 對菌體重量及CoQ10產
物轉化率的影響................................................................................................. 57
表4-7 以2.5g/L glucose 為基礎碳源時，不同濃度Ammonium sulfate對菌體重量
及CoQ10產物轉化率的影響……………………………………………….…..59
表4-8 在2.5 g/L glucose和15g/L yeast extract 的存在下(重量比為1:6)，分別添加
不同濃度硫酸銨對菌體重量及CoQ10產物轉化率的影響…………………...60
表4-9 在2.5 g/L glucose和20g/L peptone的存在下(重量比為1:8)，分別添加不同
濃度硫酸銨對菌體重量及CoQ10產物轉化率的影響…………………………61
表4-10以2.5 g/L glucose 為基礎碳源，在固定硫酸銨濃度為10g/L下，以Yeast extract
為氮源(重量比:1:6)，在照光、pH7-8、100rpm、兼氣、添加金屬離子和溫度
28℃的情況下其菌體的重量轉化率及CoQ10產物轉化率隨培養時間長短之變
化………………………………………………………………………………..68
表4-11以2.5 g/L glucose 為基礎碳源，在固定硫酸銨濃度為10g/L下，以Peptone
為氮源(重量比:1:8)，在照光、pH7-8、100rpm、兼氣、添加金屬離子和溫
度28℃的情況下其菌體的重量轉化率及CoQ10產物轉化率隨培養時間長短
之變化…………………………………………………………………..………68
表4-12固定濃度CoQ10在不同pH值時，以丙酮及氯仿萃取之回收率比較…………70

小林正泰。1981。養魚與光合細菌。養殖 8: 56-59.
黃鈞卜、陳琴、韋勇剛、唐時秀。2004。光合細菌在水產養殖上的應用概況。廣西大學動物科技學院 530005.
胡淼琳。1994。Coenzyme Q10 的生化營養性質以及它的醫療功效。自由基生物學與醫學 2(1): 46-53.
郭秋媚、劉恆仲。2004。輔酶Q10之簡介。食品工業 36(12): 42-56.
劉昌峰。2001。探討不同培養基組成對光合菌Rhodobacter sphaeroides生產Coenzyme Q10之研究。中央大學化工所碩士論文 pp.7-33.
Abee T, Wal FJ, Hellingwerf KJ and Konings WN. 1989. Binding-protein-dependent Alanine transport in Rhodobacter sphaeroides is regulated by the internal pH. Journal of bacteriology 171:5148-5154.
Alleva R, Scararmucci A and Mantero F. 1997. The protective role of ubiquinol-10 against formation of lipid hydroperoxides in human seminal fluid. Molec. Aspects Med. 18: 221-228.
Asahi Chemical Industry Co. Ltd. 1984. Preparation of Coenzyme Q10. Jpn. Kokai Tokkyo Koho JP, 84/59, 197
Baggio E, Gandini R,Plancher AC, Passeri M and Carmosino G. 1994. Italian Multicenter Study on the Safety and Efficacy of Coenzyme Q10 as Adjunctive Therapy in Heart Failure . Molec Aspects Med. 15:s287-s294.
Boa JM and LeDuy A. 1987. Pullulan from peat hydrolyzate fermentation kinetics. Biotechnol. Bioeng. 30:463-470.
Burgess JG, Miyashita H, Sudo H and Matsunaga T. 1991. Antibiotic production by the marine photosynthetic bacterium Chromatium purpuratum NKPB 031704: localization of activity to the chromatophores. FEMS Microbio. Lett. 84: 301-305.
Carr NG and Exell G. 1965. Ubiquinone concentrations in Athiorhodaceae growth under various environmental conditions. Journal of Biochem. 96: 688-692.
Cordts ML and Gibson J. 1987. Ammonium and methylammonium transport in Rhodobacter sphaeroides. Journal of bacteriology 169:1632-1638.
Crane FL, Hatefi Y, Lester RI and Widmer C. 1957. Isolation of a quinone from beef heart mitochondria. Biochimica et Biophys. Acta. 25: 220-221.
Dallner G and Sindelar PJ. 2000. Regulation of ubiquinone metabolism. Free Radical Biology and Medicine 285-294.
Darrouzet E and Daldal F. 2003. Protein-protein interaction between cytochrome b and the Fe-S protein subunits during QH2 oxidation and large-scale domain movement in the bc1 complex. Biochemistry 42:1499-507.
Detcho AS, Anatoly NO, Peter JQ and Valerian EK. 1995 .Ubiquinone-dependent recycling of vitamin E radicals by superoxide. Archieves of Biochemistry and Biophysics. 323(2) : 343–351.
Do TQ, Hsu AY, Jonassen T, Lee PT and Clarke CF. 2001. A defect in coenzyme Q biosynthesis is responsible for the respiratory deficiency in Saccharomyces cerevisiae abc1 mutants. J. Biol. Chem. 276: 18161-18168.
Emile GB. 1999. Cardiovascular diseases, oxidative stress and antioxidants: the decisive role. Cardiovascular Research. 43: 248–249.
Elibol M and Mavituna F. 1999. A kinetic model for actinorhodin production by
Streptomyces coelicolor A3. Process Biochemistry. 34:625-631.
Ernster L and Dallner G. 1995. Biochemical, physiological and medical aspects
of ubiquinone function. Biochinica et Biophysica Acta. 1271:195-204.
Frederick LC and Placido N. 1997. The diversity of coenzyme Q function, Molec.Aspects Med. 18: s1-s6.
Folkers K, Langsjoen PH, Willis R, Richardson P, Xia L, Ye C and Tamagawa H. 1990. Lovastatin decrease coenzyme Q levels in humans.Proc. Natl. Acad. Sci. 87: 8931-8934.
Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, Greco AV and Littarru GP. 1993. Evidence of plasma CoQ10 lowering effect by HMG-CoA reductase inhibitors. J. Clin. Pharmocol. 33: 226-229.
Glenn J, Whitman r and Koki N. 1997. The mechanisms of coenzyme Q10 as therapy for myocardial ischemia reperfusion injury. Molec.Aspects Med. 18: s195-s203.
Hans N, Andrey VK, Katrin S and Lars G. 2001. The Multiple Functions of Coenzyme Q. Bioorganic Chemistry. 29: 1–13.
Herbert RA. 1976. Isolation and identification of photosynthetic bacteria (Rhodospirillaceae) from Antarctic marine and freshwater sediments. J. Appl. Bacteriol. 41: 75-80.
Hiraishi A. 1989. Quinone Profiling of Bacterial Communities in Natural and Synthetic Sewage Activated Sludge for Enhanced Phosphate Removal . Appl Environ Microbiol. 64: 992-998.
Hirotani H, Ohigash, H, Kobayashi M, Koshimizu K and Takahashi E.
1991. Inactivation of T5 phage by cis-vaccenic acid, an antivirus substance from Rhodopseudomonas capsulata, and by unsaturated fatty acids and related alcohols. FEMS Microbiol. Lett. 77:13.
Hochman A and Shemesh A. 1987. Purification and characterization of a catalase-peroxidase from the photosynthetic bacterium Rhodopseudomonas capsulate. Biol. Chem. 262: 6871-6876.
Hughes K, Lee BL, Feng X, Lee J and Ong CN. 2002. Coenzyme Q10 and differences in coronary heart disease risk in asian indians and chinese . Free Radical Biology＆Medicine. 32-2:132-138.
Imhoff JF, Truper HG and Pfennig N. 1984. Rearrangement of the species and genus of the phototrophic "Purple nonsulfur bacteria. Int. J. Syst. Bacteriol. 34:340.
Ishimura M, Honda S, Uedaira H, Odahara T and Miyake J. 1995. Thermal denaturation of photosynthetic membrane proteins from Rhodobacter sphaeroides. Thermochimica Acta 266:355-364.
Japan Synthetic Rubber Co. Ltd. 1982. Process for the production of coenzyme Q. Jpn , Kokai Tokkyo Koho JP,82/43, 691.
Kaplan P, Kucera I and Dadak V. 1993.Effect of oxygen on ubiquinone-10
production by Paracoccus denitrificans. Biotech. Lett. 15:1001-1002.
Kessi J. 2006. Enzymic systems proposed to be involved in the dissimilatory reduction of selenite in the purple non-sulfur bacteria rhodospirillum rubrum and Rhodobacter capsulatus. Microbiology152:731-43.
Kho DH, Yoo SB, Kim JS, Kim EJ and Lee JK. 2004. Characterization of Cu- and Zn-containing superoxide dismutase of Rhodobacter sphaeroides. FEMS Microbiology Letters 234:261-267.
Ko,Uchida,Kinya,Izumi and Hideichi. 1979. Process for the production coenzyme Q.sub.10. Aida;ko,Japan. U.S. Patent 4,220,719.
Kuratsu Y and Hagino H. 1984a. Effect of Ammonium Ion on coenzyme Q10 Fermentation by Agrobacterium species. Agric. Biol. Chem. 48: 1347-1348.
Kuratsu Y, Sakurai M and Hagino H. 1984b. Aeration-agitation effect on
coenzyme Q10 production by Agrobacterium species. J. Ferment.Technol. 62:305-308.
Langsjoen PH, Langsjoen A, Willis R and Folkers K. 1997. Treatment of
Hypertrophic Cardiomyopathy with Coenzyme Q10. Molec. Aspects.Med.
18:s145-s151.
Langsjoen PH, Langsjoen A, Willis R and Folkers K. 1994. Usefulness of Coenzyme Q10 in Clinical Cardiology: A Long-term Study . Molec Aspects Med. 15:s165-s175.
Langsjoen PH, Langsjoen A, Willis R and Folkers K. 1994. Treatment of Essential Hypertension with Coenzyme Q10. Molec Aspects Med. 15:s265-s272.
Li Y, Chen J, Liang D-F and Lun S-Y. 2000. Effect of nitrogen sources and
nitrogen concentration on the production of pyruate by Torulopsis glabrata. J. Biotech. 81: 27-34.
Littarru GP, Lippa S, Oradei A, Fiorni RM and Mazzanti L. 1991. Metaolic and
diagnostic implications of blood CoQ10 level. Biomedical and clinical aspects of coenzyme Q 6:1-555.
Luedeking R and Piret EL. 1959. A kinetic study of the lactic acid fermentation:
Batch process at controlled Ph. J. Biochem. Microbiol. Technol.Eng. 1: 363-394.
Maria LU and Priscilla MC. 2003. Oxidative stress, exercise, and antioxidant supplementation. Toxicology 189: 41-54.
Matsumura M, Kobayashi T and Aiba S. 1983. Anaerobic production of ubiquinone-10
by Paracoccus denitrificans. Eur. J. Microbiol.Biotechnol. 17: 85-89.
Mattila P and Kumpulainen J. 2001. coenzymes Q9 and Q10:Contents in Foods and Dietary Intake. Journal of Food Composition and Analysis. 14:409-417.
Miki K, Sogabe S, Uno A, Ezoe T, Kasai N, Saeda M, Matsuura Y and Miki M. 1994. Application of an automatic molecular-replacement procedure to crystal structure analysis of cytochrome c2 from Rhodopseudomonas viridis. Acta Cryst.
D50:271-275.
Morton RA, Festenstein GN, Heaton FW and Lowe JS. 1955. A constituent of the unsaponifiable portion of animal tissue lipids (λmax. mμ.). J. Biochem. 59: 558-566.
Natori Y and Nagasaki T. 1981. Enhancement of Coenzyme Q10 Accumulation by Mutation and Effects of Medium Components on the Formation of
Coenzyme Q Homologs by Pseudomonas N842 and Mutants. Agric.Biol. Chem. 45: 2175-2182.
Nishikawa S, Watanabe K, Tanaka T, Miyachi N, Hotta Y and Murooka Y. 1999. Rhodobacter sphaeroides mutants which accumulate 5-Aminolevulinic acid under aerobic and dark conditions. Journal of Bioscience and Bioengineering. 87:798-804.
Nohi H, Gille L and Staniek K. 1997. Emdeogenous and exogenous of redox-properties of coenzyme Q. Molec.Aspects Med. 18:s33-s40.
Oelze J, Pahlke W and Bohm S. 1975. Ubiquinone 10 formation in Rhodospirillum rubrum under different culture conditions. Arch. Microbiol. 102: 65-69.
Overvad K, Diamant B , Holm L , Holmer G and Mortensen SA. 1999. Coenzyme Q10 in health and disease. European Journal of Clinical Nutrition. 53:764-770.
Page AC, Gale P, Wallick H, Walton RB, Mcdaniel LE, Woodruff HB and Folkers K. 1960. Coenzymes Q. XⅦ. Isolation of Coenzyme Q10 from Bacterial Fermentation. Archi. Biochem.BiopHysic. 89: 318-321.
Padilla S, Jonassen T, Jimenez-Hidalgo MJ, Fernandez-Ayala DJM., Lopez-Lluch GM, Marbois B, Navas P, Clarke CF and Santos-Ocana C. 2004. Demethoxy-Q, an intermediate of coenzyme Q biosynthesis, fails to support respiration in Saccharomyces cervisiase and lacks antioxidant activity. J. Biol. Chem. 279:25995-26004.
Pinches A and Pallent LJ. 1986. Rate and yield relationship in the production of
xanthan gum by batch fermentations using complex and chemically defined growth media. Biotechnol. Bioeng. 28: 1484-1496.
Robinson DK and Wang DIC. 1988. A transport controlled bioreactor for the simultaneous production and concentration of xanthan gum. Biotechnol. Prog. 4:231-241.
Ruth AH, Richard AW and Ann EH. 2003. Ubiquinone binding protein used for determination of coenzyme Q. Analytical Biochemistry 320:125-128.
Sakato K, Tanaka H, Shibata S and Kuratsu Y. 1992. Agitation-aeration studies on coenzyme Q10 production using Rhodopseudomonas sphaeroides.Biotechnol. Appl.Biochem. 16: 19-28.
Sasaki K and Nagai S. 1979. The optimum pH and temperature for the aerobic growth of Rhodopseudomonas gelatinosa, and vitamin B12 and ubiquinone formation on a starch mediumRhodopseudomonas gelatinosa. J. Ferment. Technol. 57:383-386.
Sasaki K, Tanaka T, Nishizawa Y and Hayashi M. 1990. Production of herbicide, 5-aminolevulinic acid, by Rhodobacter sphaeroides using the effluent of swine waste from an anaerobic digestor. Appl. Microbiol.Biotechnol. 32:727-731.
Sasikala C and Ramana CV. 1995. Biotechnological potentials of anoxygenic phototrophic bacteria .2. Biopolyesters, biopesticide, biofuel, and biofertilizer Adv. Appl. Microbiol. 41: 227-278.
Sasikala K, Ramana C and Rao PA. 1993. Anoxygenic Phototrophic bacteria:Physiology and advances in hydrogen production technology. Adv. Appl. Microbiol. 38: 211.
Seki H, Suzuki A and Mitsueda SI. 1998. Biosorption of heavy metal ions on Rhodobacter sphaeroides and Alcaligenes eutrophus H16. Journal of colloid and interface science. 197:185-190.
Serdyuk OP, Smolygina LD, Kobzar EF and Gogotov IN. 1993. Occurrence of plant hormones in cells of the phototrophic purple bacterium Rhodospirillum rubrum 1R. FEMS Microbiol. Lett. 109:113.
Shepherd JA, Poon WW, Myles DC and Clarke CF. 1996. The biosynthesis of ubiquinone: Synthesis and enzymatic modification of biosynthetic precursors. Tetrahedron Letters. 37:2395-2398.
Shuler ML and Kargi F. 1979.. A generalized differential specific rate equation for microbial growth. Biotechnol. Bioeng. 21:1871-1875.
Shuler ML and Kargi F. 1992. Bioprocesses engineering basic concept.159-161
Sinatra ST. 1997. Refractory Congestive Heart Failure Successfully Managed
with High Dose Coeznyme Q10 Administration. Molec. Aspects. Med. 18: s299-s305.
Tanaka T, Nishigaki T, Yamada T, Watanabe T and Husimi Y. 1988. Bacterial bioassay of microgram to subnanogram quantites of glucose. Biotechnol. Appl. Biochem. 10:428-434.
Tang PH, Miles MV, Miles L, Quinlan J, Wong B, Wenisch A and Bove K. 2004. Measurement of reduced and oxidized coenzyme Q9 and coenzyme Q10 levels in mouse tissues by HPLC with coulometric detection. Clinica Chimica Acta. 341:173-184.
Urakami T and Yoshida T. 1993. Production of ubiquinone and bacteriochlorophyll a by Rhodobacter sphaeroides and Rhodobacter sulfidophilus. J. Ferment. Bioeng. 76: 191-194.
Vrati S. 1984. Single cell protein production by photosythetic bacteria grown on the clarified effluents of biogas plant. Appl. Microbiol. Biotechnol. 19: 199.
Wang H and Noren A. 2006. Metabolic regulation of nitrogen fixation in Rhodospirillum rubrum. Biochem soc Trans.34:160-161.
Wang ZY, Shimonaga M, Suzuki H, Kobayashi M and Nozawa T. 2003. Purification and characterification of the polypeptides of core light-harvesting complexes from purple sulfur bacteria. Photosynth Res. 78:133-141.
William HS and Jeffery WL. 2004. Evaluation of ubiquinone concentration and mitochondrial function relative to cerivastatin-induced skeletal myopathy in rats. Toxicology and Applied Pharmacology. 194: 10-23.
Yalcin A, Kilinc E, Sagcan A and Kultursay H. 2004. Coenzyme Q10 concentrations in coronary artery disease . Clinical Biochemistry .37:706-709.
Yasuyuki Kaneko and Anjyo. 1981. Method for Producing coenzyme Q10. Nagoya University,Nagoya,Japan. U.S. Patent 4,367,288.
Zhang X-W, Sun T, Sun Z-Y, Liu X and Gu D-X. 1998. Time-dependent kinetic models for glutamic acid fermentation. Enzyme and Microbiol Technology. 22: 205-209.