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Coenzyme Q10 production in a 150-l reactor by a mutant strain of Rhodobacter sphaeroides

  • Original Paper
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Journal of Industrial Microbiology & Biotechnology

Abstract

For the commercial production of CoQ10, batch-type fermentations were attempted in a 150-l fermenter using a mutant strain of R. sphaeroides. Optimum temperature and initial aeration rate were found to be 30°C and 2 vvm, respectively. Under optimum fermentation conditions, the maximum value of specific CoQ10 content was achieved reproducibly as 6.34 mg/g DCW after 24 h, with 3.02 g/l of DCW. During the fermentation, aeration shift (from the adequate aeration at the early growth phase to the limited aeration in active cellular metabolism) was a key factor in CoQ10 production for scale-up. A higher value of the specific CoQ10 content (8.12 mg/g DCW) was achieved in fed-batch fermentation and comparable to those produced by the pilot-scale fed-batch fermentations of A. tumefaciens, which indicated that the mutant strain of R. sphaeroides used in this study was a potential high CoQ10 producer. This is the first detailed study to demonstrate a pilot-scale production of CoQ10 using a mutant strain of R. sphaeroides.

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References

  1. Ernster L, Dallner G (1995) Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271:195–204

    PubMed  Google Scholar 

  2. Grant CM, Maclver FH, Dawes IW (1997) Mitochondrial function is required for resistance to oxidative stress in the yeast Saccharomyces cerevisiae. FEBS Lett 410:219–222

    Article  CAS  PubMed  Google Scholar 

  3. Wu ZF, Weng PF, Du GC, Chen J (2001) Advances of coenzyme Q10 function studies. J Ningbo Univ 2:85–88

    Google Scholar 

  4. James AM, Smith RAJ, Murphy MP (2004) Antioxidant and prooxidant properties of mitochondrial coenzyme Q. Arch Biochem Biophys 423:47–56. doi:10.1016/j.abb.2003.12.025

    Article  CAS  PubMed  Google Scholar 

  5. Gale PH, Koniuszy FR, Page AG Jr, Folkers K (1961) Coenzyme Q. XXIV. On the significance of coenzyme Q10 in human tissues. Arch Biochem Biophys 93:211–213

    Article  CAS  PubMed  Google Scholar 

  6. Sasaki K, Watanabe M, Suda Y, Ishizuka A, Noparatnaraporn N (2005) Applications of photosynthetic bacteria for medical fields. J Biosci Bioeng 100:481–488. doi:10.1263/jbb.100.481

    Article  CAS  PubMed  Google Scholar 

  7. Takahashi S, Nishino T, Koyama T (2003) Isolation and expression of Paracoccus dentrificans decaprenyl diphosphate synthese gene for production of ubiquinone-10 in Escherichia coli. Biochem Eng J 16:183–190. doi:10.1016/S1369-703X(03)00035-4

    Article  CAS  Google Scholar 

  8. Zhang D, Shrestha B, Niu W, Tian P, Tan T (2007) Phenotypes and fed-batch fermentation of ubiquinone-overproducing fission yeast using ppt1 gene. J Biotechnol 128:120–131. doi:10.1016/j.jbiotec.2006.09.012

    Article  CAS  PubMed  Google Scholar 

  9. Negishi E, Liou SY, Xu C, Huo S (2002) A novel, highly selective, and general methodology for the synthesis of 1, 5-diene-containing oligoisoprenoids of all possible geometrical combinations exemplified by an iterative and convergent synthesis of coenzyme Q10. Org Lett 4:261–264. doi:10.1021/ol010263d

    Article  CAS  PubMed  Google Scholar 

  10. Lipshutz BH, Mollard P, Pfeiffer SS, Chrisman W (2002) A short, highly efficient synthesis of coenzyme Q10. J Am Chem Soc 124:14282–14283. doi:10.1021/ja021015v

    Article  CAS  PubMed  Google Scholar 

  11. Ha SJ, Kim SY, Seo JH, Oh DK, Lee JK (2007) Optimization of culture conditions and scale-up to pilot and plant scales for coenzyme Q10 production by Agrobacterium tumefaciens. Appl Microbiol Biotechnol 74:974–980. doi:10.1007/s00253-006-0744-4

    Article  CAS  PubMed  Google Scholar 

  12. Choi JH, Seo YW, Seo JH (2005) Biotechnological production and applications of coenzyme Q10. Appl Microbiol Biotechnol 68:9–15. doi:10.1007/s00253-005-1946-x

    Article  CAS  PubMed  Google Scholar 

  13. Lee JK, Her G, Kim SY, Seo JH (2004) Cloning and functional expression of the dps gene encoding decaprenyl diphosphate synthase from Agrobacterium tumefaciens. Biotechnol Prog 20:51–56

    Article  CAS  PubMed  Google Scholar 

  14. Park YC, Kim SJ, Choi JH, Lee WH, Park KM, Kawamukai M, Ryu YW, Seo JH (2005) Batch and fed-batch production of coenzyme Q10 in recombinant Escherichia coli containing the decaprenyl diphosphate synthase gene from Gluconobacter suboxydans. Appl Microbiol Biotechnol 67:192–196. doi:10.1007/s00253-004-1743-y

    Article  CAS  PubMed  Google Scholar 

  15. Matthews PD, Wurtzel ET (2000) Metabolic engineering of carotenoid precursor pool with expression of deoxyxylulose phosphate synthase. Appl Microbiol Biotechnol 53:396–400

    Article  CAS  PubMed  Google Scholar 

  16. Zahiria HS, Yoon SH, Keasling JD, Lee SH, Kim SW, Yoon SC, Shin YC (2006) Coenzyme Q10 production in recombinant Escherichia coli strains engineered with a heterologous decaprenyl diphosphate synthase gene and foreign mevalonate pathway. Metab Eng 8:406–416. doi:10.1016/j-ymben.2006.05.002

    Article  Google Scholar 

  17. Clauis CP, Burja AM, Martin VJJ (2007) Current prospects for the production of coenzyme Q10 in microbes. Trends Biotechnol 25:514–521. doi:10.1016/j.tibtech.2007.08.008

    Article  Google Scholar 

  18. Zhong W, Fang J, Liu H, Wang X (2009) Enhanced production of CoQ10 by newly isolated Sphingomonas sp. ZUTE03 with a coupled fermentation-extraction process. J Ind Microbiol Biotechnol 36:687–693. doi:10.1007/s10295-009-0538-7

    Article  CAS  PubMed  Google Scholar 

  19. Sakato K, Tanaka H, Shibata S, Kuratsu Y (1992) Agitation-aeration studies on coenzyme Q10 production using Rhodopseudomonas spheroids. Biotechnol Appl Biochem 16:19–28

    CAS  Google Scholar 

  20. Jeong S-K, Dao VT, Kien N, Kim JK (2008) Effects of pH and light irradiation on coenzyme Q10 production using Rhodobacter sphaeroides. J Fish Sci Technol 11:219–223

    CAS  Google Scholar 

  21. Hoekema S, Douma RD, Janssen M, Tramper J, Wijffels RH (2006) Controlling light-use by Rhodobacter capsulatus continuous cultures in a flat-panel photobioreactor. Biotechnol Bioeng 95:613–626

    Article  CAS  PubMed  Google Scholar 

  22. Takeno K, Sasaki K, Nishio N (1999) Removal of phosphorus from oyster farm mud sediment using a photosynthetic bacterium, Rhodobacter sphaeroides IL106. J Biosci Bioeng 88:410–415

    Article  CAS  PubMed  Google Scholar 

  23. Nagadomi H, Kitamura T, Watanabe M, Sasaki K (2000) Simultaneous removal of chemical oxygen demand (COD), phosphate, nitrate and hydrogen sulphide in the synthetic sewage wastewater using porous ceramic immobilized photosynthetic bacteria. Biotechnol Lett 22:1369–1374

    Article  CAS  Google Scholar 

  24. Jeong S-K, Cho J-S, Kong I-S, Jeong HD, Kim JK (2009) Purification of aquarium water by PVA gel-immobilized photosynthetic bacteria during goldfish rearing. Biotechnol Bioproces Eng 14:238–247. doi:10.1007/s12257-008-0195-0

    Article  CAS  Google Scholar 

  25. Basak N, Das D (2009) Photofermentative hydrogen production using purple non-sulfur bacteria Rhodobacter sphaeroides O.U.001 in an annular photobioreactor: a case study. Biomass Bioenergy 33:911–1012. doi:10.1016/j.biombioe.2009.02.007

    Article  CAS  Google Scholar 

  26. Uyar B, Eroglu I, Yucel M, Gunduz U (2009) Photofermentative hydrogen production from volatile fatty acids in dark fermentation effluents. Int J Hydrogen Energy 34:4517–4523. doi:10.1016/j.ijhydene.2008.07.057

    Article  CAS  Google Scholar 

  27. Vatsala TM, Raj SM, Manimaran A (2008) A pilot-scale study of biohydrogen production from distillery effluent using defined bacterial co-culture. Int J Hydrogen Energy 33:5404–5415. doi:10.1016/j.ijhydene.2008.07.015

    Article  CAS  Google Scholar 

  28. Rambir KD, Bhansali AG, Behera BK (2008) Process conditions optimization for CoQ10 production by Paracoccus species. J Biotechnol 136:S513. doi:10.1016/j.jbiotec.2008.07.642

    Article  Google Scholar 

  29. Jeong S-K, Ahn SC, Kong IS, Kim JK (2008) Isolation and identification of a photosynthetic bacterium containing high content of coenzyme Q10. J Fish Sci Technol 11:172–176

    CAS  Google Scholar 

  30. Yoshida H, Kotani Y, Ochiai K, Araki K (1998) Production of ubiquinone-10 using bacteria. J Gen Appl Microbiol 44:19–26

    Article  CAS  PubMed  Google Scholar 

  31. Jeong S-K, Kim JK (2008) Effect of aeration-agitation on coenzyme Q10 production using Rhodobacter sphaeroides. J Fish Sci Technol 11:224–228

    CAS  Google Scholar 

  32. Gu S-B, Yao J-M, Yuan Q-P, Xue P-J, Zheng Z-M, Yu Z-L (2006) Kinetics of Agrobacterium tumefaciens ubiquinone-10 batch production. Process Biochem 41:1908–1912. doi:10.1016/j.procbio.2006.04.002

    Article  CAS  Google Scholar 

  33. Matsumura M, Kobayashi T, Aiba S (1983) Anaerobic production of ubiquinone-10 by Paracoccus dentrificans. Eur J Appl Microbiol Biotechnol 17:85–89

    Article  CAS  Google Scholar 

  34. Neter J, Wasserman W, Kutner MH (1985) Applied linear statistical models, 2nd edn. IRWIN, Homewood, pp 574–579

    Google Scholar 

  35. Ssaki K, Nagai S (1979) The optimum pH and temperature for the aerobic growth of Rhodopseudomonas gelatinosa, and vitamin B12 and ubiquinone formation on a starch medium. J Ferment Technol 57:383–386

    Google Scholar 

  36. Kokua H, Eroglu I, Gunduz U, Yucel M, Turker L (2003) Aspects of the metabolism of hydrogen production by Rhodobacter sphaeroides. Int J Hydrogen Energy 27:1315–1329

    Article  Google Scholar 

  37. Yen HW, Shih TY (2009) Coenzyme Q10 production by Rhodobacter sphaeroides in stirred tank and in airlift bioreactor. Bioprocess Biosyst Eng 32:711–716. doi:10.1007/s00449-008-0294-5

    Article  CAS  PubMed  Google Scholar 

  38. Nielsen J, Villadsen J (1994) Bioreaction engineering principles. Plenum Press, New York

    Google Scholar 

  39. Saunders VA, Jones OTG (1974) Properties of the cytochrome a-like material developed in the photosynthetic bacterium Rhodopseudomonas spheroides when grown aerobically. BBA Bioenerg 333:439–445

    Article  CAS  Google Scholar 

  40. Yamada Y, Haneda K, Murayama S, Shiomi S (1991) Application of fuzzy control system fermentation. J Chem Eng 24:94–99

    Article  CAS  Google Scholar 

  41. Yen HW, Chiu CH (2007) The influences of aerobic-dark and anaerobic-light cultivation on CoQ10 production by Rhodobacter sphaeroides in the submerged fermenter. Enzyme Microb Technol 41:600–604. doi:10.1016/j.enzmictec.2007.05.005

    Article  CAS  Google Scholar 

  42. Bylund F, Collet E, Enfors S-O, Larsson G (1998) Substrate gradient formation in the large-scale bioreactor lower cell yield and increases by-product formation. Bioproc Eng 18:171–180

    Article  CAS  Google Scholar 

  43. Xu B, Jahic M, Blomsten G, Enfors S-O (1999) Glucose overflow metabolism and mixed acid fermentation in aerobic large-scale fed-batch processes with Escherichia coli. Appl Microbiol Biotechnol 51:564–571

    Article  PubMed  Google Scholar 

  44. Humphrey A (1998) Shake flask to fermentor: what have we learned? Biotechnol Prog 14:3–7

    Article  CAS  Google Scholar 

  45. Kuratu Y, Sakurai M, Hagino H, Inuzuka K (1984) Aeration-agitation effect on coenzyme Q10 production by Agrobacterium species. J Ferment Technol 62:305–308

    Google Scholar 

  46. Wu Z, Du G, Chen J (2003) Effects of dissolved oxygen concentration and DO-stat feeding strategy on CoQ10 production with Rhizobium radiobacter. World J Microbiol Biotechnol 19:925–928

    Article  CAS  Google Scholar 

  47. Urakami T, Yoshida T (1993) Production of ubiquinone and bacteriochlorophyll α by Rhodobacter sphaeroides and Rhodobacter sulfidophilus. J Ferment Bioeng 76:191–194

    Article  CAS  Google Scholar 

  48. Ha SJ, Kim SY, Seo JH, Moon HJ, Lee KM, Lee JK (2007) Controlling the sucrose concentration increases Coenzyme Q10 production in fed-batch culture of Agrobacterium tumefaciens. Appl Microbiol Biotechnol 76:109–116. doi:10.1007/s00253-007-0995-8

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This research was supported by a grant (M2007-05) from the Marine Bioprocess Research Center of the Marine Bio 21 Center funded by the Ministry of Land, Transport and Maritime, Republic of Korea.

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Authors and Affiliations

  1. Division of Food Science and Biotechnology, Pukyong National University, Busan, 608-737, Korea

    Nguyen Ba Kien, In-Soo Kong & Joong Kyun Kim

  2. Division of Applied Chemical Engineering, Pukyong National University, Busan, 608-739, Korea

    Min-Gyu Lee

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  1. Nguyen Ba Kien
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  2. In-Soo Kong
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Correspondence to Joong Kyun Kim.

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Kien, N.B., Kong, IS., Lee, MG. et al. Coenzyme Q10 production in a 150-l reactor by a mutant strain of Rhodobacter sphaeroides . J Ind Microbiol Biotechnol 37, 521–529 (2010). https://doi.org/10.1007/s10295-010-0699-4

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  • DOI: https://doi.org/10.1007/s10295-010-0699-4

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