Processes for producing coenzyme Q10

Patent metadata

Field	Value
Publication number	US-9315839-B2
Application number	US-201113020500-A
Country	US
Kind code	B2
Filing date	Feb 3, 2011
Priority date	Dec 27, 2001
Publication date	Apr 19, 2016
Grant date	Apr 19, 2016

Abstract

The present invention relates to a process for producing reduced coenzyme Q 10 which comprises obtaining microbial cells containing reduced coenzyme Q 10 at a ratio of not less than 70 mole % among the entire coenzymes Q 10 , optionally disrupting the cells and recovering thus produced reduced coenzyme Q 10 . The present invention also relates to a process for producing oxidized coenzyme Q 10 which comprises either recovering oxidized coenzyme Q 10 after oxidizing the above-mentioned microbial cells or disrupted product thereof, or recovering reduced coenzyme Q 10 from the above-mentioned microbial cells or disrupted product thereof to oxidize thus-obtained reduced coenzyme Q 10 thereafter. According to the processes of the present invention, reduced coenzyme Q 10 and oxidized coenzyme Q 10 can be produced simply on the industrial scale.

First claim

The invention claimed is:

1. A process for producing the reduced coenzyme Q 10 represented by the following formula (I):

which comprises culturing reduced coenzyme Q 10 -producing microorganisms in a culture medium containing a carbon source, a nitrogen source, a phosphorus source and a micronutrient 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 extracting the reduced coenzyme Q 10 by an organic solvent under the condition that the reduced coenzyme Q 10 is protected from an oxidation reaction, to thereby obtain an extract containing not less than 70 mole % reduced coenzyme Q 10 among the entire coenzymes Q 10 , and
wherein the condition that the reduced coenzyme Q 10 is protected from an oxidation reaction is selected from the group consisting of an atmosphere of inert gas, a high salt concentration condition where inorganic salts are contained in not less than about 5% in an aqueous phase, the condition in the presence of not less than 0.1 mole % of a strong acid with a pKa value of not more than 2.5 relative to 1 mole of reduced coenzyme Q 10 , the condition in the presence of ascorbic acid, citric acid or salts and esters thereof, and the condition in the presence of dithionous acid.

2. The process according to claim 1 , wherein the culture is carried out at 15 to 45° C. and at a pH of 4 to 9.

3. The process according to claim 1 ,
wherein the concentration of the carbon source in the culture is controlled to a concentration that no adverse effects are substantially caused on the productivity of reduced coenzyme Q 10 .

4. The process according to claim 1 ,
wherein the extraction of reduced coenzymes Q 10 is carried out from wet cells or dry cells of the microbial cells or disrupted product thereof by using a hydrophilic organic solvent.

5. The process according to claim 1 ,
wherein the extraction of the reduced coenzymes Q 10 is carried out from an aqueous suspension of the microbial cells or disrupted product thereof by using a hydrophobic organic solvent.

6. The process according to claim 5 ,
wherein the hydrophobic organic solvent is a hydrocarbon, a fatty acid ester or an ether.

7. The process according to claim 5 ,
wherein the hydrophilic organic solvent is used as an auxiliary solvent in combination with the hydrophobic organic solvent.

8. The process according to claim 7 ,
wherein the hydrophobic organic solvent is a hydrocarbon, and the hydrophilic organic solvent is an alcohol.

9. The process according to claim 7 ,
wherein the extraction is carried out under the condition that the hydrophobic organic solvent is contained in 25 to 65% by volume and the hydrophilic organic solvent is contained in 5 to 50% by volume.

10. The process according to claim 1 ,
wherein the reduced coenzyme Q 10 -producing microorganisms have not less than 1 μg/mL of a productivity of reduced coenzyme Q 10 per unit culture medium when measured by HPLC.

11. The process according to claim 10 ,
wherein the microorganisms are microorganisms of the genus Agrobacterium , the genus Aspergillus , the genus Acetobacter , the genus Aminobacter , the genus Agromonas , the genus Acidiphilium , the genus Bulleromyces , the genus Bullera , the genus Brevundimonas , the genus Cryptococcus , the genus Chionosphaera , the genus Candida, the genus Cerinosterus , the genus Exisophiala , the genus Exobasidium , the genus Fellomyces , the genus Filobasidiella , the genus Filobasidium , the genus Geotrichum , the genus Graphiola , the genus Gluconobacter , the genus Kockovaella , the genus Kurtzmanomyces , the genus Lalaria , the genus Leucosporidium , the genus Legionella , the genus Methylobacterium , the genus Mycoplana , the genus Oosporidium , the genus Pseudomonas , the genus Psedozyma , the genus Paracoccus , the genus Petromyces , the genus Rhodotorula , the genus Rhodosporidium , the genus Rhizomonas , the genus Rhodobium , the genus Rhodoplanes , the genus Rhodopseudomonas , the genus Rhodobacter , the genus Sporobolomyces , the genus Sporidiobolus , the genus Saitoella , the genus Schizosaccharomyces , the genus Sphingomonas , the genus Sporotrichum , the genus Sympodiomycopsis , the genus Sterigmatosporidium , the genus Tapharina , the genus Tremella , the genus Trichosporon , the genus Tilletiaria , the genus Tilletia , the genus Tolyposporium , the genus Tilletiopsis , the genus Ustilago , the genus Udeniomyces , the genus Xanthophilomyces , the genus Xanthobacter , the genus Paecilomyces , the genus Acremonium , the genus Hyhomonus , or the genus Rhizobium.

12. The process according to claim 1 ,
wherein the production amount of reduced coenzyme Q 10 on completion of the culture is not less than 1 μg/mL.

13. The process according to claim 3 ,
wherein the culture is carried out by a fed batch culture method.

14. The process according to claim 13 ,
wherein the carbon source is supplied to the culture medium separately from other components.

15. The process according to claim 1 ,
wherein, as the organic solvent to be used for extraction of reduced coenzyme Q 10 , at least one species of hydrocarbons, fatty acid esters, ethers and nitriles is used.

16. The process according to claim 4 ,
wherein the hydrophilic organic solvent is acetone, acetonitrile, methanol, ethanol, 1-propanol or 2-propanol.

17. The process according to claim 7 ,
wherein the hydrophobic organic solvent is an aliphatic hydrocarbon, and the hydrophilic organic solvent is a monohydric alcohol containing 1 to 5 carbon atoms.

18. The process according to claim 7 ,
wherein the hydrophobic organic solvent is at least one species of hexane and heptane, and the hydrophilic organic solvent is at least one species of methanol, ethanol, 1-propanol and 2-propanol.

19. The process according to claim 5 ,
wherein the extraction is carried out by continuous extraction.

20. The process according to claim 1 ,
wherein the obtained reduced coenzyme Q 10 is purified optionally and crystallized to obtain a reduced coenzyme Q 10 crystal.

21. The process according to claim 1 ,
which further comprises, before the step of extracting the reduced coenzyme Q 10 , disrupting the microbial cells under the condition that the reduced coenzyme Q 10 is protected from an oxidation reaction.

22. The process according to claim 21 ,
wherein the cell disruption is carried out by a physical treatment.

23. The process according to claim 22 ,
wherein the physical treatment is carried out by a high pressure homogenizer, an ultrasonic homogenizer, a French press or a ball mill.

24. The process according to claim 21 ,
wherein the cell disruption is carried out under an acidic to a weakly basic condition.

Assignees

• Yajima Kazuyoshi
• Kato Takahisa
• Kanda Akihisa
• Kitamura Shiro
• Ueda Yasuyoshi
• Kaneka Corp

Inventors

• Yajima Kazuyoshi
• Kato Takahisa
• Kanda Akihisa
• Kitamura Shiro
• Ueda Yasuyoshi

Classifications

• C12P7/66 Primary

  containing the quinoid structure · CPC title

• C12P7/22 Primary

  aromatic · CPC title