JPS58152497A - Production of s-adenosylmethionine - Google Patents

Abstract

PURPOSE:A yeast is cultured in a medium containing methionine and a specific amine to produce S-adenosylmethionine in high yield. CONSTITUTION:At least one amine selected from polymethylenediamines such as trimethylenediamine, amino-1,2,4-triazoles such as 3-amino-1,2,4-triazole is added to a methionine-containing culture medium that contains carbon sources such as glucose, nitrogen sources, inorganic salts, and organis trace nitrients by 0.1- 2,000mg/l. Then, a yeast capable of producing S-adenosylmethionine such as Saccharmyces cerevisiae IFO2346 is inocultated to the above medium and aerobically cultured at 3-8 pH, 20-40 deg.C for 1-10 days.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing S-adenosylmethionine (hereinafter abbreviated as SAM) by a fermentation method. The present invention relates to a method for culturing yeast and efficiently producing SAM.

SAM is a substitute for fat, protein, sugar, etc. in the body.
It is an important substance involved in Therefore, the amount of RAM required these days
It has been found that it has therapeutic effects on lipidemia, hyperlipidemia, arteriosclerosis, depression and neurological psychosis, degenerative arthritis, neurological pain sensation, insomnia, etc. It is expected.

Conventionally, cultivation methods using various microorganisms have been known as methods for producing 8AM, but among them, a method using yeast is considered preferable, and a specific example thereof is the use of microorganisms of the genus Satucharomyces or the genus Ca/Dida. methods (e.g. Journal ofliacteriolog
y, vol 121.267 (1975) etc.)
, a method using microorganisms of the genus Vichia, Rhodotorula, Cryptococcus, Hansenula, Trichosporon, Frechella, Hanseniasvora, Sporobolomyces, Lipomyces, or Debaryomyces (Special Publication No. 52-1
71t No. 8) are known. However, even with these methods, the amount of SAM accumulated is not necessarily fully satisfactory, and further improvements have been desired.

Therefore, the present inventors conducted intensive studies on improving the amount of 8AM accumulated by fermentation, and found that it is effective to use a medium to which a specific compound is added together with methionine, which is a precursor of SAM. completed.

Thus, according to the present invention, in the method for producing SAM by culturing yeast capable of producing SAM in a methionine-containing medium, polymethylene diamines and amino-
Provided is a method for producing a SAM, characterized in that at least one amine selected from λa4-triazoles is present at a concentration of o, xq/I or more.

The yeast used in the present invention may be any yeast as long as it has the ability to accumulate SAM in a methionine-containing medium;
omyces) genus, Candlda
Yeasts belonging to the genus Hmnsenulm are preferred, and specific examples thereof include Satucharomyces cerevisiae IFO2346, Cantida macedoniensis IF00960, and Hansenula fabianii IF0.
1370 and the like. Furthermore, these natural and artificial mutant bacteria can be similarly used as long as they have the ability to produce 8AM.

In the present invention, it is essential that at least one amine selected from polymethylenediamines or annor-L24-) lyazoles be present in the medium in an amount of 1rI9/ or more. Specific examples of the polyalkylene diamines used include trimethylene diamine, tetramethylene diamine, spermine, spermidine, etc.
L24-) Specific examples of IJ azoles include 3-amino-24-triazole and 4-amino-L2.4-
Examples include triazole. Among these amines, trimethylene diamine, 3-amino-λ2.4-) lyazole, and spermidine are 0.1-/l-20
00~/l, preferably 1■/l~1000~/! For butrescin and spermine, it is appropriate to use 0.1q/j to 50011p/j, preferably 0.
．． It is suitable to set it to 1*/l - 200 sv/I.

In the present invention, the culture medium is prepared according to conventional methods, except for the presence of specific compounds as described above. For example, sugars such as glucose, sucrose, and fructose, organic acids such as acetic acid, hydrocarbons, alcohols such as methanol and ethanol, etc. can be used as carbon sources, and in addition, ordinary nitrogen sources, inorganic salts, organic Micronutrients are used as needed.

Cultivation is performed under good aerobic conditions, with a culture temperature of 20°C to 40°C.
A range of is preferred. When culturing, if the pH of the medium is adjusted to a range of 3 to 8, desired results can be obtained even with a normal amount. Thus, after 1 to 10 days of culture, SAM is produced and accumulated in the bacterial cells and/or the culture solution, and SAM can be obtained by treating this in a conventional manner.

For example, extract the upper body containing SAM with chloric acid, neutralize the extract with potassium hydrogen carbonate while cooling with water, contact with a strongly acidic cation exchange resin as necessary, then adsorb SAM, and then elute with sulfuric acid. , SAM can be isolated by adding phosphotungstic acid to the eluate to precipitate it.

The present invention will be described in more detail with reference to Examples below, but the present invention is not limited thereto.

Example L Glucose 5ildi, Polypebut:, to, s
i/dl.

KH*PQ, 0.411/d1. K4HP060.
41/di, Mg5(i-7H*00.02j'/d
l, yeast extract 0. One platinum loop of Saccharomyces cerevisiae IF02346 grown for 2 days on an agar slant medium (pH 6,0) consisting of saccharose 101/d1. Force fj / acid 19/d
i', Trison (Bact.

tryptone) 111 /d1. 0 to KHaP
．． 41/di, K, 111/dl to HP, Mg5C
k-7 00.049/di, L-methionine 0.
The medium 5ajK, which was made of 7517 dl and a predetermined amount of amines shown in Table 1, adjusted to pH 6.6, and sterilized by heat, was inoculated and shaken at 28° C. for 5 days. Then, the amount of 81M accumulated was measured and the results are shown in Table 1.

Table 1 This product was added to the medium aseptically at room temperature without heat sterilization.

Example 2 Culture was carried out under the same conditions as in Example 1, except that the strains shown in Table 2 were used in place of Saccharomyces cerevisiae IF0234g, and 10~/j of various amines were added to the medium.

The results are shown in Table 2.

Table 2 Car 1 was added to the medium aseptically at room temperature without being heat sterilized.

Patent applicant: Zeon Corporation

Claims (1)

[Claims] In a method for producing 8-adenosylmethionine by culturing yeast capable of producing LS-adenosylmethionine in a methionine-containing medium, at least one selected from polymethylenediamines and amino-λ44-triazoles is added to the medium. A method for producing S-adenosylmethionine, characterized in that an amine is present at a concentration of 0.1 wg/j or more.