Classifications

• • 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
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
  • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
  • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
  • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
  • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
  • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
  • A61K35/66—Microorganisms or materials therefrom
  • A61K35/74—Bacteria
  • A61K35/741—Probiotics
  • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/60—Sugars; Derivatives thereof
  • A61K8/602—Glycosides, e.g. rutin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/67—Vitamins
  • A61K8/673—Vitamin B group
  • A61K8/675—Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
  • A61K8/99—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P39/00—General protective or antinoxious agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
• • 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; 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
  • C12N1/20—Bacteria; Culture media therefor
• • 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; 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
  • C12N1/20—Bacteria; Culture media therefor
  • C12N1/205—Bacterial isolates
• • 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
  • 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
  • C12P19/38—Nucleosides
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
  • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/10—General cosmetic use
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
  • A61K2800/805—Corresponding aspects not provided for by any of codes A61K2800/81 - A61K2800/95
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
  • A61Q19/08—Anti-ageing preparations
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
  • C12R2001/00—Microorganisms ; Processes using microorganisms
  • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales

Definitions

• the present invention relates to a lactic acid bacterium that produces nicotinamide riboside, and a lactic acid bacterium that produces nicotinamide mononucleotide and nicotinamide riboside.
• Non-Patent Documents 1 and 2 In recent years, aging and aging-related diseases have been shown to be closely associated with decreased levels of nicotinamide adenine dinucleotide (NAD + ) and decreased activity of the NAD + -dependent deacetylase sirtuin (NAD +).
• activation of sirtuins is thought to explain many of the effects of calorie restriction on life extension or health promotion (Non-Patent Document 2).
• NAD + has long been known as a coenzyme for redox reactions, but in recent years, it has also been known to play a role as a substrate for poly-ADP ribose polymerase, CD38 / CD157, sirtuin, etc. (Non-Patent Document 1). ). In particular, the decomposition reaction of NAD + to nicotinamide by sirtuins promotes the lysine residue deacetylation reaction by sirtuins that are coupled to it, and is involved in various life phenomena related to health and longevity (non-patented). Documents 1 and 2).
• NAMPT nicotinamide phosphoribosyl transferase
• Nicotinamide mononucleotides can be obtained from yeasts with eating experience such as torula yeast (Patent Document 1), and E. coli, B. coli, B. coli. B. subtilis, C.I. Glutamicum, A. glutamicum. A. bylyi, and R. It has been reported that nicotinamide riboside can be obtained from a genetically modified bacterium of a bacterium selected from the group consisting of R. europha (Patent Document 2).
• an object of the present invention is to provide a microorganism having a high production efficiency of nicotinamide riboside, and a microorganism capable of producing both nicotinamide mononucleotide and nicotinamide riboside.
• Item 1 A method for producing nicotinamide riboside, which comprises a step of culturing a lactic acid bacterium belonging to the genus Fructobacillus to prepare a culture containing nicotinamide riboside.
• Item 2. Item 2. The production method according to Item 1, wherein the culture is carried out in a medium containing no fructose.
• Item 3. The lactic acid bacteria are Fluctobacillus dulionis RD011272 strain (deposit number NITE-P02764), Fluctobacillus tropaeoil RD012353 strain (deposit number NITE P-02765), Fluctobacillus group Item 2.
• Item 1 or 2 which is selected from the above.
• Item 3. The production method according to Item 1 or 2, wherein the lactic acid bacterium is the Fructobacillus tropaeoil RD012353 strain (deposit number NITE P-02765) and / or the Fructobacillus fructosus NBRC3516 strain.
• Item 5. Contains a culture containing a nicotinamide riboside obtained from a lactic acid bacterium belonging to the genus Fructobacillus, a supernatant isolated from the culture, and / or a nicotinamide riboside isolated from the supernatant. , Nicotinamide riboside enhancer.
• the lactic acid bacteria are Fluctobacillus dulionis RD011272 strain (deposit number NITE-P02764), Fluctobacillus tropaeoil RD012353 strain (deposit number NITE P-02765), Fluctobacillus group Item 5.
• the strengthening agent according to Item 5 which is selected from the above.
• Item 7. Item 5.
• the strengthening agent according to Item 5, wherein the lactic acid bacterium is the Fructobacillus tropaeoil RD012353 strain (deposit number NITE P-02765) and / or the Fructobacillus fructosus NBRC3516 strain.
• a food or drink, cosmetic or pharmaceutical product containing the nicotinamide riboside enhancer according to any one of Items 5 to 7.
• Item 9. Fructobacillus dulionis RD011272 strain (deposit number NITE-P02764), Fructobacillus tropaeoil RD012353 strain (deposit number NITE P-02765), Fructobacillus tropaeu , A lactic acid bacterium that produces nicotinamide riboside.
• Item 10 A method for producing nicotinamide mononucleotide and nicotinamide riboside, which comprises a step of culturing a lactic acid bacterium belonging to the genus Fructobacillus.
• Item 10 The production method according to Item 10, wherein the culture is carried out in a medium containing fructose.
• the lactic acid bacteria are Fluctobacillus dulionis RD011272 strain (deposit number NITE-P02764), Fluctobacillus tropaeoil RD012353 strain (deposit number NITE P-02765), Fluctobacillus group Item 10.
• Item 13 Item 10.
• Item 14 A culture containing nicotinamide mononucleotide and nicotinamide riboside obtained from a lactic acid bacterium belonging to the genus Fructobacillus, a cell isolated from the culture, a crushed product of the cell, and / or the crushed product.
• the lactic acid bacteria are Fluctobacillus dulionis RD011272 strain (deposit number NITE-P02764), Fluctobacillus tropaeoil RD012353 strain (deposit number NITE P-02765), Fluctobacillus group Item 4.
• the strengthening agent according to Item 14 which is more selected.
• Item 17 A food or drink, cosmetic or pharmaceutical product containing the nicotinamide mononucleotide and the nicotinamide riboside enhancer according to any one of Items 14 to 16.
• Fructobacillus dulionis RD011272 strain (deposit number NITE-P02764), Fructobacillus tropaeoil RD012353 strain (deposit number NITE P-02765), Fructobacillus strain Nucleotide , Nicotinamide mononucleotide and nicotinamide riboside-producing lactic acid bacteria.
• Item 19 Nicotin of a culture containing nicotinamide riboside obtained from a lactic acid bacterium belonging to the genus Fructobacillus, a supernatant isolated from the culture, and / or a nicotinamide riboside isolated from the supernatant.
• amide riboside enhancers Use for the production of amide riboside enhancers.
• Item 20 A culture containing nicotinamide mononucleotide and nicotinamide riboside obtained from a lactic acid bacterium belonging to the genus Fructobacillus, a cell isolated from the culture, a crushed product of the cell, and / or the crushed product.
• lactic acid bacteria belonging to the genus Fluctobacillus are provided as microorganisms having high production efficiency of nicotinamide riboside and microorganisms capable of producing both nicotinamide mononucleotide and nicotinamide riboside. .. Therefore, a culture containing nicotinamide riboside or a culture containing nicotinamide mononucleotide and nicotinamide riboside, respectively, obtained from a lactic acid bacterium belonging to the genus Fructobacillus enhances nicotinamide riboside. It can be used as a food additive or a food additive that enhances nicotinamide mononucleotide and nicotinamide riboside.
• the method for producing nicotinamide riboside of the present invention is characterized by comprising a step of culturing a lactic acid bacterium belonging to the genus Fluctobacillus and preparing a culture containing nicotinamide riboside. And.
• the method for producing the nicotinamide riboside of the present invention will be described in detail.
• Lactic acid bacteria used in the production method of the present invention are not particularly limited as long as they are lactic acid bacteria belonging to the genus Fructobacillus. Lactic acid bacteria belonging to the genus Fructobacillus produce nicotinamide riboside.
• Examples of preferred lactic acid bacteria include Fluctobacillus dulionis, Fluctobacillus tropaeoil, and Fluctobacillus fructosus, preferably Fluctobacillus fructos from Fluctobacillus fructos. (Fructobacillus tropaeoil) and Fructobacillus fructosus.
• Examples of preferred lactic acid bacteria, Fructobacillus durionis RD011727 strain, Fructobacillus tropaeoil RD012353 strain, Fructobacillus tropaeoil RD012354 strain, Fructobacillus fructosus NBRC3516 strain, and Fructobacillus durionis NBRC113239 strain can be mentioned, more preferably, Fructobacillus durionis RD011727 strain, Fructobacillus tropaeoil RD012353 strain , Fluctobacillus tropaeoil RD012354 strain, and Fluctobacillus fructosus NBRC3516 strain.
• preferred lactic acid bacteria include Fluctobacillus fructosus and Fluctobacillus tropaeoil RD012353 strains. More preferably, Fructobacillus tropaeoil RD012353 strain and Fructobacillus fluctosus NBRC3516 strain are mentioned, and particularly preferably, Fructobacillus tropaeoil RD012353 strain is mentioned.
• the Fluctobacillus dulionis RD01172 strain was issued to the National Institute of Technology and Evaluation Patent Microorganisms Depositary Center (NPMD) (Room 122, 2-5-8 Kazusakamatari, Kisarazu City, Chiba Prefecture, Japan) on August 21, 2018. It has been deposited domestically as NITE-P02764.
• NPMD National Institute of Technology and Evaluation Patent Microorganisms Depositary Center
• Fructobacillus tropaeoil RD012353 strain was sent to the Patent Microorganisms Depositary Center (NPMD) (Room 122, 2-5-8 Kazusakamatari, Kisarazu City, Chiba Prefecture, Japan) on August 21, 2018. It has been deposited in Japan as NITE P-02765.
• NPMD Patent Microorganisms Depositary Center
• the Fluctobacillus RD012354 strain was sent to the Patent Microorganisms Depositary Center (NPMD) (Room 122, Kazusakamatari, Kisarazu City, Chiba Prefecture, Japan) on August 21, 2018. It has been deposited in Japan as NITE P-02766.
• NPMD Patent Microorganisms Depositary Center
• fructobacillus lactic acid bacteria strains one species may be used alone, or a plurality of species may be used in combination.
• the medium used for culturing lactic acid bacteria may be appropriately selected.
• the medium include those used for expansion culture (preculture medium) and those used for production culture (main culture medium).
• the main culture medium can be prepared based on the medium used as the pre-culture medium and further containing additives. Regarding the properties of the medium, it is preferably a liquid medium, but it may be an agar medium.
• the medium generally contains a nitrogen source, minerals and the like in addition to the carbon source.
• Examples of carbon sources include sugars and sugar materials.
• Examples of carbohydrates include sugars (monosaccharides, disaccharides, oligosaccharides), polysaccharides, and sugar alcohols.
• Examples of the sugar include lactose, sucrose, glucose, starch, xylitol, dextrose and the like.
• the sugar material may be an organic composition containing sugar, for example, milk and its processed products (skimmed milk powder, whey, milk powder, condensed milk, etc.), soymilk and its processed products (soymilk hydrolyzate, etc.), Examples include foods such as grains, fruits and vegetables.
• Milk includes those derived from any mammal such as cows, goats, sheep, buffaloes, camels, llamas, donkeys, yaks, horses and reindeer.
• the sugar may be isolated or contained in the sugar material.
• the fructose (sugar) may be in the form contained in the fruit (sugar material).
• One of these carbon sources may be used alone, or a plurality of types may be used in combination. Among these carbon sources, glucose is preferably mentioned.
• the medium does not contain fructose.
• the concentration of the carbon source in the medium is not particularly limited and may be appropriately set according to the type of medium, the culture method, etc., but for example, 0.5 to 4 w / w%, preferably 1 to 3 w / w%. More preferably, 1.5 to 2.5 w / w% can be mentioned.
• any inorganic nitrogen source or organic nitrogen source can be used.
• proteins such as yeast extract (brewer's yeast, etc.), meat extract, casein; protein hydrolysates such as peptone (protease peptone, etc.), peptides such as peptides; containing ammonium salts (ammonium citrate, etc.), nitrates, etc.
• nitrogen salts include nitrogen salts.
• One of these nitrogen sources may be used alone, or a plurality of types may be used in combination.
• the concentration of the nitrogen source in the medium is not particularly limited and may be appropriately set according to the type of medium, the culture method, etc., but in the case of protein, for example, 0.3 to 4 w / w%, preferably 0.5. 3 w / w%, more preferably 1-2 w / w%; in the case of peptides, for example 0.1-2 w / w%, preferably 0.3-1.8 w / w%, more preferably. 0.5 to 1.5 w / w%; in the case of nitrogen-containing salts, for example 0.03 to 1.5 w / w%, preferably 0.05 to 1 w / w%, more preferably 0.1 to 0.1 to 0.5 w / w% can be mentioned.
• Examples of minerals include manganese (manganesium sulfate, etc.), zinc, iron, sodium (sodium acetate, etc.), potassium (dipotassium hydrogensulfate, potassium phosphate, etc.), magnesium (magnesium sulfate, etc.), calcium, phosphorus (phosphate, etc.). (Potassium, etc.), sulfur (manganese sulfate, potassium hydrogen sulfate, magnesium sulfate, etc.), trace elements, etc. can be mentioned. These minerals may be used alone or in combination of two or more. Among these minerals, manganese, sodium, magnesium and potassium are preferable.
• the concentration of minerals in the medium is not particularly limited and may be appropriately set according to the type of medium, the culture method, etc., but in the case of manganese, for example, 0.001 to 0.01 w / w%, preferably 0. 003 to 0.008 w / w%; for sodium, for example 0.05 to 1.5 w / w%, preferably 0.1 to 1 w / w%; for magnesium, for example 0.001. To 0.02 w / w%, preferably 0.005 to 0.015 w / w%; in the case of potassium, for example 0.05 to 1 w / w%, preferably 0.1 to 0.5 w / w%. Can be mentioned.
• the medium includes vitamins (vitamin B group, etc.), surfactants (nonionic surfactants (Tween, etc.), anionic surfactants (SDS, etc.), etc.), antibacterial agents (triclosan, etc.). , Antibiotics (monesin, etc.) and other components may be included. These other components may be used alone or in combination of two or more. Among these other components, a surfactant is preferable, and a nonionic surfactant is more preferable.
• the concentration of other components in the medium is not particularly limited and may be appropriately set according to the type of other components, the type of medium, the culture method, etc., but when a surfactant is contained, the concentration of the surfactant Examples thereof include 0.01 to 0.5 w / w%, preferably 0.05 to 0.3 w / w%.
• a medium component approved as a food additive is selected from the above components. ..
• the method for culturing lactic acid bacteria of the genus Fructobacillus in the production method of the present invention is not particularly limited as long as the growth conditions of the lactic acid bacteria of the genus Fructobacillus can prepare a culture containing nicotinamide riboside.
• the culture temperature may be an optimum temperature of the lactic acid bacterium belonging to the genus Bacillus to be cultured, for example, 26 to 40 ° C, preferably 27 to 38 ° C, more preferably 28 to 36 ° C, and further preferably 29 to 34. °C is mentioned.
• the culturing time may be appropriately set according to the type of lactic acid bacterium belonging to the genus Bacillus to be actually cultivated, and examples thereof include 4 to 48 hours, preferably 8 to 36 hours, and more preferably 12 to 24 hours.
• the culture solution may be stirred during the culture of lactic acid bacteria in order to produce more nicotinamide riboside.
• the above-mentioned culture is carried out as a production culture (main culture) for a certain period of time, and before that, a small amount (for example, 1/6 to 1/4 of the main culture medium in terms of volume) is used.
• Expansion culture can be performed (preculture) at.
• the culture conditions for the pre-culture may be appropriately set according to the type of lactic acid bacteria of the genus Fructobacillus, and the above-mentioned conditions can be adopted.
• the culture obtained in the pre-culture may be inoculated into the main culture medium so that the OD660 is, for example, 0.01 to 0.04, preferably 0.01 to 0.03. it can.
• a culture containing the nicotinamide riboside obtained as described above is prepared.
• the culture may contain other Fructovacillus lactic acid bacteria metabolites co-produced in the culture.
• the culture containing the prepared nicotinamide riboside includes a form in which the prepared culture is used as it is, a form in which the supernatant is separated from the culture, and a form in which the supernatant is used as the nicotinamide riboside.
• the separation method include a centrifugal separation method and a membrane filtration method.
• the isolation method include various chromatography techniques such as ion exchange chromatography, gel filtration chromatography, reverse phase chromatography, and high performance liquid chromatography, salting out, and solvent precipitation.
• Nicotinamide riboside enhancer food and drink, cosmetics or pharmaceuticals
• the nicotinamide riboside can be suitably used as a nicotinamide riboside enhancer to be blended as an additive to foods for the purpose of fortifying nicotinamide riboside or as an active ingredient of cosmetics or pharmaceuticals.
• Nicotinamide riboside enhancer is a substance required for cells to utilize energy by nicotinamide riboside taken into the body by ingesting, taking or applying it in foods and drinks, cosmetics or pharmaceuticals. There are various useful effects by being converted to certain nicotinamide adenine dinucleotides.
• the nicotinamide riboside enhancer may contain other metabolites of the genus Bacillus lactic acid bacteria in addition to nicotinamide riboside.
• the nicotinamide riboside enhancer can be used as an enhancer of at least one of the other Fructobacillus lactic acid bacteria metabolites in addition to the nicotinamide riboside.
• nicotinamide riboside By adding a nicotinamide riboside enhancer to food and drink, nicotinamide riboside can be efficiently ingested by eating and drinking. As a result, health effects (calorie restriction, anti-aging, health promotion, etc.) due to ingestion of nicotinamide riboside can be expected.
• the food and drink includes not only food and drink for humans but also feed for animals.
• Foods and drinks are not particularly limited, and for example, beverages are not particularly limited, but are, for example, fermented milk (drink yogurt, etc.), lactic acid bacteria beverages, dairy beverages (coffee milk, fruit milk, etc.), and tea-based beverages (green tea). , Tea and Karyu tea, etc.), Fruit / vegetable beverages (beverages containing fruit juices such as oranges, apples, grapes, vegetable juices such as tomatoes, carrots), alcoholic beverages (beer, sparkling liquor, wine, etc.), carbonated beverages, Beverages such as soft drinks and water-based beverages; and foods such as fermented milk (set type yogurt, soft yogurt, etc.), confectionery, instant foods, processed foods such as seasonings, etc. may be mentioned.
• fermented milk lactic acid bacteria beverages
• dairy beverages coffee milk, fruit milk, etc.
• tea-based beverages green tea.
• Tea and Karyu tea, etc. Fruit / vegetable beverages (beverages containing fruit juices such as oranges, apples, grapes, vegetable juice
• Functional foods can also be mentioned as foods and drinks.
• Functional foods mean foods having a certain degree of functionality with respect to the living body, for example, foods for specified health use (including conditional foods [foods for specified health use]), foods with functional health such as nutritionally functional foods, and functions. Examples include sex-labeled foods, special-purpose foods, nutritional supplements, health supplements, supplements (for example, various dosage forms such as tablets, coated tablets, sugar-coated tablets, capsules and liquids) and beauty foods (for example, diet foods). ..
• the functional food may be a special-purpose food such as a food for the sick, a milk powder for pregnant women / lactating women, a prepared milk powder for infants, a food for the elderly, and a food for nursing care.
• nicotinamide riboside enhancer into cosmetics, pharmacological effects (prevention of aging, etc.) by nicotinamide riboside can be expected by application.
• cosmetics basic cosmetics such as lotion, milky lotion, cream, essence, gel, pack, sheet mask, lip cream; skin wash such as face wash, makeup remover (including cleansing agent), keratin remover, body shampoo, etc.
• nicotinamide riboside enhancer by adding the nicotinamide riboside enhancer to a pharmaceutical product, nicotinamide riboside can be taken orally or transdermally as an active ingredient by taking or applying it.
• the pharmacological effect of ingestion of nicotinamide riboside treatment or prevention of Cockayne syndrome and age-related diseases, treatment or prevention of oxidative damage to the skin, etc.
• Examples of pharmaceuticals include oral preparations and external preparations (including quasi-drugs). Dosage forms of oral preparations include tablets, coated tablets, sugar-coated tablets, capsules and liquid preparations, and dosage forms of external preparations include liquid preparations (including lotions, sprays, aerosols, and emulsions) and foams. Examples include agents, ointments, creams, gels, patches and the like.
• Mammals are preferably applied to foods and drinks, cosmetics or pharmaceuticals containing a nicotine amide riboside enhancer, for example, primates such as humans, chimpanzees and gorillas; dogs, cats, rabbits, cows, horses, etc. Pets or livestock such as pigs, goats, sheep and donkeys; experimental animals such as mice, rats, hamsters and monkeys.
• nicotinamide is cultivated under conditions under which a culture containing nicotinamide mononucleotide and nicotinamide riboside can be prepared under the growth conditions of fructobacillus lactic acid bacteria. Co-produces amide mononucleotide and nicotinamide riboside. This prepares a culture containing nicotinamide mononucleotide and nicotinamide riboside.
• lactic acid bacteria used in the method for producing nicotinamide mononucleotide and nicotinamide riboside are as described in "1. Method for producing nicotinamide riboside" above.
• examples of preferable lactic acid bacteria include Fluctobacillus dulionis, Fluctobacillus tropaeoil, and Fluctobacillus fructo.
• Examples of more preferable lactic acid bacteria include Fluctobacillus dulionis RD011272 strain, Fluctobacillus tropaeoil RD012353 strain, Fluctobacillus tropaeoil RD012354 strain, Fluctobacillus strain RD012354 strain, Fluctobacillus strain RD012354, and Fluctobacillus
• the amount of nicotinamide mononucleotide is increased (that is, the ratio of nicotinamide mononucleotide to nicotinamide riboside is higher).
• the lactic acid bacteria are preferably Fluctobacillus dulionis, Fluctobacillus fructosus, and Fluctobacillus trapaeoil RD012353. Dulionis), Fructobacillus fructosus, and more preferably Fluctobacillus dulionis RD01172, and Fructobacillus fructosus NBRC3516 strain.
• the lactic acid bacterium is preferably fructobacillus tropae oil ( Fructobacillus tropaeoil), preferably the Fructobacillus tropaeoil RD012353 strain.
• the medium used in the method for producing nicotinamide mononucleotide and nicotinamide riboside is as described in "1. Method for producing nicotinamide riboside" above, except that it is preferable that fructose is further contained as a carbon source. Is.
• the concentration of fructose in the medium is not particularly limited and may be appropriately set according to the type of medium, the culture method, etc., but for example, 0.5 to 4 w / w%, preferably 1 to 3.5 w / w%. , More preferably 1.5 to 2.5 w / w%.
• lactic acid bacteria belonging to the genus Fructose Bacillus accumulate nicotinamide riboside and nicotinamide riboside in the cells.
• the culture method and the like used in the method for producing nicotinamide mononucleotide and nicotinamide riboside are also as described in "1. Method for producing nicotinamide riboside" above. This produces both nicotinamide mononucleotides and nicotinamide ribosides.
• the use form of the culture containing both the prepared nicotinamide mononucleotide and nicotinamide riboside the form of using the prepared culture as it is, the form of separating the bacterial cells from the culture, and the bacterium. Examples thereof include a form in which the body is crushed and used, and a form in which nicotinamide riboside is isolated and used.
• Examples of the separation method include a centrifugal separation method and a membrane filtration method.
• Examples of the cell crushing method include a bead crushing method.
• Examples of the isolation method include various chromatography techniques such as ion exchange chromatography, gel filtration chromatography, reverse phase chromatography, and high performance liquid chromatography, salting out, and solvent precipitation.
• Nicotinamide mononucleotide and nicotinamide riboside enhancer food and drink, cosmetics or pharmaceuticals
• nicotinamide mononucleotide and a nicotinamide riboside enhancer can be blended as an additive to the above-mentioned food or as an active ingredient of cosmetics or pharmaceuticals.
• Nicotinamide mononucleotide and nicotinamide riboside enhancer are added to foods and drinks, cosmetics or pharmaceuticals, and when ingested, taken or applied, nicotinamide mononucleotide and nicotinamide riboside taken into the body are released into cells.
• Various useful effects can be achieved by converting to nicotinamide adenine dinucleotide, which is a substance necessary for utilizing energy.
• the nicotinamide mononucleotide and nicotinamide riboside enhancer may contain other lactic acid bacterium metabolites of the genus Fructobacillus in addition to nicotinamide mononucleotide and nicotinamide riboside.
• the nicotinamide mononucleotide and the nicotinamide riboside enhancer can be used as the enhancer of the other Fructovacillus lactic acid bacterium metabolite in addition to the nicotinamide mononucleotide and the nicotinamide riboside.
• nicotinamide mononucleotide and nicotinamide riboside By blending nicotinamide mononucleotide and nicotinamide riboside enhancer into food and drink, nicotinamide mononucleotide and nicotinamide riboside can be efficiently ingested by eating and drinking.
• nicotinamide mononucleotide and nicotinamide riboside enhancer are as described in "2. Nicotinamide riboside enhancer; food and drink, cosmetics or pharmaceuticals" above.
• the pharmacological effect of nicotinamide riboside prevention of aging, etc.
• the pharmacological effect of nicotinamide mononucleotide intracellular nicotinamide
• Increased mononucleotide, prevention of aging, etc. can be expected.
• Cosmetics containing nicotinamide mononucleotide and nicotinamide riboside enhancer are as described in "2. Nicotinamide riboside enhancer; food and drink, cosmetics or pharmaceuticals" above.
• the nicotinamide mononucleotide and the nicotinamide riboside enhancer of the food in the pharmaceutical product can be taken orally or transdermally as active ingredients by taking or applying. ..
• the pharmacological effect of ingestion of nicotinamide mononucleotide treatment or prevention of age-related diseases, etc.
• the pharmacological effect of ingestion of nicotinamide riboside treatment or prevention of cocaine syndrome and age-related diseases, etc., and skin oxidation
• Treatment or prevention of injury, etc. can be expected.
• the dosage form and application target of the drug containing the nicotinamide mononucleotide and the nicotinamide riboside enhancer are as described in "2. Nicotinamide riboside enhancer; food and drink, cosmetics or pharmaceuticals" above.
• Example 1 Production of nicotine amide riboside using lactic acid bacteria of the genus Fructobacillus Fluctobacillus cultures RD011272 strain (deposit number NITE-P02764), Fluctobacillus tropaeoil RD012353 strain (deposit number NITE P-0265 P-02766) and Fluctobacillus fructosus NBRC3516 strains were independently inoculated into 3 ml of MRS medium (preculture medium) manufactured by Difco, and expanded and cultured at 30 ° C. for 24 hours. The obtained culture broth was inoculated into 15 ml of MRS medium (main culture medium) so that the OD660 was 0.02, and produced and cultured at 30 ° C.
• MRS medium preculture medium
• main culture medium main culture medium
• Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) were quantified for each of the recovered culture supernatant and the recovered cells.
• nicotinamide mononucleotide and nicotinamide riboside are subjected to fluorescent derivatization treatment, analyzed under HPLC conditions described later, and the amount of nicotinamide mononucleotide and nicotinamide riboside produced in the supernatant (culture). The amount of production per liquid; mg / L) was measured. The results are shown in Table 1. In Table 1, n. d. Indicates that it was not detected.
• the recovered cells were washed with 10 ml of a 0.85 w / w% KCl aqueous solution. The washed cells were subjected to centrifugation again and the cells were collected. The recovered cells were suspended in 0.5 ml of 0.1 M potassium phosphate buffer (pH 7.0), an equal amount of 0.1 mm zirconia beads were added, and then the cells were crushed with a bead crusher. The crushed cells were separated by centrifugation, and the supernatant (crushed cell extract) was collected.
• NR nicotinamide riboside
• Example 2 Production of nicotinamide mononucleotide and nicotinamide riboside using lactic acid bacteria of the genus Fructobacillus Culturing and culturing in the same manner as in Example 1 except that 2 w / w% of fructose was added to the main culture medium. The supernatant and cells were collected, and nicotinamide mononucleotide and nicotinamide riboside were quantified. The results are shown in Table 2.
• nicotinamide mononucleotide (NMN) and nicotinamide mononucleotide (NMN) and nicotinamide riboside were both nicotinamide mononucleotide (NMN) and nicotinamide riboside from the Fluctobacillus tropaeoil RD012353 strain and the Fluctobacillus tropaeoil RD012354 strain, particularly from the Fluctobacillus tropaeoil RD012353 strain.
• nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are both produced together with nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR). It was confirmed that it was produced so that the ratio of NMN) was particularly high.

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• Organic Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Wood Science & Technology (AREA)
• Zoology (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Animal Behavior & Ethology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Biotechnology (AREA)
• Genetics & Genomics (AREA)
• Medicinal Chemistry (AREA)
• Molecular Biology (AREA)
• Microbiology (AREA)
• Epidemiology (AREA)
• General Engineering & Computer Science (AREA)
• Biochemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Pharmacology & Pharmacy (AREA)
• General Chemical & Material Sciences (AREA)
• Mycology (AREA)
• Tropical Medicine & Parasitology (AREA)
• Birds (AREA)
• Biomedical Technology (AREA)
• Virology (AREA)
• Food Science & Technology (AREA)
• Polymers & Plastics (AREA)
• Nutrition Science (AREA)
• Dermatology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Toxicology (AREA)
• Preparation Of Compounds By Using Micro-Organisms (AREA)
• Micro-Organisms Or Cultivation Processes Thereof (AREA)
• Coloring Foods And Improving Nutritive Qualities (AREA)

Priority Applications (7)

Applications Claiming Priority (2)

Related Child Applications (2)

Publications (1)

Family

ID=75436875

Family Applications (1)

Country Status (6)

Cited By (10)

Families Citing this family (2)

Citations (4)

Family Cites Families (9)

• 2020
  • 2020-10-06 KR KR1020227007600A patent/KR20220080075A/ko active Pending
  • 2020-10-06 US US17/642,626 patent/US20220340945A1/en active Pending
  • 2020-10-06 EP EP20875096.8A patent/EP4059571A4/en active Pending
  • 2020-10-06 CN CN202080063794.XA patent/CN114945677A/zh active Pending
  • 2020-10-06 JP JP2021551670A patent/JP7684906B2/ja active Active
  • 2020-10-06 WO PCT/JP2020/037902 patent/WO2021070829A1/ja not_active Ceased
• 2024
  • 2024-07-24 US US18/782,744 patent/US20240376508A1/en active Pending
• 2025
  • 2025-02-12 JP JP2025021095A patent/JP2025072615A/ja active Pending

Patent Citations (5)

Non-Patent Citations (8)

Also Published As

Similar Documents

Legal Events