US3223592A - Production of 5'-nucleotides - Google Patents
Production of 5'-nucleotides Download PDFInfo
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- US3223592A US3223592A US756541A US75654158A US3223592A US 3223592 A US3223592 A US 3223592A US 756541 A US756541 A US 756541A US 75654158 A US75654158 A US 75654158A US 3223592 A US3223592 A US 3223592A
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- nucleotides
- monophosphate
- ribonucleic acid
- phosphodiesterase
- inosine
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
- C12P19/30—Nucleotides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/14—Fungi; Culture media therefor
- C12N1/16—Yeasts; Culture media therefor
- C12N1/18—Baker's yeast; Brewer's yeast
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
- C12P19/30—Nucleotides
- C12P19/32—Nucleotides having a condensed ring system containing a six-membered ring having two N-atoms in the same ring, e.g. purine nucleotides, nicotineamide-adenine dinucleotide
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
- C12P19/30—Nucleotides
- C12P19/34—Polynucleotides, e.g. nucleic acids, oligoribonucleotides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/803—Physical recovery methods, e.g. chromatography, grinding
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/8215—Microorganisms
- Y10S435/911—Microorganisms using fungi
- Y10S435/933—Penicillium
Definitions
- This invention relates to a process for producing the solution containing 5'-nucleotides (adenosine-5'-monophosphate, guanosine-5-monophosphate, uridine-5'-monophosphate, cytidine-5-monophosphate, inosine-5'-monophosphate, xanthosine-5'monophosphate) from ribonucleic acid by microbial 5-phosphodiesterase action, and to an application of the 5'-nucleotides as special seasonings.
- 5'-nucleotides adenosine-5'-monophosphate, guanosine-5-monophosphate, uridine-5'-monophosphate, cytidine-5-monophosphate, inosine-5'-monophosphate, xanthosine-5'monophosphate
- the object of this invention is to produce flavorous 5-nucleotides, which were so far prepared generally only by organic synthesis or by extraction from tissues of various organisms such as mammalian muscle, eco nomically and in good yield from ribonucleic acid, using the enzymes of microorganisms.
- the present invention provides a process for the production of 5-nucleotides which is characterized in this that ribonucleic acid is degraded into 5'-nucleotides by 5'-phosphodiesterase which is contained in living cells, dry cells, culture filtrates or cell extracts of microorganisms described above.
- the microorganisms containing 5-phosphodiesterase are able to be grown on either solid media or liquid media. For economical mass production, however, liquid media are more appropriate.
- the conventional carbon and nitrogen sources and several inorganic salts may be employed effectively.
- This invention includes both one step method and two step method. In one step method, both growing of microorganism and enzymic degradation of ribonucleic acid are carried out simultaneously, em-
- Patented Dec. 14, 1965 ploying culture medium containing ribonucleic acid.
- growing of microorganism and enzymic degradation of ribonucleic acid are carried out separately.
- Crude solution containing ribonucleic acid such as yeast extracts, may be used as an appropriate starting material.
- microbial cells cultivated for producing 5- phosphodiesterase are effectively utilized too as a source of ribonucleic acid.
- Free 5'-nucleotides or their alkali salts obtained by the processing as described above enhance or increase the flavor of the foods, beverages, and seasonings in which they are placed. This flavoring action is caused by the synergy between 5-nucleotides and amino acids or organic acids.
- purine and pyrimidine bases, their nucleosides, and their 2'- and 3-nucleotides have little flavor, while 5'-nucleotides, especially inosine-S'-monophosphate, guanosine-5-monophosphate, and xanthosine-S'-monophosphate, have very agreeable good taste.
- This invention relates also to the application of 5'- nucleotides based on the utilization of aforesaid synergy between 5-nucleotides and amino acids or organic acids.
- the application of 5 -nucleotides according to the present invention comprises adding one or more of 5-nucleotides to general foods or beverages such as meat products, soups, roux, vinegar, various dressings, sauces, curry powder and various drinks including wine, to counteract the displeasing pungency which spoils the taste qualities of foods or beverages, and to enhance or increase the flavor specifically according to the synergy between 5-nucleotides and amino acids or organic acids present in the foods or beverages.
- 5-nucleotides may be also employed to enrich specifically the seasonings containing amino acids.
- the bitter substances in the crude preparations of 5-nucleotides can be readily removed by cation exchange resin. Both crude and purified preparations of 5-nucleotides are useful.
- alkali salts of 5-nucleotides may be also employed similarly as free 5'-nucleotides since there is no significant difference between their flavoring action.
- Example 1 50 ml. of an aqueous culture medium containing 5% of glucose, 0.5% of polypeptone, 0.05% of monobasic potassium phosphate, 0.05% of dibasic potassium phos phate, 0.04% of magnesium sulfate, and 0.04% of calcium chloride were sterilized and inoculated with a pure culture of Penicillium citrinum. After surface culture at 30 C. for five days the mycelial deck was separated from the culture broth, and washed with sterilized water. The washed mycelial deck was incubated with 50 ml. of
- the resulting reaction mixture was recognized to contain 70-80 mg. of mononucleotides, 80-90 mg. of nucleosides, and 70-80 mg. of undepolymerized polynucleotides.
- the mononucleotides, which are contained in above mixture, were identified as cytidine-- monophosphate, adenosine-S'-monophosphate, inosine-5- monop'hosphate, uridine-S'-monophosphate, and guanosine-5'-monophosphate. The identification was carried out as follows: 23 ml.
- reaction mixture were adjusted to pH 8.5 with strong sodium hydroxide solution. 2.5 ml. of 20% barium acetate solution were added thereto. The precipitate of barium phosphate formed was removed. The supernatant was adjusted to pH 5.0 with .a small quantity of acetic acid. 1 ml. of mercuric acetate solution (20% in 2% acetic acid) was added. The precipitate was centrifuged, washed and suspended in Water. Into the suspension hydrogen sulfide gas was introduced to separate nucleotides. The mixture was filtered and the precipitate was washed with hot water.
- the solution resulting from the washing was combined with the supernatant and a portion of the combined solutions was adjusted to pH 8.5, and charged into anion exchange resin DoweX-l-Cl-X-4 (200-400 mesh) column with a diameter of 1.0 cm. and 23 cm. in height, and was eluted with 0.003 N (No. l-No. 216 test tubes) and 0.010 N hydrogen chloride (No. 2l7-No. 302 test tubes).
- Each 80 drops of the eluate were collected into a test tube and optical density at 260 mg of each eluate was read. Five ultraviolet absorbing fractions A, B, C, D and E were obtained. The properties of these fractions are tabulated as follows.
- Example 2 For the formation of the strong 5'phosphodiesterase, shaking culture is more eifcctive than surface culture at least in case of the strain employed in Example 1.
- Example 1 The culture medium employed in Example 1 was inoculated with Penicillium citrinum. The inoculated growth by Albaum and Umbreit (J. Biol. Chem., 167, 369, (1047)). 3 Starting line was at 5 cm. from the end on the cathode side, and 26 cm. irom the end on the anode side.
- Example 4 Monosodium glutamate was coated with purified inosine-5-monophosphate disodium salt or guanosine-5- monophosphoric acid. The ratio of monosodium glutamate to inosine-5-monophosphate or gua-nosine-5-monophosphate was 5-5:l. The resultant superior seasoning was recognized to have remarkable flavoring properties for all kind of dishes.
- Example 5 To 120 g. of soup potage powder (corresponding to 1800 ml. of final volume) 1 to 2 g. of purified inosine- 5-monophosphate disodium salt or guanosine-5'-monophosphoric acid were added. From the result-ant enriched powder, remarkable fiavorous soup was prepared. Instead of the purified nucleotide preparations each crude preparation or mixture of 5'-nucleotides was also employed satisfactorily.
- a process for preparing 5-nucleotides which comprises growing Penicillium citrinum in an aqueous nutrient medium, recovering the 5'-phosphodiesterase from the resulting fermentation broth, incubating the recovered 5'-phosphodiesterase in an aqueous medium containing ribonucleic acid, and recovering the 5'-nucleotides from the resulting medium.
Description
United States Patent 3,223,592 PRODUCTION OF -NUCLEOTIDES Kinichiro Sakaguchi, Tokyo, and Akira Kuninaka,
Choshishi, Chihaken, Japan, assignors to Yamasa Shoyu Kabushiki Kaisha (doing business as Yamasa Shoyu Co., Ltd.), Choshi, Japan, a Japanese corporation No Drawing. Filed Aug. 22, 1958, Ser. No. 756,541
Claims priority, application Japan, Sept. 27, 1957, Bil/23,698; Apr. 28, 1958, 33/11,586 2 Claims. (Cl. 195-28) This invention relates to a process for producing the solution containing 5'-nucleotides (adenosine-5'-monophosphate, guanosine-5-monophosphate, uridine-5'-monophosphate, cytidine-5-monophosphate, inosine-5'-monophosphate, xanthosine-5'monophosphate) from ribonucleic acid by microbial 5-phosphodiesterase action, and to an application of the 5'-nucleotides as special seasonings. The object of this invention is to produce flavorous 5-nucleotides, which were so far prepared generally only by organic synthesis or by extraction from tissues of various organisms such as mammalian muscle, eco nomically and in good yield from ribonucleic acid, using the enzymes of microorganisms.
Chemical degradation of ribonucleic acid results in formation of 3- and 2-nucleotides and does not result in formation of 5-nucleotides. Furthermore general ribonucleodepolymerases, without distinction of the kind of origins, degrade ribonucleic acid into 3' (or 2')-nucleotides but not into 5'-nucleotides. Only so-called unspecific phosphodiesterases from snake venom or intestinal mucosa degrade ribonucleic acid into 5-nucleotides. However, it is very difiicult to obtain a large amount of these enzymes. 5-nucleotides can be produced by means or organic synthesis but said process is very troublesome and not economical too. Thus, hitherto, the production of 5'-nucleotides was very difficult, and especially economical mass production thereof was quite impossible.
We have found that some strains of bacteria, yeasts, and molds contain 5-phosphodiesterases which specifically hydrolyze the 5-phosphodiester linkages in ribonucleic acid and produce four 5'-nucleotides: adenosine-S-monophosphate, guanosine-S'-monophosphate, cytidine-S'-monophosphate, and uridine-5'-monophosphate. Especially the several strains which belong to the following genuses have been recognized to contain strong 5'-phosph0diesterase: Bacillus, Streptomyces, Torula, Zygosaccharomyces, Penicillium, and Aspergillus. Thus the basis of the production of 5'-nucleotides by microorganisms according to the present invention has been established for the first time.
This invention has been accomplished on the basis of the above confirmation. Therefore, the present invention provides a process for the production of 5-nucleotides which is characterized in this that ribonucleic acid is degraded into 5'-nucleotides by 5'-phosphodiesterase which is contained in living cells, dry cells, culture filtrates or cell extracts of microorganisms described above. The microorganisms containing 5-phosphodiesterase are able to be grown on either solid media or liquid media. For economical mass production, however, liquid media are more appropriate. As the components of the culture medium, the conventional carbon and nitrogen sources and several inorganic salts may be employed effectively. This invention includes both one step method and two step method. In one step method, both growing of microorganism and enzymic degradation of ribonucleic acid are carried out simultaneously, em-
Patented Dec. 14, 1965 ploying culture medium containing ribonucleic acid. In two step method, growing of microorganism and enzymic degradation of ribonucleic acid are carried out separately.
According to the present invention, it is not necessary to purify ribonucleic acid before its enzymic degradation. Crude solution containing ribonucleic acid, such as yeast extracts, may be used as an appropriate starting material. Furthermore microbial cells cultivated for producing 5- phosphodiesterase are effectively utilized too as a source of ribonucleic acid.
Free 5'-nucleotides or their alkali salts obtained by the processing as described above enhance or increase the flavor of the foods, beverages, and seasonings in which they are placed. This flavoring action is caused by the synergy between 5-nucleotides and amino acids or organic acids. According to our discovery purine and pyrimidine bases, their nucleosides, and their 2'- and 3-nucleotides have little flavor, while 5'-nucleotides, especially inosine-S'-monophosphate, guanosine-5-monophosphate, and xanthosine-S'-monophosphate, have very agreeable good taste. Furthermore, there is specific synergy in taste between 5-nucleotides and amino acids or organic acids. Among various amino acids, glutamic and aspartic acids were recognized to be especially effecctive in the synergy with 5-nucleotides. General foods, beverages, and seasonings contain considerable quantity of amino acids or organic acids as main flavoring components, but scarcely contain 5-nucleotides. Therefore, it seems that the role of S'-nucleotides in flavoring is very important. For example the good taste of soups or meat extracts, containing small quantity of 5'-nucleotides, may be perhaps caused mainly by the synergy between 5'-nucleotides and amino acids.
This invention relates also to the application of 5'- nucleotides based on the utilization of aforesaid synergy between 5-nucleotides and amino acids or organic acids. The application of 5 -nucleotides according to the present invention comprises adding one or more of 5-nucleotides to general foods or beverages such as meat products, soups, roux, vinegar, various dressings, sauces, curry powder and various drinks including wine, to counteract the displeasing pungency which spoils the taste qualities of foods or beverages, and to enhance or increase the flavor specifically according to the synergy between 5-nucleotides and amino acids or organic acids present in the foods or beverages. In case of application for the foods or beverages containing no amino acids, it is more effective to add monosodium glutamic acid and 5'-nucleotides together. 5-nucleotides may be also employed to enrich specifically the seasonings containing amino acids. The bitter substances in the crude preparations of 5-nucleotides can be readily removed by cation exchange resin. Both crude and purified preparations of 5-nucleotides are useful.
According to the present invention, alkali salts of 5-nucleotides may be also employed similarly as free 5'-nucleotides since there is no significant difference between their flavoring action.
The invention is illustrated but not limited by the following examples.
Example 1 50 ml. of an aqueous culture medium containing 5% of glucose, 0.5% of polypeptone, 0.05% of monobasic potassium phosphate, 0.05% of dibasic potassium phos phate, 0.04% of magnesium sulfate, and 0.04% of calcium chloride were sterilized and inoculated with a pure culture of Penicillium citrinum. After surface culture at 30 C. for five days the mycelial deck was separated from the culture broth, and washed with sterilized water. The washed mycelial deck was incubated with 50 ml. of
0.5% yeast ribonucleic acid solution containing 0.01 N sodium fluoride at 30 C. After 22.5 hours the deck was removed. The resulting reaction mixture was recognized to contain 70-80 mg. of mononucleotides, 80-90 mg. of nucleosides, and 70-80 mg. of undepolymerized polynucleotides. The mononucleotides, which are contained in above mixture, were identified as cytidine-- monophosphate, adenosine-S'-monophosphate, inosine-5- monop'hosphate, uridine-S'-monophosphate, and guanosine-5'-monophosphate. The identification was carried out as follows: 23 ml. of the reaction mixture were adjusted to pH 8.5 with strong sodium hydroxide solution. 2.5 ml. of 20% barium acetate solution were added thereto. The precipitate of barium phosphate formed was removed. The supernatant was adjusted to pH 5.0 with .a small quantity of acetic acid. 1 ml. of mercuric acetate solution (20% in 2% acetic acid) was added. The precipitate was centrifuged, washed and suspended in Water. Into the suspension hydrogen sulfide gas was introduced to separate nucleotides. The mixture was filtered and the precipitate was washed with hot water. The solution resulting from the washing was combined with the supernatant and a portion of the combined solutions was adjusted to pH 8.5, and charged into anion exchange resin DoweX-l-Cl-X-4 (200-400 mesh) column with a diameter of 1.0 cm. and 23 cm. in height, and was eluted with 0.003 N (No. l-No. 216 test tubes) and 0.010 N hydrogen chloride (No. 2l7-No. 302 test tubes). Each 80 drops of the eluate were collected into a test tube and optical density at 260 mg of each eluate was read. Five ultraviolet absorbing fractions A, B, C, D and E were obtained. The properties of these fractions are tabulated as follows.
medium was shaken on a reciprocating shaker at C. After 7 days culture filtrates were concentrated in vacuo, and then dialyzed against running water over night. To the dialyzed solution 4 volumes of ethanol were added. The resulting precipitate, which was rich in 5'phosphodiesterase activity, was dried up in a desiccator and was employed as an enzyme preparation. From 1 litre of culture filtrates about 1 g. of the preparation was obtained. 1 g. of this preparation was incubated with 200 ml. of 5% ribonucleic acid at C. and pH 5.0. Under these conditions phosphomonoeste-rase and adenyl deaminase were almost inactive, while 5'phosphodiestera-se was recognized to be very active.
The reaction proceeds as described below.
Incubation time (min) 0 I 10 30 i 60 5'nucleotides formation from ribonucleic acid (percent) 27 68 96 97 Inorg. P. formation from 5'nucleotides (percent) 3.0 3. 5 4. 5 5. 7
Example 3 100-500 mg. of the crude mixture of adeno=sine-5'- Nucleotide traction obtained Standard substance Fraction A B C D E Cytidine- Adenosine- Adenosine- Inosine- Urldine- Guanosine- Mixture 3-mono- 3-mono- 5'mono- 5'mono- 3-mono- 3-monooi 3- nuphosphate phosphate phosphate phosphate phosphate phosphate cleotldcs No of test tube 21-24 43-54 121-122 221-237 264-281 Rm (Inn) 1 275 258 249 262 257 278 257 257 250 262 257 258 Percent color development. pentoseorcinoi reaction:
7 min 78. 7 82.2 81. 6 80. 4 39.6 97. 2 95. 7 72. 8 100. 0 100. 0 94. 7 96.3 95.4 99. 0 92. 8 92. 1 100. 0 arbazole reaction. blue purple. blueblue purple. Distance 3 migrated from origin to anode side by electrophoresis (0111.) 4. 9 4. 9 12. 5 14. 7 7. 7 4. 9 5. 0 4. 5 12.5 15.0 8. 8 14.8,8.7,4.7 NalOi-rosaniline reaction I Ultraviolet absorption spectra 01 standard substances were measured in 0.1 N H01.
2 The technique employed was essentially the same as that described The results shown in the table indicate that the ultraviolet absorbing substances which are contained in fractions A, B, C, D and E are cytidine-S-monophosphate, adenOsine-S -monophosphate, inosine-S '-monopho-sphate, uridine-S-monophosphate, and guanosine-5'-mor1ophosp'hate, respectively. It seems very probable that inosine- 5'monophosphate recognized in this example was produced secondarily from adenosine-S-monophosphate by the action of Henicillium deaminase. In this example the formation of xarithosine-S-monophosphate was not recognized. However, this compound was easily obtained enzymatically or chemically from guanosinc-5'-monophophate.
Example 2 For the formation of the strong 5'phosphodiesterase, shaking culture is more eifcctive than surface culture at least in case of the strain employed in Example 1.
The culture medium employed in Example 1 Was inoculated with Penicillium citrinum. The inoculated growth by Albaum and Umbreit (J. Biol. Chem., 167, 369, (1047)). 3 Starting line was at 5 cm. from the end on the cathode side, and 26 cm. irom the end on the anode side.
Example 4 Monosodium glutamate was coated with purified inosine-5-monophosphate disodium salt or guanosine-5- monophosphoric acid. The ratio of monosodium glutamate to inosine-5-monophosphate or gua-nosine-5-monophosphate was 5-5:l. The resultant superior seasoning was recognized to have remarkable flavoring properties for all kind of dishes.
Example 5 To 120 g. of soup potage powder (corresponding to 1800 ml. of final volume) 1 to 2 g. of purified inosine- 5-monophosphate disodium salt or guanosine-5'-monophosphoric acid were added. From the result-ant enriched powder, remarkable fiavorous soup was prepared. Instead of the purified nucleotide preparations each crude preparation or mixture of 5'-nucleotides was also employed satisfactorily.
In case of soup consum-m being prepared inosine-5'- monophosphate, guanosine-S-monophosphate, and mixture of 5'-nuoleotides were employed effectively too.
What we claim is:
1. A process for preparing 5'-nucleotides which compnises intimately contacting ribonucleic acid in an aqueous medium with a 5-phosphodiesterase=containing enzyme produced by Penicillium citrinum, and recovering the 5'- nucleotides from the resulting medium.
2. A process for preparing 5-nucleotides which comprises growing Penicillium citrinum in an aqueous nutrient medium, recovering the 5'-phosphodiesterase from the resulting fermentation broth, incubating the recovered 5'-phosphodiesterase in an aqueous medium containing ribonucleic acid, and recovering the 5'-nucleotides from the resulting medium.
References Cited by the Examiner UNITED STATES PATENTS OTHER REFERENCES Cohn et al.: Journal of Biological Chemistry, vol. 203, July-August 1953, pages 319 to 331.
Dixon et al.: Enzymes, published by Academic Press Inc., New York, 1958, pages 190, 191 and 690.
A. LOUIS MONACELL, Primary Examiner.
ABRAHAM WINKELSTEIN, TOBIAS E. LEVOW,
Examiners.
Claims (1)
1. A PROCESS FOR PREPARING 5''-NUCLEOTIDES WHICH COMPRISES INTIMATELY CONTACTING RIBONUCLEIC ACID IN AN AQUEOUS MEDIUM WITH A 5''-PHOSPHODIESTERASE-CONTAINING ENZYME PRODUCED BY PENICILLIUM CITRINUM, AND RECOVERING THE 5''NUCLEOTIDES FROM THE RESULTING MEDIUM.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US158108A US3104171A (en) | 1958-08-22 | 1961-12-08 | Process for improving the flavor of foods by the addition of 5'-nucleotides |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2369857 | 1957-09-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3223592A true US3223592A (en) | 1965-12-14 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US756541A Expired - Lifetime US3223592A (en) | 1957-09-27 | 1958-08-22 | Production of 5'-nucleotides |
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| US (1) | US3223592A (en) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3397700A (en) * | 1966-05-16 | 1968-08-20 | American Tobacco Co | Flavor enhanced cigarettes and cigars |
| US3410754A (en) * | 1965-09-17 | 1968-11-12 | Takeda Chemical Industries Ltd | Production of 5'-nucleotides |
| US5708157A (en) * | 1996-07-26 | 1998-01-13 | Genetics Institute, Inc. | Secreted proteins and polynucleotides encoding them |
| US5831056A (en) * | 1996-06-07 | 1998-11-03 | Genetics Institute, Inc. | Secreted proteins and polynucleotides encoding them |
| US20090297662A1 (en) * | 2006-12-04 | 2009-12-03 | Ajinomoto Co., Inc | Process for producing seasoning |
| WO2016160936A1 (en) | 2015-03-30 | 2016-10-06 | Greenlight Biosciences, Inc. | Cell-free production of ribonucleic acid |
| US9611487B2 (en) | 2012-12-21 | 2017-04-04 | Greenlight Biosciences, Inc. | Cell-free system for converting methane into fuel and chemical compounds |
| US9688977B2 (en) | 2013-08-05 | 2017-06-27 | Greenlight Biosciences, Inc. | Engineered phosphoglucose isomerase proteins with a protease cleavage site |
| US10006062B2 (en) | 2010-05-07 | 2018-06-26 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for control of flux in metabolic pathways through enzyme relocation |
| US10036001B2 (en) | 2010-08-31 | 2018-07-31 | The Board Of Trustees Of The Leland Stanford Junior University | Recombinant cellular iysate system for producing a product of interest |
| US10858385B2 (en) | 2017-10-11 | 2020-12-08 | Greenlight Biosciences, Inc. | Methods and compositions for nucleoside triphosphate and ribonucleic acid production |
| US10954541B2 (en) | 2016-04-06 | 2021-03-23 | Greenlight Biosciences, Inc. | Cell-free production of ribonucleic acid |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1680865A (en) * | 1925-08-07 | 1928-08-14 | Fujii Masao | Method of neutralizing acidity or alkalinity of decomposed product or products by glutamic acid or its salts |
| US2174475A (en) * | 1937-10-13 | 1939-09-26 | Georg Henning Chem Pharm Werk | Enzymatic manufacture of nucleotides |
| US2342760A (en) * | 1939-08-04 | 1944-02-29 | Schwaneberg Herbert | Process for the manufacture of alkaline earth metal salts of adenosine polyphosphoric acids |
| US2512385A (en) * | 1949-08-31 | 1950-06-20 | Arlington Chemical Company | Flavor developing composition |
| US2844514A (en) * | 1953-11-04 | 1958-07-22 | Pabst Brewing Co | Process for the production of nucleotides |
| US3104171A (en) * | 1958-08-22 | 1963-09-17 | Yamasa Shoyu Kk | Process for improving the flavor of foods by the addition of 5'-nucleotides |
-
1958
- 1958-08-22 US US756541A patent/US3223592A/en not_active Expired - Lifetime
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1680865A (en) * | 1925-08-07 | 1928-08-14 | Fujii Masao | Method of neutralizing acidity or alkalinity of decomposed product or products by glutamic acid or its salts |
| US2174475A (en) * | 1937-10-13 | 1939-09-26 | Georg Henning Chem Pharm Werk | Enzymatic manufacture of nucleotides |
| US2342760A (en) * | 1939-08-04 | 1944-02-29 | Schwaneberg Herbert | Process for the manufacture of alkaline earth metal salts of adenosine polyphosphoric acids |
| US2512385A (en) * | 1949-08-31 | 1950-06-20 | Arlington Chemical Company | Flavor developing composition |
| US2844514A (en) * | 1953-11-04 | 1958-07-22 | Pabst Brewing Co | Process for the production of nucleotides |
| US3104171A (en) * | 1958-08-22 | 1963-09-17 | Yamasa Shoyu Kk | Process for improving the flavor of foods by the addition of 5'-nucleotides |
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| US3410754A (en) * | 1965-09-17 | 1968-11-12 | Takeda Chemical Industries Ltd | Production of 5'-nucleotides |
| US3397700A (en) * | 1966-05-16 | 1968-08-20 | American Tobacco Co | Flavor enhanced cigarettes and cigars |
| US5831056A (en) * | 1996-06-07 | 1998-11-03 | Genetics Institute, Inc. | Secreted proteins and polynucleotides encoding them |
| US5708157A (en) * | 1996-07-26 | 1998-01-13 | Genetics Institute, Inc. | Secreted proteins and polynucleotides encoding them |
| US5786465A (en) * | 1996-07-26 | 1998-07-28 | Genetics Institute, Inc. | Secreted proteins and polynucleotides encoding them |
| US20090297662A1 (en) * | 2006-12-04 | 2009-12-03 | Ajinomoto Co., Inc | Process for producing seasoning |
| US10006062B2 (en) | 2010-05-07 | 2018-06-26 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for control of flux in metabolic pathways through enzyme relocation |
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| US9611487B2 (en) | 2012-12-21 | 2017-04-04 | Greenlight Biosciences, Inc. | Cell-free system for converting methane into fuel and chemical compounds |
| US9688977B2 (en) | 2013-08-05 | 2017-06-27 | Greenlight Biosciences, Inc. | Engineered phosphoglucose isomerase proteins with a protease cleavage site |
| US10421953B2 (en) | 2013-08-05 | 2019-09-24 | Greenlight Biosciences, Inc. | Engineered proteins with a protease cleavage site |
| WO2016160936A1 (en) | 2015-03-30 | 2016-10-06 | Greenlight Biosciences, Inc. | Cell-free production of ribonucleic acid |
| EP3277808A4 (en) * | 2015-03-30 | 2019-05-22 | Greenlight Biosciences, Inc. | Cell-free production of ribonucleic acid |
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| US10858385B2 (en) | 2017-10-11 | 2020-12-08 | Greenlight Biosciences, Inc. | Methods and compositions for nucleoside triphosphate and ribonucleic acid production |
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