US009926580B2  (12)  United States Patent  Yajima et al.  (IO)  Patent No.:  US 9,926,580 B2  (45)  Date of Patent:  *Mar.27,2018  (54)  PROCESS FOR PRODUCING COENZYME  QlO  (71)  Applicant:  KANEKA CORPORATION,  Osaka-shi (JP)  (72)  Inventors:  Kazuyoshi Yajima,  Hyogo (JP);  Takahisa Kato,  Hyogo (JP);  Akihisa  Kanda,  Osaka (JP);  Shiro Kitamura,  Hyogo (JP);  Yasuyoshi Ueda,  Hyogo  (JP)  (73)  Assignee:  KANEKA CORPORATION,  Osaka  (JP)  ( *)  Notice:  Subject to any disclaimer, the term ofthis  patent is extended or adjusted under 35  U.S.C. 154(b) by O days.  This patent is subject to a terminal dis- claimer.  (21)  Appl. No.:  15/076,025  (22)  Filed:  Mar. 21, 2016  (62)  Division of application No. 13/020,500, filed on Feb.  3, 2011, now Pat. No. 9,315,839, which is a division  of application No. 11/981,181, filed on Oct. 31, 2007,  now Pat. No. 7,910,340, which is a division of  application No. 10/500,249, filed as application No.  PCT/JP02/13766 on Dec. 27, 2002, now abandoned.  (51)  Int. Cl.  (52)  U.S. Cl.  CPC ..  C12P  7166  (2013.01);  C12P  7122  (2013.01)  ( 58)  Field of Classification Search  CPC ......................................................... C12P 7/66  (65)  Prior Publication Data  Related U.S. Application Data  (30)  Foreign Application Priority Data  (56)  References Cited  U.S. PATENT DOCUMENTS  (57)  ABSTRACT  17 Claims, 1 Drawing Sheet  OTHER PUBLICATIONS  FOREIGN PATENT DOCUMENTS  US 2016/0304915 Al  Oct. 20, 2016  Dec. 27, 2001  (JP) ................................. 2001-398545  See application file for complete search history.  A process for producing on an industrial scale the oxidized  coenzyme Q$_{10}$ , includes culturing a reduced coenzyme Q 10 - producing microorganism selected from the group consist› ing of the genus  Rhodobacter,  the genus  Saitoella,  the genus  Schizosaccharomyces  and the genus  Trichosporon,  to obtain  microbial cells containing reduced coenzyme Q$_{10 }$at a ratio  of not less than 70 mole% among the entire coenzymes Q$_{10}$;  and one of: (a) oxidizing thus-obtained reduced coenzyme  Q$_{10 }$ to oxidized coenzyme Q$_{10 }$ and then extracting the  oxidized coenzyme Q$_{10 }$by an organic solvent; or (b) extract› ing reduced coenzyme Q$_{10 }$by an organic solvent and oxi› dizing the extracted reduced coenzyme Q$_{10 }$ to oxidized  coenzyme Q$_{10 }$.  Wakabayashi et al. Biol Pharm Bull, 1994, 17(8): 998-1002.*  Yoshida et al. J Gen Appl Microbiol., 1998, 44, 19-28.*  Takada, Masahiro et al "Studies on Reduced and Oxidized Coen› zyme Q (Ubiquinones): The Determination Oxidation-Reduction  LEvels of Coenzyme Q in Mitochondria, Microsomes and Plasma  by High-Performance Liquid Chromatography," Biochimica et  Biophysica Acta, 1982, vol. 679, pp. 308-314.  Yoshida, Hajime et al "Production ofubiquinone-10 using bacteria,"  J. Gen. Microbiol. 1998, vol. 44, pp. 19-26.  Disch, Andrea et al., "On the Absence of the Glyceraldehyde  3-Phosphate/Pyruvate Pathway for Isoprenoid Biosynthesis in  Fungi and Yeasts," FEMS Microbiology Letters, vol. 168, No. 2,  1998, pp. 201-208.  Kockova-Kratochvilova, A. et al., "Die Beziehungen innerhalb der  Gattung Cryptococcus (Sanfelice) Vuillemin", Zbl. Bakt. Abt. 11,  Bd., vol. 131, No. 7, 1976, pp. 610-631.  Natori,  Y.  et al., "Production of Coenzyme Qlo by Pseudomonas  N842", Agric. Biol. Chem., vol, 42, No. 9, 1978, pp. 1799-1800.  (Continued)  (Continued)  Primary Examiner  - Vera Afremova  (74)  Attorney, Agent, or Firm  - Westerman, Hattori,  Daniels  & Adrian, LLP  3,066,080 A  11/1962 Folkers  3,769,170 A  *  10/1973 Kondo ...................... Cl2P 7/66  435/133  4,220,719 A  9/1980 Aida et al.  6,156,802 A  *  12/2000 Mae.  A61K 31/122  514/690  7,910,340 B2 *  3/2011 Yajima ...................... Cl2P 7/66  435/133  9,315,839 B2 *  4/2016 Yajima ...................... Cl2P 7/22  C12P  7166  C12P  7122  (2006.01)  (2006.01)  DE  236552 Al  11/1986  EP  0051921 Al  5/1982  EP  0073134 A2  3/1983  EP  0956854 Al  11/1999  EP  1 123 979  *  8/2001  EP  1123979 Al  8/2001  EP  1336657 Al  8/2003  EP  1354957 Al  10/2003  EP  1386905 Al  2/2004  EP  1391515 Al  2/2004  EP  1408024 Al  4/2004  EP  1415969 Al  5/2004  EP  1415970 Al  5/2004  EP  1415971 Al  5/2004  EP  1415972 Al  5/2004  EP  1415973 Al  5/2004  EP  1440962 Al  7/2004  EP  1452174 Al  9/2004  GB  930752  A  7 /1963  JP  48-8836 B  3/1973  JP  48-25517  A  7 /1973  JP  54-52790  A  4/1979  JP  54-110388 A  8/1979  JP  54-119090 A  9/1979  JP  55-000027 A  1/1980 