WO2017200050A1 - Extrait de levure riche en β－ｎｍｎ - Google Patents

Extrait de levure riche en β－ｎｍｎ Download PDF

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WO2017200050A1
WO2017200050A1 PCT/JP2017/018709 JP2017018709W WO2017200050A1 WO 2017200050 A1 WO2017200050 A1 WO 2017200050A1 JP 2017018709 W JP2017018709 W JP 2017018709W WO 2017200050 A1 WO2017200050 A1 WO 2017200050A1
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nmn
yeast
yeast extract
enzyme
reaction
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PCT/JP2017/018709
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English (en)
Japanese (ja)
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祐一郎 深水
一成 田崎
亮治 立山
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興人ライフサイエンス株式会社
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Priority to JP2018518359A priority Critical patent/JP6997080B2/ja
Publication of WO2017200050A1 publication Critical patent/WO2017200050A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L31/00—Edible extracts or preparations of fungi; Preparation or treatment thereof
    • A23L31/10—Yeasts or derivatives thereof
    • A23L31/15—Extracts
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • 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
    • C12P1/00—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes
    • C12P1/02—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes by using fungi
    • 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

Definitions

  • the present invention relates to a molecule that activates a food standard longevity gene (sirtuin), which comprises a step of allowing a crude enzyme prepared from Rhizopus genus such as Rhizopus oryzae to act on an extract obtained by culturing Candida utilis (provided is a method for producing a yeast extract containing a high content of “ ⁇ -Nicotinamide mononucleotide ( ⁇ -NMN)”, a sirtuin activator).
  • ⁇ -N ⁇ -Nicotinamide mononucleotide
  • ⁇ -Nicotinamide mononucleotide is an intermediate metabolite of ⁇ -Nicotinamide adenine dinucleotide (NAD), which is a metabolite of the de novo pathway and the Salvage pathway in vivo (Patent Documents 1 to 4, Non-Patent Document 1) ).
  • NAD ⁇ -Nicotinamide adenine dinucleotide
  • ⁇ -NMN can directly induce biosynthesis of NAD and improve the NAD concentration in tissues when administered to a living body (Non-patent Document 2).
  • Non-patent Document 2 the presence of SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, and SIRT7 protein families has been confirmed in humans as proteins encoded by sirtuin genes (Non-patent Document 1).
  • Non-patent Document 1 functions related to ⁇ -NMN, which is a sirtuin activator, include “improvement of abnormal sugar metabolism (Non-patent Document 2)”, “participation in Circadian rhythm (Non-patent Document 3) 4” ) '', ⁇ Functional improvement of aging mitochondria (Non-patent document 5) '', ⁇ Protection of heart from ischemia-reperfusion (Non-patent document 6) '', ⁇ Inhibition of neural stem cell decrease due to aging (Non-patent document 7) '' ”,“ Epigenetic control mechanism suppresses claudin-1 expression and diminishes albuminuria in diabetic nephropathy (Non-patent document 8) ”,“ Control of programmed cell death (Non-patent document 9)
  • Torula yeast (Candida utilis) is an edible yeast that has been evaluated for higher nutritional functionality and safety from eating experience than the US Food and Drug Administration (FAD). For this reason, it has been used effectively for many years in medicines, supplements and seasonings.
  • ⁇ -NMN is sold only for research purposes, and no food-standard products are sold. Therefore, it is an object to obtain a yeast extract containing ⁇ -NMN from yeast with experience of eating, and to obtain a composition with a high content of ⁇ -NMN derived from yeast.
  • the present inventor extracted yeast extract from yeast and optimized (temperature 45 to 60 ° C., pH 4.5 to 6.0) with an enzyme or a crude enzyme obtained from a microorganism belonging to the genus Rhizopus such as Rhizopus oryzae. It has been found that a yeast extract enriched with ⁇ -NMN can be obtained by carrying out an enzymatic reaction, and the present invention has been completed.
  • the invention is as follows.
  • B Optimum pH: pH 4.5 to 6.0.
  • Origin A microorganism belonging to the genus Rhizopus.
  • ⁇ -Nicotinamide mononucleotide can be easily obtained from yeast with experience in food.
  • Torula yeast is a yeast that has been eating for a long time, and the yeast extract obtained from this is highly safe.
  • Such yeast extract containing a high content of ⁇ -Nicotinamide mononucleotide can be ingested as pharmaceuticals, supplements, functional foods and the like.
  • the calibration curve used for the determination of ⁇ -NMN and NAD in the yeast extract obtained by the reaction of the extract prepared from Candida utilis IAM 4264 and the crude enzyme derived from Rhizopus oryzae is shown.
  • Results of Example 7. It is a chromatogram showing ⁇ -NMN and NAD in a yeast extract obtained by the reaction of an extract prepared from Candida utilis IAM 4264 and a crude enzyme derived from Rhizopus oryzae.
  • Results of Example 7. 3 is a graph showing ⁇ -NMN and NAD contents in a yeast extract obtained by the reaction of an extract prepared from Candida utilis IAM 4264 ⁇ and a crude enzyme derived from Rhizopus oryzae. This reaction mechanism of ⁇ -NMN production by adding an extract prepared from Candida utilis IAM 4264 and a crude enzyme derived from Rhizopus oryzae is shown.
  • edible yeast can be used as yeast.
  • yeast belonging to the genus Saccharomyces, Kluyveromyces genus, Candida genus, Pichia genus and the like can be mentioned, among which Candida genus Candida utilis is preferable.
  • Candidaandutilis IAM 4264, Candida utilis ATCC 9950, Candida utilis ATCC 9550, Candida utilis IAM 4233, Candida utilis AHU 3259 and the like More preferably, the use of yeast with a high glutathione content increases the ⁇ -NMN content.
  • yeast having a high glutathione content yeasts obtained by known methods can be used (Japanese Patent Laid-Open Nos. 59-151894, 60-156379, etc.).
  • glucose, acetic acid, ethanol, glycerol, molasses, sulfite pulp waste liquid, etc. are used as carbon sources, and nitrogen, urea, ammonia, ammonium sulfate, ammonium chloride, Nitrate is used.
  • Phosphoric acid, potassium, and magnesium sources may be ordinary industrial raw materials such as lime perphosphate, ammonium phosphate, potassium chloride, potassium hydroxide, magnesium sulfate, magnesium chloride, and other zinc, copper, manganese, iron ions, etc.
  • Add inorganic salt Others can be cultured without using vitamins, amino acids, nucleic acid-related substances, etc., but these may be added.
  • Organic substances such as cone-briker, casein, yeast extract, meat extract and peptone may be added.
  • Culture conditions such as culture temperature and pH can be applied without particular limitation, and may be set according to the yeast strain used and cultured.
  • the culture temperature is 21 to 37 ° C., preferably 25 to 34 ° C.
  • the pH is 3.0 to 8.0, particularly 3.5 to 7.0.
  • the culture format of the present invention may be either batch culture or continuous culture, but the latter is desirable industrially. Conditions such as agitation and aeration during culture are not particularly limited and may be a general method.
  • an extract is prepared by pretreatment. Extraction is performed after washing the wet yeast cells after culturing the cells by suspending them in distilled water and repeating centrifugation.
  • the extraction method may be appropriately adjusted according to the type of yeast used, but in order to increase the content of ⁇ -NMN, NAD (nicotinamide adenine dinucleotide nucleotide), ⁇ - It is desirable to carry out under the condition that NMN is not decomposed.
  • the self-digestion method, the alkali extraction method, the hot water extraction method, or a combination thereof is used.
  • the suspension is resuspended in distilled water so that the bacterial cell concentration is 7 to 10%, preferably 8 to 9%, in terms of dry weight.
  • pH adjustment is performed as necessary. Most preferably, the pH during extraction is adjusted to around 6.0. The pH may be adjusted by a known method.
  • Extraction temperature is 50 to 90 ° C, preferably 50 to 65 ° C.
  • a known method can be used without particular limitation as long as the extract reaches the above temperature.
  • Extraction time may be 5 minutes or more. It is desirable to stir during extraction. The stirring speed and the like may be adjusted as appropriate and are not particularly limited. Further, when the extraction time is 40 to 50 minutes, the content of ⁇ -NMN increases, which is more preferable.
  • the cell suspension After extraction, the cell suspension is removed by centrifugation to obtain a supernatant. This supernatant was used as an extract and a substrate solution for the enzyme reaction according to the present invention.
  • the enzyme used is an enzyme that produces ⁇ -NMN using NAD contained in the solution obtained up to the previous stage as a substrate.
  • an enzyme derived from a filamentous fungus belonging to the genus Rhizopus is used.
  • the Rhizopus genus include Rhizopus oryzae, Risopus microsporus, Rhizopus oligosporus, etc., and an enzyme derived from the genus zoRhizopus genus with experience in eating can be used.
  • a crude enzyme prepared from a microorganism belonging to the genus Rhizopus as described above can be used.
  • the microorganism belonging to the genus Rhizopus may be a strain used in the food industry.
  • Rhizopus genus fungi such as Rhizopus oryzae are particularly preferred because they are used in the production of enzyme production such as protease (JP 2010-004760 A, etc.).
  • the filamentous fungus belonging to the genus Rhizopus may be a strain obtained from strain distribution agencies such as ATCC, NBRC, or a commercially available seed strain sales company.
  • a crude enzyme used in the present invention can be prepared by a general enzyme preparation method.
  • a fraction containing a protein group such as an enzyme is obtained through a cell culture and a crude purification step by chromatography. Since a crude enzyme can be used in the present application, a fraction containing a protein group from a culture solution, or a fraction containing an intracellular protein group by crushing the culture solution and Rhizopus oryzae may be used. It is good also as a dried material by obtaining a drying process. Furthermore, various enzymes derived from the genus Rhizopus are commercially available, and since many of these commercially available enzymes contain contaminating enzymes, enzymes that can be used in the method of the present application are also available.
  • the above enzymes are enzymes that produce NMN using NAD as a substrate, and can be used not only for NAD in yeast, but also for enzymes that produce NMN using NAD pure products as substrates. NAD can use what is generally available.
  • the amount of the enzyme used for the reaction varies depending on the method for preparing the enzyme, but is usually 0.05% (w / v) to 0.25% (w / v), preferably 0.1% (w / V) Add.
  • the ⁇ -NMN measurement method used for studying the optimal reaction conditions for the enzyme depends on the LC-MS measurement conditions described in the Examples.
  • the optimum temperature for the reaction of the crude enzyme is 45 to 60 ° C, preferably 50 to 55 ° C, and most preferably 55 ° C.
  • the detection method of ⁇ -NMN used for the examination of the optimum reaction conditions of the enzyme in the present application is based on the LC-MS measurement conditions described in the Examples.
  • the optimum pH for the reaction of the crude enzyme is 4.5 to 6.0, preferably 5.0 to 5.5, most preferably pH 5.0.
  • the detection method of ⁇ -NMN used for the examination of the optimum reaction conditions of the enzyme in the present application is based on the LC-MS measurement conditions described in the Examples.
  • a yeast extract containing the above ⁇ -NMN can be obtained.
  • the ⁇ -NMN of the present invention differs in the content of ⁇ -NMN produced by the NAD content in yeast. Increasing the NAD content contained in the substrate solution of the enzyme reaction extracted from the yeast cells can further increase ⁇ -NMN.
  • the detection method of ⁇ -NMN used for the examination of the optimum reaction conditions of the enzyme in the present application is based on the LC-MS measurement conditions described in the Examples.
  • the extract subjected to the enzyme reaction can be concentrated and then freeze-dried or hot-air dried to obtain a dried product of ⁇ -NMN-containing yeast extract. Further, by purifying ⁇ -NMN from the ⁇ -NMN-containing yeast extract, it is possible to obtain a composition further enriched in yeast-derived ⁇ -NMN. In addition, a composition enriched in yeast-derived ⁇ -NMN can also be obtained by purifying ⁇ -NMN from the yeast extract before drying in the previous stage. As a purification method, a general purification method using an ion exchange resin or the like can be used.
  • the method of ingesting the yeast extract or yeast-derived ⁇ -NMN-containing composition of the present invention is not particularly limited, and examples include oral administration, parenteral administration such as intravenous, intraperitoneal or subcutaneous administration.
  • parenteral administration such as intravenous, intraperitoneal or subcutaneous administration.
  • oral preparations such as tablets, powders, granules, pills, suspensions, emulsions, soaking and decoction, capsules, syrups, solutions, elixirs, extracts, tinctures, fluid extracts, Or any of parenterals such as injections, drops, creams, suppositories, etc. may be used.
  • the yeast yeast extract can be ingested not only as a medicine but also as a food, and can also be ingested as a functional food, a nutritional supplement, a supplement and the like.
  • the present invention can also be used in combination with other compositions that do not decrease the sirtuin activity of ⁇ -NMN or enhance the sirtuin activity of ⁇ -NMN.
  • excipients for example, excipients, diluents, dextrins, malt tols, sorbitol, starch and the like.
  • the amount of intake according to the present invention may be administered in such an amount that the sirtuin activity of ⁇ -NMN is expressed.
  • the dose required for ⁇ -NMN activity is determined by the condition of the consumer, the choice of composition administered, the age, weight and response of the consumer, the condition of the consumer, etc. Is done.
  • Wakosil-II 5C18 RS particle size 5 um, length 30 mm, inner diameter 4.6 mm
  • Wakosil-II 5C18 RS particle diameter 5 um, length 150 mm, inner diameter 4.6 mm
  • Wakosil-II 5C18 RS particle diameter 5 um, length 250 mm, inner diameter 4.6 mm
  • Candida utilis IAM 4264 is pre-cultured in an Erlenmeyer flask containing YPD medium (yeast extract 1%, polypeptone 2%, glucose 2%) in advance, and this is 1-2% in 18 L medium in a 30 L fermentor. Inoculated. Medium composition is 4% glucose, 0.3% monoammonium phosphate, 0.161% ammonium sulfate, 0.137% potassium chloride, 0.08% magnesium sulfate, 1.6 ppm copper sulfate, 14 ppm iron sulfate, Manganese sulfate 16 ppm and zinc sulfate 14 ppm were used.
  • the culture conditions were pH 4.0, culture temperature 30 ° C., aeration rate 1 vvm, stirring 600 rpm, and ammonia was added to control the pH. After culturing the cells for 16 hours, the culture solution was collected and collected by centrifugation to obtain 180 g of wet yeast cells. The obtained yeast cells were washed by suspending them in distilled water and repeating the centrifugation. Resuspended in distilled water to a dry solids concentration of 82.88 g / L. At this time, the pH was 5.8.
  • Example 1 (Yeast extract extraction) The cell suspension is heated to 90 ° C. while gently stirring the suspension in a water bath at 95 ° C. and subjected to extraction for 10 minutes while stirring. After the extraction treatment, 25 mL of the sampled cell suspension was cooled under ice and centrifuged at 10,000 rpm for 10 minutes at 4 ° C. to obtain a supernatant. The same amount of ultrapure water as the supernatant was added to the precipitate, suspended, and centrifuged again to obtain the supernatant. The supernatant obtained by the first centrifugation and the supernatant obtained by the second centrifugation were pooled, and the extract was filled up to 50 mL with ultrapure water.
  • Example 2 Mass spectrum of ⁇ -NMN and NAD standard
  • mass spectra of ⁇ -NMN and NAD were obtained.
  • FIG. 2 when ⁇ / NMN was subjected to MS / MS using ⁇ / NMN m / z 334 as a precursor ion, a fragment ion of Nicotinamide (Nam) m / z 123 was detected.
  • this precursor ion m / z 335 and fragment ion m / z 123 were subjected to LC-MS / MS under the above-mentioned conditions, ⁇ -NMN was detected at 3.0 min as shown in FIG. As shown in FIG.
  • NAD is obtained by performing MS / MS using NAD m / z 664 as a precursor ion, m / z 524 and m / z 542 derived from Adenosine diphosphate ribose (ADP-ridose), Adenosine Diphosphate (ADP) m / z 428 and Ribose 5-phosphate (R5P) m / z 232 fragment ions were detected.
  • ADP-ridose Adenosine diphosphate ribose
  • ADP Adenosine Diphosphate
  • R5P Ribose 5-phosphate
  • Example 3 (Examination of optimal enzyme reaction temperature) Yeast was cultured and extracted in the same manner as in Example 1, and the temperature of the yeast extract was 30 ° C, 35 ° C, 40 ° C, 45 ° C, 50 ° C, 52 ° C, 53 ° C, 54 ° C, 55 ° C, 56 ° C, respectively. , 58 ° C., 60 ° C., 62 ° C., 65 ° C., 70 ° C., the reaction pH was adjusted to 6.5 with 9 N HCl or 9 N NaOH, and 0.1% (w / v) of the crude enzyme prepared from Rhizopus oryzae ) After the addition amount, the enzyme reaction was carried out for 1 hour.
  • the production rate of ⁇ -NMN at each temperature as measured by LC-MS was as shown in FIG.
  • the highest ⁇ -NMN production rate was exhibited when the reaction temperature was 45-60 ° C, particularly around 55 ° C.
  • the ⁇ -NMN production rate indicates a relative value when the ionic strength of ⁇ -NMN in the extract not reacted with the enzyme is 1.
  • the ionic strength was measured by LC-MS.
  • Example 4 (Examination of optimum enzyme reaction pH) Yeast was cultured and extracted in the same manner as in Example 1, the temperature of the yeast extract was 54 ° C., the reaction pH was 9 N HCl or 9 N NaOH, pH 4.0, pH 4.5, pH 5.0, pH 5.5, The pH was adjusted to 6.0, pH 6.5, pH 7.0, and pH 7.5, and 0.1% (w / v) of the crude enzyme prepared from Rhizopus oryzae was added, and the enzyme reaction was performed for 1 hour. The production rate of ⁇ -NMN at each pH as measured by LC-MS was as shown in FIG.
  • the highest ⁇ -NMN production rate was exhibited when the reaction pH was in the range of 4.5 to 6.0, particularly around pH 5.0.
  • the ⁇ -NMN production rate indicates a relative value when the ionic strength of ⁇ -NMN in the extract not reacted with the enzyme is 1.
  • the ionic strength was measured by LC-MS.
  • Example 5 (Examination of metal ion requirement of enzyme) Yeast was cultured and extracted in the same manner as in Example 1, the temperature of the yeast extract was adjusted to 55 ° C., the reaction pH was adjusted to pH 5.0 with 9 N HCl or 9 N NaOH, and the final concentration was 100 mM.
  • the presence of Zn ions, Cu ions, and Fe ions in the reaction solution was shown to inhibit the formation of ⁇ -NMN. Furthermore, since EDTA, which is a chelating agent, is present in the reaction solution, it exhibits ⁇ -NMN-forming activity, so that the addition of a metal compound is not necessary for this enzyme reaction.
  • the production rate of ⁇ -NMN is a relative value when the ionic strength of ⁇ -NMN in the solution after the enzyme reaction without addition of a metal compound is taken as 100. The ionic strength was measured by LC-MS.
  • Example 6 (Examination of optimal enzyme addition amount and enzyme reaction time) Yeast was cultured and extracted in the same manner as in Example 1, the temperature of the yeast extract was adjusted to 55 ° C., the reaction pH was adjusted to pH 5.0 with 9 N HCl or 9 N NaOH, and the crude enzyme prepared from Rhizopus oryzae was adjusted to 0. .010% (w / v), 0.025% (w / v), 0.050% (w / v), 0.10% (w / v), 0.25% (w / v), 0 Enzymatic reaction was carried out for 5 hours after addition of 50% (w / v), 0.75% (w / v) and 1.0% (w / v) respectively.
  • the highest ⁇ -NMN production rate was the enzyme reaction for 3 hours with the addition of 0.10% (w / v).
  • the ⁇ -NMN production rate indicates a relative value when the ionic strength of ⁇ -NMN in the extract not reacted with the enzyme is 1.
  • the ionic strength was measured by LC-MS.
  • Example 7 (Measurement of ⁇ -NMN content under optimal enzyme reaction conditions) Using Candida utilis IAM 4264, yeast was cultured and extracted in the same manner as in Example 1, the temperature of the yeast extract was adjusted to 55 ° C., the reaction pH was adjusted to pH 5.0 with 9 N HCl or 9 N NaOH, and Rhizopus After adding 0.1% (w / v) of crude enzyme prepared from oryzae, an optimal reaction was performed for 3 hours. Thereafter, a dried yeast extract containing ⁇ -NMN was obtained by a drying step. The dried product was quantitatively analyzed under the above measurement conditions. The chromatogram is as shown in FIG.
  • the ⁇ -NMN content in the yeast extract under the optimal enzyme reaction conditions was determined by quantifying ⁇ -NMN using the calibration curve crude of FIG. 8, and as shown in FIG. w). Before the reaction, NAD was contained at 2.29% (w / w) per dry solid content, and after the reaction, NAD decreased to 0.18% (w / w) per dry solid content, and ⁇ -NMN Has been generated. From this, the mechanism as shown in FIG. 11 is predicted for the production of ⁇ -NMN by this enzyme reaction.
  • Example 8 Production of ⁇ -NMN was confirmed using a commercially available enzyme belonging to the genus Rhizopus.
  • a yeast extract was prepared, and 0.1% (w / v) of commercially available enzyme “Lipase A-10D” (manufactured by Nagase ChemteX) was added for 3 hours for optimal reaction. went.
  • the reaction conditions were pH 5.0 and temperature 55 ° C.
  • a yeast extract containing 2.01% (w / w) of ⁇ -NMN could be obtained.
  • ⁇ -NMN can be obtained from edible safe yeast and can be ingested not only as a pharmaceutical product, but also as a functional food and a dietary supplement. By ingesting the product of the present invention, the functionality possessed by ⁇ -NMN is obtained. I can do it.

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Abstract

L'invention a pour objet de fournir un extrait de levure comprenant un β－ＮＭＮ à partir d'une levure reconnue en tant qu'aliment, et de fournir une composition de β－ＮＭＮ dérivée d'une levure. Plus précisément, l'extrait de levure qui comprend 2,0%(w/w) ou plus de β－ＮＭＮ pour sa matière sèche, est obtenu par réaction au moyen d'une enzyme brute préparée à partir de microorganismes appartenant aux Rhizopus tels que les Rhizopus oryzae, ou similaire, dans une extraction à partir de la levure. Enfin, il est possible d'obtenir une composition comprenant un β－ＮＭＮ dérivée d'une levure en purifiant le β－ＮＭＮ provenant d'un liquide d'extraction de levure.
PCT/JP2017/018709 2016-05-19 2017-05-18 Extrait de levure riche en β－ｎｍｎ WO2017200050A1 (fr)

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019181961A1 (fr) * 2018-03-20 2019-09-26 三菱商事ライフサイエンス株式会社 MÉTHODE DE PRÉPARATION DE β-NMN ET COMPOSITION EN CONTENANT
WO2020129997A1 (fr) 2018-12-18 2020-06-25 帝人株式会社 Micro-organisme génétiquement modifié et procédé à la fois pour produire un dérivé de nicotinamide et un vecteur destiné à être utilisé dans celui-ci
JP2021008447A (ja) * 2019-07-01 2021-01-28 ベイジン サイエンスキュアキャンサー テクノロジー カンパニー リミテッド 成年女性、高齢者及び亜健康状態の人々に適用できる健康保持製品組成物
WO2021070829A1 (fr) 2019-10-11 2021-04-15 国立大学法人静岡大学 Bactéries d'acide lactique qui produisent du nicotinamide riboside, et bactéries d'acide lactique qui produisent du nicotinamide mononucléotide et du nicotinamide riboside
CN114099556A (zh) * 2020-08-25 2022-03-01 大江生医股份有限公司 富含烟酰胺单核苷酸的酵母粉、其制备方法及用途
WO2022138656A1 (fr) * 2020-12-25 2022-06-30 株式会社大阪ソーダ Procédé pour la production de nicotinamide mononucléotide

Citations (2)

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EP3770268A4 (fr) * 2018-03-20 2021-12-22 Mitsubishi Corporation Life Sciences Limited MÉTHODE DE PRODUCTION DE ß-NMN ET COMPOSITION EN CONTENANT
CN111954718A (zh) * 2018-03-20 2020-11-17 三菱商事生命科学株式会社 β-NMN的制造方法以及含有其的组合物
WO2019181961A1 (fr) * 2018-03-20 2019-09-26 三菱商事ライフサイエンス株式会社 MÉTHODE DE PRÉPARATION DE β-NMN ET COMPOSITION EN CONTENANT
JPWO2019181961A1 (ja) * 2018-03-20 2021-04-01 三菱商事ライフサイエンス株式会社 β―ＮＭＮの製造方法およびその含有組成物
JP7416684B2 (ja) 2018-03-20 2024-01-17 三菱商事ライフサイエンス株式会社 β―ＮＭＮの製造方法およびその含有組成物
WO2020129997A1 (fr) 2018-12-18 2020-06-25 帝人株式会社 Micro-organisme génétiquement modifié et procédé à la fois pour produire un dérivé de nicotinamide et un vecteur destiné à être utilisé dans celui-ci
KR20210091255A (ko) 2018-12-18 2021-07-21 데이진 가부시키가이샤 니코틴아미드 유도체를 제조하기 위한 재조합 미생물 및 방법, 그리고 그것에 사용되는 벡터
JP2021008447A (ja) * 2019-07-01 2021-01-28 ベイジン サイエンスキュアキャンサー テクノロジー カンパニー リミテッド 成年女性、高齢者及び亜健康状態の人々に適用できる健康保持製品組成物
WO2021070829A1 (fr) 2019-10-11 2021-04-15 国立大学法人静岡大学 Bactéries d'acide lactique qui produisent du nicotinamide riboside, et bactéries d'acide lactique qui produisent du nicotinamide mononucléotide et du nicotinamide riboside
CN114099556A (zh) * 2020-08-25 2022-03-01 大江生医股份有限公司 富含烟酰胺单核苷酸的酵母粉、其制备方法及用途
WO2022042615A1 (fr) * 2020-08-25 2022-03-03 大江生医股份有限公司 Poudre de levure riche en nicotinamide mononucléotide, procédé de préparation s'y rapportant et application associée
US11833116B2 (en) 2020-08-25 2023-12-05 Tci Co., Ltd. Preparation method of yeast powder rich in nicotinamide mononucleotide, yeast powder, and methods for improving skin condition, hair health, antiinflammation, cardiovascular health, antioxidation, antiaging and/or relieving body fatigue
WO2022138656A1 (fr) * 2020-12-25 2022-06-30 株式会社大阪ソーダ Procédé pour la production de nicotinamide mononucléotide

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