CH645607A5 - METHOD FOR THE MICROBIOLOGICAL PRODUCTION OF CO ENZYME Q. - Google Patents

Description

The present invention relates to a method for producing co-enzyme Q of the formula I.

H3CO.

HJCO

O

A.

CH:

(I)

CH2-CH = C -CHz-KflH CHs in which n has a value of 1-10, microbiologically.

As can be seen from the formula I, the co-enzymes Q, also called ubiquinones, are 2,3-bimethoxy-5-methyl-1,4-benzoquinones, which contain an isoprene side chain in the 6-position of the quinone nucleus.

If in the co-enzyme Q of the above general formula I, n has a value of 8, then it is the co-enzyme Qs.

If the number 9 in the general formula n given above stands for 5, then it is the co-enzyme Q9.

If n has the value 10 in the general formula given above, then it is the co-enzyme Qio-

Co-enzyme Q is common in animals, plants, microorganisms and the like, and it plays an important role as a constitutive element of the terminal electron transfer system.

It has recently been found that Co-enzyme Q has excellent medical and physiological effects in the treatment of various pathological conditions. In particular, the co-enzyme Q10 is regarded as a very special valuable medicinally usable agent because the co-enzyme Q of humans is the co-enzyme Q10.

20 The co-enzyme Q can be obtained by extracting it from animal or vegetable tissues or from microorganisms, or by chemically synthesizing it. However, it is difficult to produce co-enzyme Q by extracting it from animal or vegetable tissues to a large extent. Furthermore, it is also difficult to produce co-enzyme Q by organic synthesis, because in this case the yields are unfavorable. For this reason, all of the above processes are unsatisfactory if one wishes to produce a coenzyme Q on an industrial scale. On the other hand, if one wants to produce the co-enzyme Q by a working process for the extraction of microorganisms, then there is of course the possibility that this process can be used in an economical manner because possibly higher yields of cells 35 and accordingly higher yields of co-enzyme Q can be obtained.

It is also known that microorganisms belonging to the genus Pseudomonas are able to form the co-enzymes Q8, Qt, and Q10.

The aim of the present invention was therefore to find out those compounds which are able to lead to a significant increase in the content of co-enzyme Q per cell unit when these compounds in question are added to the growth medium, in comparison to 45 amount formed if these compounds in question are not contained in the growth medium.

It is known that p-hydroxybenzoic acid as well as acetic acid and its salts are able to increase the content of co-enzyme Q per cell unit when this compound is added to a growth medium. In this connection, reference should be made to Japanese Patent Publication No. 20 396/1972. Furthermore, it is also known that the isoprene side chain is formed in the biosynthesis via the geranyl pyrophosphate and the farnesyl pyrophosphate, the condensation of isopentenyl pyrophosphate and dimethyl allyl pyrophosphate being repeated in this biosynthesis . However, since these precursors in the biosynthesis are difficult to migrate through the cell membrane, no one had previously attempted to add such precursors to a culture medium in order to increase the content of co-enzyme Q.

It has now surprisingly been found that if a microorganism from the genus 65 Pseudomonas, which is able to form the co-enzyme Q, is cultured in a growth medium, the yield of the desired product can be increased significantly by certain substances are added to the culture medium.

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The present invention therefore relates to a process for the preparation of co-enzyme Q of the formula I.

H3CO.

CH3

(I)

HaCO - ^^ Y ^ CHz-C ^ C "CH2" hiH

0

CH:

wherein n has a value of 1-10, which is characterized in that a microorganism from the genus Pseudomonas, which is able to form the co-enzyme Q, is grown in a growth medium to which at least one compound is made is added to the group of compounds which comprises the following compounds: isopentenyl alcohol, dimethyl allyl alcohol, geraniol, isopentenyl acetate, dimethyl allyl acetate, Gernyl acetate and β-methylcrotonic acid and the co-enzyme Q formed is obtained .

Co-enzyme Qs, co-enzyme Q9 and co-enzyme Q10 are preferably produced by the process according to the invention, since these co-enzymes Q are important from an economic point of view.

It was found that the above-mentioned compounds of the genus Pseudomonas added to the growth medium in the process according to the invention are easily consumed and that these compounds are able to significantly increase the content of co-enzyme Q per cell unit.

Any microorganisms that are able to form co-enzyme Q can be used to carry out the method according to the invention.

An example of a microorganism that is able to form co-enzyme Qi0 is the microorganism Pseudomonas diminuta, which is available from the American Type Culture Collection (ATCC), 12 301 Parklawn Drive, Rockville, Maryland 20 852 - USA July 7, 1953 is deposited with the accession number ATCC 11 568. This microorganism was also deposited with the Institute of Applied Microbiology (IAM), 1-1,1-chome, Yayoi, Bunkyo-ku, Tokyo 113 with the accession number IAM 1513. However, other microorganisms can also be used when carrying out the process according to the invention for producing co-enzyme Q10.

Examples of microorganisms that are able to form co-enzyme Qo are, for example, Pseudomonas schuyl-killiensis, available from the American Type Culture Collection (ATCC), 12 301 Parklawn Drive, Rockville, Maryland 20 852 - USA - on July 20 1978 with the accession number ATCC 31 419 (this microorganism was also deposited with the Institute of Applied Microbiology (IAM), Tokyo University, Tokyo, Japan with the accession number IAM 1126), and Pseudomonas denitrificans, which are deposited with the American Type Culture Collection ( ATCC), 12 301 Parklawn Drive, Rockville, Maryland - USA - on June 30, 1960 with the accession number ATCC 13 867 (this microorganism was also registered at the Institute of Applied Microbiology (IAM) Tokyo University, Tokyo, Japan, with the IAM 12 023) and Pseudomonas olevorans, available from the American Type Culture Collection (ATCC), 12 301 Parklawn Drive, Rockville, Maryland 20 852 - US A - was deposited on April 17, 1941 with the accession number ATCC 8062 (this microorganism

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mus has also been deposited at the Institute of Applied Microbiology (IAM), Tokyo University, Tokyo, Japan with the accession number IAM 1508), as well as Pseudomonas putrefaciens, which are with the American Type Culture Col-5 lection (ATCC), 12 301 Parklawn Drive, Rockville, Maryland 20 852 - USA - with the accession number ATCC 8071. This deposit of microorganisms could be obtained from the depository in question before September 1977 on request. The frag-10 microorganism is also deposited with the Institute of Applied Microbiology (IAM) with the accession number IAm 1509. Further, similar microorganism strains can also be used when carrying out the process according to the invention for producing co-enzyme Q9.

Microorganisms that are able to form co-enzyme Q8 are, for example, Pseudomonas rubescens, which are available from the American Type Culture Collection (ATCC), 12 301 Parklawn Drive, Rockville, Maryland 20 852 - USA - on March 10, 1955 the deposit number ATCC 12 099 (this microorganism was also deposited with the Institute of Applied Microbiology (IAM), Tokyo University, Tokyo, Japan with the deposit number IAM 1510), Pseusomonas fulva, which is deposited with the Ame-25 rican Type Culture Collection ( ATCC), 12 301 Parklawn Drive, Rockville, Maryland 20 852 - USA - on July 20, 1978 with the accession number ATCC 31 418 (this microorganism was also registered with the Institute of Applied Microbiology (IAM), Tokyo University, Tokyo, Ja- 30 pan with the accession number IAM 1529), as well as Pseudomonas putida, with the American Type Culture Collection (ATCC) 12 301 Parklawn Drive, Rockville, Maryland 20 852 - USA - with the accession number ATCC 4359 was deposited. This microorganism-35 strain could be freely obtained from the American Type Culture Collection before September 1977 on request. The microorganism in question is also deposited at the Institute of Applied Microbiology (IAM) with the deposit number IAm 1506. Other similar 40 microorganisms can also be used to produce co-enzyme Qs by the process according to the invention.

In the growth medium used to carry out the method according to the invention, can. 45 types of sugar, such as glucose, molasses and the like, and any other such materials can be used as substances which provide the carbon for the microorganisms. Such materials can thus be used as carbon sources in the culture medium. Inorganic nitrogen compounds, such as ammonium sulfate, ammonium chloride and the like, and also organic nitrogen-containing compounds, such as corn steep liquor, fish meat extracts, peptones, yeast extracts and the like, can be used as material which provides the nitrogen necessary for the microorganisms, so as nitrogen sources. In addition, materials such as potassium salts, sodium salts, magnesium salts, salts of phosphoric acid and sulfuric acid 60 can be used as organic salts, ie as suppliers of minerals.

The cultivation of the microorganisms is generally carried out by stirring with exposure to air and while maintaining a pH in the range of 4-8, the cultivation temperature being generally in the range 65 of 25-35 ° C., and the cultivation time generally 10-50 Hours.

The addition of isopentenyl alcohol, dimethyl allyl alcohol to be carried out in the process according to the invention,

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Geraniol, isopentenyl acetate, dimethyl allyl acetate, geranyl acetate and β-methyl crotonic acid can be used in a suitable manner, i.e. by a desired addition method and at a desired time. For example, the entire amount of this additive can be added at the beginning of the cultivation, or at any desired stage of growth of the microorganism during the cultivation, or the total amount can be gradually added by small additions, for example according to the state of the fermentation. It is also possible to add the additive according to the invention as a single additive or in combination with other additives. The amount of additive to be made in the process according to the invention is usually in the range from 1 x 10-s to 5 x 10 "3 mol additive per liter, based on the final concentration, and in particular the amount is in the range of 5 x 10 "5 to 5 x 10 ~ 4 moles per liter of growth medium.

After cultivation, the co-enzyme Q formed is extracted from the cells and separated from the other materials. For example, the wet cells obtained by centrifugation can be extracted using a hydrophilic solvent such as acetone or the like. A fraction containing the co-enzyme Q is then placed in a solvent such as petroleum ether or the like. The fraction containing the co-enzyme Q is then subjected to a fractional purification, for example using aluminum oxide or the like, in which case the co-enzyme Q can then be isolated.

When carrying out the method according to the invention, the identification of the coenzyme Q was carried out by comparing the product produced by the method according to the invention with a standard sample with the aid of the UV spectrum and determining the melting point, and by carrying out thin-layer chromatography with the reverse phase , in which a mixture of acetone + water in a mixing ratio of 95: 5 was used as the solvent system, and by carrying out further identification.

The invention will now be explained in more detail with reference to the following examples:

example 1

In a fermentation container with a capacity of 30 liters, 15 liters of a growth medium were added, which had a pH of 7.0. This growth medium contained the following ingredients in the amounts indicated:

Component quantity in%

KH2P04 0.05

Na2HP04 0.15

MgS04-7H20 0.05

Glucose 1.0

Peptone 1.0

Yeast extract 0.2

The contents were then sterilized with steam and 645 mg of isopentenyl alcohol, dissolved in 10 ml of ethanol, were added. Subsequently, Pseudomonas schuylkilliensis, which is deposited with the American Type Culture Collection USA with the accession number ATCC 31419 and with the Institute of Applied Microbiology, Tokyo, has the accession number IAM-1126, and which previously was in 500 ml of a culture medium of the same composition as it was was cited above for 24 hours, inoculated into the growth medium described above, and cultured for 24 hours with aeration at a temperature of 27 ° C. Aeration was carried out by blowing 15 liters of air per minute.

After this period, the culture broth was centrifuged off to obtain 418 g of wet cells, which corresponded to 87 g of dry cells.

2 liters of acetone were added to the wet cells and extracted with stirring. The cells were then separated by centrifugation. This procedure was repeated two more times. The acetone extracts thus obtained were combined and concentrated under reduced pressure to distill off the acetone. The remaining solution was then extracted three times with 1 liter of petroleum ether and the petroleum ether layers thus obtained were combined. The petroleum ether phase thus obtained was washed with water, dried and then concentrated under reduced pressure. An oil remained as a residue, which was dissolved in a small amount of petroleum ether and then subjected to chromatography on aluminum oxide. In this chromatography, a mixture of petroleum ether and ethyl ether was used as the eluent.

The solvent was distilled off from the eluate thus obtained, which contained the co-enzyme Q. The remaining oil was dissolved in a small amount of ethanol and left to stand in a refrigerator, where crystals separated from Co-enzyme Q9. These crystals were recrystallized three times from ethanol to obtain 142.6 mg of crystals of Co-enzyme Q9.

On the other hand, the same cultivation as described above was carried out using 15 liters of a culture medium of the same composition, but to which no isopentenyl alcohol had been added. In the same way as described above, 359 g of wet cells were obtained, corresponding to 69 g of dry cells. Subsequently, the same working procedures as described above were carried out, but in this case only 81.42 mg of crystals of the co-enzyme Q9 were obtained.

The effect of isopentenyl alcohol on the formation of co-enzyme Qg was calculated on the basis of the above results. By adding the isopentenyl alcohol to the broth, the yield of Co-enzyme Q9 per liter of broth could be increased by 75%, and per liter of dry cells by 39%. From these results it can clearly be seen that the addition of isopentenyl alcohol can effectively increase the yield of co-enzyme Q9 formed.

Example 2

The procedure of Example 1 was repeated except that now 1.16 g of geraniol was added in place of the isopentenyl alcohol. This growth method gave 390 mg of wet cells, corresponding g of dry cells. The wet cells thus obtained were subjected to the same procedures described in Example 1 to obtain 104.7 mg of crystals of the co-enzyme Q9.

For comparison purposes, the same microorganism was grown using a growth medium of the same composition but to which no geraniol had been added. This gave 327 g of wet cells, corresponding to 63 g of dry cells. 74.3 mg of crystals of the co-enzyme Q9 were obtained from these cells.

Based on the above results, the effectiveness of geraniol on the formation of the co-enzyme was determined

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Qg calculated. It was found that by adding the geraniol to the growth medium, the yield of the co-enzyme Q9 per liter of the broth could be increased by 41% and increased by 30% per gram of the dry cells.

Example 3

The microorganism Pseudomonas rubescens, which is deposited with the American Type Culture Collection under the accession number ATCC 12 099 and with the Institute of Applied Microbiology, Tokyo under the accession number IAM-1510, was grown in the same growth medium and grown in the same way, as described in Example 2. This gave 410 g of wet cells, corresponding to 73 g of dry cells. These cells were treated in the same manner as described in Example 1 to obtain 58.4 mg of the co-enzyme Q8.

On the other hand, for comparison purposes, the same microorganism was grown in the same growth medium, except that no geraniol was added now. This gave 390 g of wet cells, corresponding to 74 g of dry cells. 44.4 mg of the co-enzyme Q8 were obtained from these cells.

Based on the above results, the same comparison was again made as described in Example 1. It can be seen from this that by adding geraniol to the culture medium, the yield of the co-enzyme Qg per liter of broth could be increased by 32% and per gram of dry cells by 33%.

Example 4

The microorganism Pseudomonas diminuta, which is deposited with the American Type Culture Collection with the number ATCC 11 568 and with the Institute of Applied Microbiology, Tokyo with the number IAM-1513, was cultivated according to the same working method as that in Example 1 with the exception that sodium acetate was now contained in the growth medium formulation instead of glucose. Furthermore, the difference from Example 1 was also that three fractions of 300 ml each of the isopentenyl alcohol were added separately, ie a total of 900 mg.

This procedure gave 380 g of the wet cells, corresponding to 69 g of dry cells, and these were then subjected to the same treatments described in Example 1. This gave 30.5 mg of crystals of the co-enzyme Q10.

On the other hand, the same microorganism was grown in a culture medium to which no isopentenyl alcohol had been added, and 320 g of wet cells were obtained, corresponding to 61 g of dry cells. From this material, 19.8 mg of crystals of the co-enzyme Q10 were obtained.

On the basis of the results given above and using the same comparisons which were also made in Example 1, it was found that the addition of the isopentenyl alcohol increased the yield of the co-enzyme Q10 per liter of the broth by 54.0% and the increase in yield per gram of dry cells was 38%.

Example 5

The procedure described in Example 1 was carried out, with the exception that the microorganism Pseudomonas denitrificans, which is used in the American Type

Culture Collection with the number ATCC 13 867, and at the Institute of Applied Microbiology, Tokyo, under which the number IAM-12 023 is deposited. Furthermore, the method used here differed from that of Example 1 in that two portions, each containing 1 g of geraniol, were added separately to the growth medium, ie a total of 2 g. The addition took place at different times during the breeding. In this procedure, 395 g of wet cells were obtained, corresponding to 76 g of dry cells, and the cells thus obtained were then subjected to the same treatment procedures as described in Example 1. This gave 63.1 mg of crystals of the co-enzyme Q9.

On the other hand, the same microorganism was grown in a culture medium to which no geraniol had been added. This gave 328 g of wet cells, corresponding to 63 g of dry cells. From these, 37.2 mg of the co-enzyme Q9 were obtained.

Based on the results given above, the same comparison of results was made as explained in Example 1. It can be seen that the addition of the geraniol increased the yield of the co-enzyme Q9 per liter of the broth by 69%, and the increase in the yield per gram of dry cells was 41%.

Example 6

The working procedure of Example 1 was carried out, with the exception that the microorganism Pseudomonas fulva, which has the accession number ATCC 31 418 from the American Type Culture Collection and the IAM-1529 number from the Institute of Applied Microbiology, Tokyo, is now deposited. has been used. The procedure used here also differed from Example 1 in that three portions of 1 g each of isopentenyl alcohol were added separately at different times during the cultivation, that is to say a total of 3 g. 390 g of wet cells were obtained, corresponding to 73 g of dry cells, and these were then subjected to the same treatment described in Example 1. This gave 86.4 mg of crystals of the coenzyme Q8.

On the other hand, the same microorganism was grown in a culture medium to which no isopentene alcohol was added. In this case, 350 g of wet cells were obtained, corresponding to 67 g of dry cells. From these, 60.5 mg of crystals of the co-enzyme Q8 were obtained.

On the basis of the above results, a comparison of the results was carried out as described in Example 1. It can be seen that the addition of the isopentenyl alcohol increased the yield of the co-enzyme Qg per liter of the broth by 43%, and the increase in the yield per gram of dry cells was 31%.

Example 7

The procedure described in Example 1 was repeated, except that the microorganism Pseudomonas rubescens, which is deposited with the American Type Culture Collection with the accession number ATCC 12 099 and with the Institute of Applied Microbiology, Tokyo, with the number IAM-1510 was used, and that in this case 645 mg of dimethyl allyl alcohol were added to the growth medium. 430 g of wet cells were obtained, corresponding to 80 g of dry cells, and these were treated as described in Example 1

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is. This gave 86 mg of crystals of the coenzyme Q8.

On the other hand, the same microorganism was grown in the corresponding culture medium, but in this case no dimethyl allyl alcohol was added. This gave 390 g of wet cells, corresponding to 76 g of dry cells. 68 mg of crystals of the co-enzyme Q8 were obtained from these cells.

Based on the above results, the same comparisons were made as in Example 1. From this it can be seen that the addition of the dimethyl allyl alcohol increased the yield of the co-enzyme Q8 per liter of the broth by 26%, and the increase in the yield per gram of dry cells was 20%.

Example 8

The procedure described in Example 1 was repeated, except that Pseudomonas fulva, which has the accession number ATCC 31 418 at the American Type Culture Collection and the accession number IAM-1529 at the Institute of Applied Microbiology, Tokyo, is now used as the microorganism has been. Furthermore, 750 mg of β-methyl-crotonic acid were now added to the growth medium. This gave 540 g of wet cells, corresponding to 105 g of dry cells, and these cells were subjected to the same treatments which are explained in Example 1. In this way, 102 mg of crystals of the co-enzyme Qa were obtained.

On the other hand, the same microorganism was grown in the same culture medium, but now no ß-methyl-crotonic acid was added. This gave 525 g of wet cells, corresponding to 103 g of dry cells, and 79 mg of crystals of the coenzyme Q8 were obtained from these cells.

Based on the above results, the same comparison of results as that described in Example 1 was made. It was found that the addition of β-methyl-crotonic acid increased the yield of the co-enzyme Q8 per liter of the broth by 28%, and the increase in the yield per gram of dry cells was 26%.

Example 9

The procedure of Example I was repeated, with the exception that the microorganism Pseudomonas olevorans, which is deposited with the American Type Culture Collection with the number ATCC 8062 and with the Institute of Applied Microbiology, Tokyo with the number IAM-1508, has been used. Furthermore, the procedure also differed from that of Example 1 in that 960 mg of dimethyl allyl acetate were now added. This gave 490 g of wet cells, corresponding to 94 g of dry cells, and these were subjected to the same treatment described in Example 1. 96 mg of crystals of the co-enzyme Qg were obtained.

On the other hand, the same microorganism was grown in a culture medium to which no dimethyl allyl acetate was added this time. This gave 470 g of wet cells, corresponding to 90 g of dry cells, and. 68 mg of crystals of the co-enzyme Q9 were obtained from this material.

The same comparison made in Example 1 was made based on the above results. It can be seen that the addition of the dimethyl allyl acetate increased the yield of the co-enzyme Q9 per liter of the broth by 42%, and the increase in the yield per gram of dry cells was 34%.

Example 10

5 The procedure described in Example 1 was repeated, with the exception that now as the microorganism Pseudomonas schuylkilliensis, which has the accession number ATCC 31 419 from the American Type Culture Collection, and from the Institute of Applied Microbiology, Tokyo, io with the number IAM- 1126 was deposited, was used. Furthermore, 1.47 g of geranyl acetate were now added to the growth medium. This gave 530 g of wet cells, corresponding to 93 g of dry cells, and these were subjected to the same treatment as described in Example 15 1. This gave 120 mg of crystals of the co-enzyme Qg.

For comparison purposes, the same microorganism was grown in the same growth medium, but no geranyl acetate was now added. Thereby, 525 g of wet cells * corresponded to 90 g of dry cells and 98 g of crystals of the co-enzyme Q9 were obtained from these cells.

Based on the above results, the same comparison was made as in Example 1. By adding the geranyl acetate, the yield of the co-enzyme Q9 per liter of broth was increased by 23%, and the increase in the yield per gram of dry cells was 19%.

30 Example 11

The procedure described in Example I was again followed, with the exception that the microorganism Pseudomonas denitrifîcans used, which has the deposit number 35 ATCC 13 867 from the American Type Culture Collection, and the number from the Institute of Applied Microbiology, Tokyo, with the number IAM -12 023 is used. Furthermore, the growth medium used differed from that used in Example I in that a mixture of 960 mg of isopentenyl-40 acetate and 1.47 g of geranyl acetate was now added. This gave 480 g of wet cells, corresponding to 96 g of dry cells. These cells were subjected to the same treatment described in Example I. This gave 115 mg of crystals of the co-enzyme Q9. 45 In a comparative experiment, the same microorganism was grown in a growth medium, but to which no mixture of isopentenyl acetate and geranyl acetate was added. 490 g of wet cells were obtained, corresponding to 98 g of dry cells. From this, 76 mg of crystals of the co-enzyme Q9 were obtained.

Based on the above results, the same comparison was made as in Example 1. By adding the mixture of isopentenyl acetate and geranyl acetate, the yield of the co-enzyme Q9 per liter of the culture medium was increased by 51%, and per gram of dry cells by 54%.

Example 12

The same cultivation procedure was carried out, 6o as in Example 4, with the exception that the microorganism Pseudomonas diminuta, which has the accession number ATCC 11 568 from the American Type Culture Collection, and the number from the Institute of Applied Microbiology, Tokyo IAM-I5I3 is deposited, has now been bred by adding a mixture of 960 mg of isopentenyl acetate and 960 mg of dimethyl allyl acetate. 495 g of wet cells were obtained, corresponding to 98 g of dry cells. These were given the same treatment

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subjected to that described in Example 1, whereby 53 mg of crystals of the co-enzyme Q10 were obtained.

On the other hand, the same microorganism was grown in a growth medium, but this time the mixture of isopentenyl acetate and dimethyl allyl acetate was not added. This gave 480 g of wet cells, corresponding to 94 g of dry cells. 39 mg of crystals of the co-enzyme Q10 were obtained from this material.

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Based on the above results, the same comparison was made as that made in Example 1. It was seen from this that the addition of the isopentenyl acetate and the dimethyl allyl acetate increased the yield of the co-enzyme Qi0 per liter of broth by 36%. The increase in the yield per gram of dry cells was 32%.

s

Claims (4)

645 607 PATENT CLAIMS 1. Process for the preparation of Co-enzyme Q of Formula I CH3 CH2-CH = C -CH2 -) - nH In CHs (I) wherein n has a value of 1-10, characterized in that a microorganism from the genus Pseudomonas, which is able to form the co-enzyme Q, is grown in a growth medium to which at least one compound from the group of Compounds comprising the following compounds: isopentenyl alcohol, dimethyl allyl alcohol, geraniol, isopentenyl acetate, dimethyl allyl acetate, Gernyl acetate and β-methyl-crotonic acid are added and the co-enzyme Q formed is recovered. 2. The method according to claim 1, characterized in that the microorganism used is Pseudomonas diminuta with the deposit number at the American Type Culture Collection ATCC 11 568, and that the co-enzyme Q formed is the co-enzyme QI0. 3. The method according to claim 1, characterized in that the microorganism used is Pseudomonas schuylkilliensis with the accession number ATCC 31 419, Pseudomonas denitrificans with the accession number ATCC 13 867 or Pseudomonas olevorans with the accession number ATCC 8062, and that the co-enzyme Q is Co-enzyme is Q9. 4. The method according to claim 1, characterized in that the microorganism used is Pseudomonas rubescens with the accession number ATCC 12 099 or Pseudomonas fulva with the accession number ATCC 31 418, and that the co-enzyme Q formed is the co-enzyme Q8.