WO2012063826A1 - Bacterium lactobacillus helveticus having high proteolysis activity - Google Patents
Bacterium lactobacillus helveticus having high proteolysis activity Download PDFInfo
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- WO2012063826A1 WO2012063826A1 PCT/JP2011/075735 JP2011075735W WO2012063826A1 WO 2012063826 A1 WO2012063826 A1 WO 2012063826A1 JP 2011075735 W JP2011075735 W JP 2011075735W WO 2012063826 A1 WO2012063826 A1 WO 2012063826A1
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- peptide
- lactic acid
- milk
- fermented milk
- amino acids
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Images
Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
- A23C9/123—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt
- A23C9/1234—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt characterised by using a Lactobacillus sp. other than Lactobacillus Bulgaricus, including Bificlobacterium sp.
-
- 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
- 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
- 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
- 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
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
-
- 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
- C12N1/20—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, 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
- C12N1/20—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
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/04—Alpha- or beta- amino acids
-
- 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
- C12P21/00—Preparation of peptides or proteins
- C12P21/06—Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products
-
- 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
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/11—Lactobacillus
- A23V2400/147—Helveticus
-
- 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
- C12R2001/225—Lactobacillus
Definitions
- the present invention relates to a novel lactic acid bacterium belonging to Lactobacillus helveticus. Moreover, this invention relates to the fermented milk obtained by fermenting this lactic acid bacterium, the composition containing this lactic acid bacterium, and food-drinks. Furthermore, the present invention relates to a method for producing amino acids and / or peptides using the lactic acid bacteria.
- Patent Document 5 YP as a functional peptide derived from milk other than VPP and IPP has been reported as having a blood pressure lowering action and an anxiolytic effect.
- IP, AP, EP, RP, QP, TP, MP, and GP which are dipeptides, are reported to be a group of peptides that are hardly degradable and have ACE inhibitory activity (for example, Patent Document 6).
- Lactobacillus helveticus (L. helveticus) has been conventionally used in the production of dairy products and is known to have high proteolytic activity.
- L. helveticus strains with high proteolytic activity and excellent peptide production have been reported (Patent Documents 1 to 4 and 7, Non-Patent Document 1). ).
- protein Since protein is composed of amino acids, it can be a source of amino acids by further degradation.
- Amino acids are known to have various functions other than nutrition and flavor.
- BCAA branched chain amino acids
- BCAA branched chain amino acids
- Alanine (Ala) is a glycogenic amino acid known as a liver energy source. Since NADH produced when alcohol is decomposed is consumed, it is thought that the decomposition reaction in the liver proceeds due to the presence of Ala. Ala is also known for its gustatory taste and masking effects such as salt, vinegar and egg taste.
- Lysine (Lys) is said to be the most deficient amino acid among the essential amino acids.
- Serine is important as a precursor of various important substances in vivo such as phosphatidylserine and other amino acids. In addition, it is known that it suppresses brain cell death such as lowering blood cholesterol and activating neurons in the brain, thereby preventing brain aging and moisturizing the skin.
- Microorganisms are actively used for such amino acid production.
- amino acids that can be ingested as a fermented product by microorganisms.
- Lactic acid bacteria are screened for lactic acid bacteria that have excellent degradation to amino acids for the purpose of affecting the flavor of pickles, but there are no known examples to examine functional amino acids and functional peptides in fermented milk itself .
- an object of the present invention is to provide a lactic acid bacterium having high proteolytic activity and excellent peptide production ability and / or amino acid production ability.
- Another object of the present invention is to provide fermented milk containing amino acids and / or peptides at a high concentration and having a good flavor.
- the present inventor is excellent in amino acid-producing ability and functional peptide-producing ability from milk protein, among lactic acid strains belonging to Lactobacillus helveticus, We succeeded in obtaining a strain having higher proteolytic activity.
- fermented milk and a composition having a high content of amino acids and / or peptides can be obtained, and the knowledge that amino acids and / or peptides can be produced is obtained to complete the present invention. It came.
- the present invention includes the following.
- a lactic acid bacterium belonging to Lactobacillus helveticus characterized by having at least one of the following properties (a) to (d):
- Fermented animal milk produces free amino acids of 25 ⁇ mol / ml or more
- Fermented animal milk produces peptides of 8.5 mg / ml or more
- XP peptide produced by fermenting animal milk And / or producing XPP peptide in a total amount of 260 ⁇ g / ml or more
- FERM BP-6060 The lactic acid bacterium according to any one of [1] to [5], which is a Lactobacillus helveticus CP3232 strain (Accession No. FERM BP-11271) or a mutant thereof.
- Lactobacillus helveticus CP3232 strain accesion number FERM BP-11271).
- a composition for producing amino acids and / or peptides from animal milk comprising at least one lactic acid bacterium belonging to Lactobacillus helveticus.
- the composition according to [9] or [10], wherein the free amino acid comprises at least one selected from alanine, lysine and serine.
- Any of [8] to [14], wherein the amount of IPP peptide and VPP peptide per acidity of fermented milk obtained by fermenting animal milk at 30 to 34 ° C. is 6.0 mg / g or more A composition according to 1.
- Fermented milk according to [17] which contains at least one lactic acid bacterium belonging to Lactobacillus helveticus.
- a method for obtaining a lactic acid bacterium belonging to Lactobacillus helveticus having proteolytic activity the following steps: (A) a step of preparing a mutant strain of Lactobacillus helveticus CM4 strain (Accession number FERM BP-6060) or Lactobacillus helveticus CP3232 strain (Accession number FERM BP-11271); and (b) from the mutant strain, The step of selecting a strain having at least one property of (a) to (d) of: (A) Fermented animal milk produces free amino acids of 25 ⁇ mol / ml or more (b) Fermented animal milk produces peptides of 8.5 mg / ml or more (c) XP peptide produced by fermenting animal milk And / or producing XPP peptide in a total amount of 260 ⁇ g / ml or more (d) The amount of IPP peptide and VPP peptide per acidity of ferment
- the manufacturing method of functional food / beverage products including the process of preparing a processed material, and the process of mix
- a lactic acid bacterium belonging to Lactobacillus helveticus having high proteolytic activity and excellent peptide production ability and / or amino acid production ability.
- the amino acids and / or peptides produced by this lactic acid bacterium have various functions.
- peptides such as IPP, VPP and YP have a blood pressure lowering action.
- fermented milk containing various amino acids and / or peptides having such various functions at a high concentration can be obtained by using the present lactic acid bacteria for fermentation.
- the amount of the IPP and VPP peptides per acidity of the obtained fermented milk is high, there is no problem due to the high acidity resulting from lactic acid produced with the progress of conventional fermentation. That is, since fermented milk containing a large amount of amino acids and / or peptides can be produced with respect to the amount of lactic acid produced, a small amount of fermented milk can be used to maintain a functionality and have a good flavor and easy to eat and drink. Products can be easily manufactured and provided to consumers.
- piece which amplified the genomic DNA derived from various lactic acid strains by polymerase chain reaction (PCR) method is shown.
- piece which amplified the genomic DNA derived from various lactic acid strains by polymerase chain reaction (PCR) method is shown.
- a lactic acid bacterium belonging to Lactobacillus helveticus according to the present invention is a kind of lactic acid bacterium that produces lactic acid from saccharides by fermentation, and is also referred to herein as “the lactic acid bacterium of the present invention”.
- the lactic acid bacterium of the present invention is characterized by having high proteolytic activity and excellent amino acid-producing ability and / or functional peptide-producing ability.
- the amount of IPP peptide and VPP peptide per acidity of fermented milk obtained by fermentation at 30 ° C. or more and 34 ° C. or less is 6.0 mg / g or more in terms of VPP.
- the above properties (a) to (d) can be determined by methods known in the art, for example, as described in Examples described later. Briefly, first, lactic acid bacteria belonging to Lactobacillus helveticus are fermented at 30 to 45 ° C., preferably 30 to 34 ° C. for 10 to 30 hours using milk protein (eg, animal milk) as a substrate, and the resulting milk protein fermentation is obtained.
- milk protein eg, animal milk
- the properties (a) to (d) can be determined by measuring the amount, acidity, etc. of free amino acids or peptides contained in the product.
- the amount of amino acid can be measured using a known amino acid analyzer, for example, high performance liquid chromatography.
- the lactic acid bacterium of the present invention produces free amino acids of 25 ⁇ mol / ml or more, preferably 30 ⁇ mol / ml or more by fermentation of animal milk. Further, a branched chain amino acid of 5 ⁇ mol / ml or more, more preferably 6 ⁇ mol / ml or 7 ⁇ mol / ml or more is generated, and 15% or more, more preferably 19% or 20% or more of the generated free amino acids are branched. It is preferably an amino acid (valine, leucine, isoleucine).
- the free amino acid preferably contains at least one selected from alanine, lysine and serine at 2000 ⁇ g / ml or more, and preferably contains at least two amino acids at 1500 ⁇ g / ml.
- the amount of peptide can be measured using methods known in the art, such as the OPA method (Church et al., J. Dairy Sci. 1983. 66: 1219-1227).
- the lactic acid bacteria of the present invention are those that produce peptides of 8.5 mg / ml or more, preferably 10 mg / ml or more by fermentation of animal milk.
- XP peptide means a peptide composed of Xaa-Pro (Xaa is any amino acid), and XP peptide includes, for example, YP (Tyr-Pro), VP (Val-Pro), IP (Ile-Pro), AP (Ala-Pro), EP (Glu-Pro), RP (Arg-Pro), QP (Gln-Pro), TP (Thr-Pro), MP (Met-Pro) and GP ( Gly-Pro).
- the XPP peptide means a peptide composed of Xaa-Pro-Pro (Xaa is any amino acid). Examples of the XPP peptide include VPP (Val-Pro-Pro) and IPP (Ile-Pro-Pro).
- XP peptides and XPP peptides are also referred to as dipeptides and tripeptides, respectively, and collectively referred to as “functional peptides”.
- the amount of XP peptide and / or XPP peptide can be measured using a known LC / MS apparatus.
- the lactic acid bacterium of the present invention produces XP peptide and / or XPP peptide in a total amount of 260 ⁇ g / ml or more, preferably 280 ⁇ g / ml or more, more preferably 300 ⁇ g / ml or more by fermentation of animal milk.
- the acidity (acid concentration in the fermented milk) can be measured by a known neutralization titration method, for example, using a known automatic titration apparatus.
- IPP peptide and VPP peptide can be measured by the method described regarding (c).
- the amount of IPP peptide and VPP peptide per acidity of fermented milk obtained by fermenting animal milk at 30 ° C. to 34 ° C. is 5.5 mg / ml or more, preferably 6.0 mg / ml in terms of VPP. More than ml.
- the said amount is calculated as fermented milk specific gravity 1.02.
- VPP conversion amount ⁇ g / ml IPP amount ( ⁇ g / ml) ⁇ 1.7 + VPP amount ( ⁇ g / ml)
- the lactic acid bacterium of the present invention has at least one of the above properties (a) to (d), and lactic acid bacterium exhibiting two, three or all of the above properties is preferable.
- the lactic acid bacteria of the present invention have the properties (a), (b), (c) or (d), or (a) and (b), (a) and (c), (a) and (D), (b) and (c), (b) and (d), or (c) and (d), or (a), (b) and (c), (a) And (b) and (d), (a) and (c) and (d), (b), (c) and (d), or (a) to (d) Is.
- any lactic acid bacterium belonging to Lactobacillus helveticus exhibiting at least one of the properties described above is included in the lactic acid bacterium of the present invention.
- the present inventors have independently selected a lactobacillus helveticus CM4 strain (Accession No. FERM BP-6060, Patent Document 1) from a mutant strain obtained as a parent strain. Bacillus helveticus CP3232 strain.
- the Lactobacillus helveticus CM4 and CP3232 strains were registered by the applicant of the Patent Organism Depositary Center (Ibaraki, Japan), an independent administrative agency, National Institute of Advanced Industrial Science and Technology, which is an international depositary authority based on the Budapest Treaty for deposit of patent microorganisms.
- the Lactobacillus helveticus CP3232 strain has been confirmed to have all the properties (a) to (d) described above in the Examples.
- the Lactobacillus helveticus CP3232 strain is a mutant derived from the parent strain Lactobacillus helveticus CM4 as described above. Therefore, the mutant strains of the Lactobacillus helveticus CM4 strain and the Lactobacillus helveticus CP3232 strain have a high probability of having any of the above properties (a) to (d). Such a mutant strain derived from Lactobacillus helveticus CP3232 strain or Lactobacillus helveticus CM4 strain is also included in the present invention as long as it has the above properties.
- mutant strain means any strain obtained from the parent strain. Specifically, it is obtained by a method of artificially increasing the frequency of mutation from a parent strain by natural mutation or induced mutation by a chemical or physical mutagen, or by a specific mutagenesis technique (for example, gene recombination). Means a stock. A microbial individual produced by such a method is repeatedly selected and separated, and a useful microbial individual is bred to obtain a mutant having the desired properties.
- “Mutant strains as used herein include CM4 strain, CP3232 strain or strains obtained by using the mutant strain as a parent strain. That is, the mutant strain selected by performing several mutation treatments on the CM4 strain is also included in the mutant strain of the CM4 strain.
- mutant strains derived from Lactobacillus helveticus CM4 strain, Lactobacillus helveticus CP3232 strain and mutant strains of other lactobacillus strains by molecular weight distribution of the amplified fragment of lactic acid bacteria genomic DNA by polymerase chain reaction (PCR) method And can be easily identified.
- PCR polymerase chain reaction
- a DNA sample is prepared, for example, gene amplification is performed by PCR using primers having the sequences shown in SEQ ID NOs: 1 and 2, and the electrophoresis pattern of the obtained fragment is obtained.
- the method for confirming whether or not it is a mutant strain is not limited to this method, and even if the above PCR fragment is not detected, a mutant strain derived from the Lactobacillus helveticus CM4 strain, It may be a mutant strain of Bacillus helveticus CP3232, and it can be confirmed whether it is a mutant strain by a method known in the art such as detection of other gene fragments or mycological properties.
- the lactic acid bacteria of the present invention can be prepared by culturing under suitable conditions using a medium usually used for culturing lactic acid bacteria.
- a medium usually used for culturing lactic acid bacteria contains a carbon source, a nitrogen source, inorganic salts, and the like and can culture lactic acid bacteria efficiently, either a natural medium or a synthetic medium may be used. If so, a known medium suitable for the strain to be used can be appropriately selected. Lactose, glucose, galactose, molasses, etc. can be used as the carbon source, and organic nitrogen-containing substances such as casein hydrolyzate, whey protein hydrolyzate, and soy protein hydrolyzate are used as the nitrogen source. be able to.
- inorganic salts phosphates, sodium, potassium, magnesium and the like can be used.
- a medium suitable for culturing lactic acid bacteria include MRS liquid medium, GAM medium, BL medium, Briggs Liver Broth, animal milk, skim milk, and milky whey.
- a milk medium containing sterilized skim milk is used.
- the lactic acid bacteria of the present invention are cultured at 20 to 50 ° C., preferably 25 to 42 ° C., more preferably 28 to 37 ° C. under anaerobic conditions.
- the temperature condition can be adjusted by a thermostatic bath, a mantle heater, a jacket, or the like.
- the anaerobic condition means a low oxygen environment in which lactic acid bacteria can grow.
- an anaerobic chamber, an anaerobic box, a sealed container or bag containing an oxygen scavenger, or the like is used.
- Anaerobic conditions can be achieved by sealing the culture vessel.
- the culture format is stationary culture, shake culture, tank culture, or the like.
- the culture time can be 3 to 96 hours.
- the pH of the medium at the start of the culture is preferably maintained at 4.0 to 8.0.
- lactic acid bacteria of the present invention A specific preparation example of the lactic acid bacteria of the present invention will be briefly described.
- lactic acid bacteria are inoculated at a rate of about 5% in a sterilized milk medium (such as a milk medium containing 9.00% (w / w) reduced skim milk powder) Incubate overnight (about 18-28 hours) at °C. It is preferable to repeat this culture operation.
- the obtained culture may be used as it is, or may be subjected to solid-liquid separation and / or sterilization by filtration and / or filtration if necessary.
- the processed product of the lactic acid bacterium obtained by processing the lactic acid bacterium of the present invention may be used, or the processed product of the lactic acid bacterium may be further processed.
- An example of such processing is described below.
- Fermented products can be prepared by fermenting raw milk, skim milk or soy milk using lactic acid bacteria cells and / or processed products.
- lactic acid bacteria or other treated lactic acid bacteria are inoculated into raw milk, skim milk, or soy milk, and fermented under lactic acid bacteria fermentation conditions known in the art (substantially the same as the lactic acid bacteria culture conditions described above).
- the obtained fermented product may be used as it is, or may be subjected to other treatments such as filtration, sterilization, dilution and concentration.
- It can be prepared as a suspension or dilution by suspending or diluting lactic acid bacteria and / or treated products in an appropriate solvent.
- solvent examples include water, physiological saline, phosphate buffered saline (PBS), and the like.
- Lactic acid bacteria and / or treated products can be prepared as a sterilized product by sterilization.
- known sterilization processes such as filtration sterilization, radioactive sterilization, superheated sterilization, and pressure sterilization can be performed.
- the lactic acid bacteria and / or the treated product are treated at a high temperature (for example, 80 to 150 ° C.) for a certain period of time, for example, about 10 minutes to 1 hour (for example, about 10 to 20 minutes). .
- a high temperature for example, 80 to 150 ° C.
- a certain period of time for example, about 10 minutes to 1 hour (for example, about 10 to 20 minutes).
- a crushed product and a cell-free extract can be prepared.
- crushing can be performed by physical crushing (stirring, filter filtration, etc.), enzyme dissolution treatment, chemical treatment, or autolysis treatment.
- Extracts can be obtained by extracting lactic acid bacterial cells and / or processed products using an appropriate aqueous or organic solvent.
- the extraction method is not particularly limited as long as it is an extraction method using an aqueous solvent or an organic solvent as an extraction solvent. And a known method such as a method of immersing, stirring or refluxing in ethanol).
- the microbial cell of lactic acid bacteria and / or a processed material can be dried, and can be made into a powdery material (powder) or a granular material.
- a powdery material for example, spray drying, drum drying, vacuum drying, freeze-drying etc. are mentioned, These can be employ
- the lactic acid bacterium of the present invention may be a wet cell or a dry cell.
- the lactic acid bacteria and / or processed product obtained above can be used alone or together with other components as a composition for producing amino acids and / or peptides from animal milk. That is, the present invention provides a composition for producing amino acids and / or peptides, which contains at least one lactic acid bacterium belonging to Lactobacillus helveticus.
- the composition of the present invention is capable of producing free amino acids of 25 ⁇ mol / ml or more, preferably 30 ⁇ mol / ml or more by fermenting animal milk. Preferably, 15% or more of the free amino acids produced are branched chain amino acids. Alternatively or additionally, the composition of the present invention is capable of producing 8.5 mg / ml or more, preferably 10 mg / ml or more of peptide by fermenting animal milk. Alternatively or in addition, the composition of the present invention produces XP peptide and / or XPP peptide in a total amount of 260 ⁇ g / ml, preferably 280 ⁇ g / ml, more preferably 300 ⁇ g / ml by fermenting animal milk.
- composition of the present invention is such that the amount of IPP peptide and VPP peptide per acidity of fermented milk obtained by fermenting animal milk at 30 ° C. or more and 34 ° C. or less is 6.0 mg / g or more in terms of VPP. It will be.
- the composition of the present invention contains the above-mentioned lactic acid bacteria and / or treated product as an active ingredient, but may contain one kind of lactic acid bacteria and / or treated product, a plurality of different lactic acid bacteria and / or treated products, A plurality of processed lactic acid bacteria that have been subjected to different treatments may be included in combination.
- the composition of the present invention preferably contains 1 ⁇ 10 7 cells / ml or more of lactic acid bacteria.
- composition of the present invention may be added with additives and excipients known in the art alone or in combination, as long as the intended action is not inhibited. Good. Further, the composition of the present invention may contain an additive (for example, sugar such as glutamic acid or glucose) that promotes fermentation of lactic acid bacteria.
- an additive for example, sugar such as glutamic acid or glucose
- the form of the composition of the present invention is not particularly limited, and may be a suspension, granule, powder, capsule or the like.
- the content of the active ingredient (lactic acid bacteria) in the composition of the present invention varies depending on the form, but the amount of lactic acid bacteria is usually 0.0001 to 99% by mass, preferably 0.001 to 80% by mass, more preferably 0.001 to It is in the range of 75% by mass.
- the number of lactic acid bacteria contained in the composition of the present invention is about 10 7 / g to about 10 12 / g.
- the present invention is obtained by fermenting animal milk using at least one lactic acid bacterium belonging to Lactobacillus helveticus, comprising at least one component of the following (a) to (d): Provide fermented milk with: (A) 25 ⁇ mol / ml or more, preferably 30 ⁇ mol / ml free amino acids (of which 15% or more are preferably branched chain amino acids) (B) Peptide of 8.5 mg / ml or more, preferably 10 mg / ml or more (c) XP peptide and / or XPP peptide (c) in a total amount of 260 ⁇ g / ml or more, preferably 280 ⁇ g / ml or more, more preferably 300 ⁇ g / ml or more d) V
- the fermented milk of the present invention can be prepared by performing a fermentation treatment according to a method known in the art using the lactic acid bacteria or composition of the present invention.
- the fermentation treatment can be performed by adding at least one lactic acid bacterium to animal milk and culturing under appropriate conditions.
- animal milk milk derived from mammals such as cow's milk, goat's milk, and horse milk, or processed milk such as skim milk, reduced milk, condensed milk, etc. can be used, even if one kind of milk is used. It is also possible to use a combination of multiple types of milk and processed milk.
- the solid content concentration of milk is not particularly limited. For example, when skim milk is used, the solid content concentration of nonfat milk is about 3 to 15% by mass, preferably 6 to 15% by mass.
- Animal milk may be sterilized before the fermentation treatment.
- the animal milk may be added with an additive that promotes fermentation of lactic acid bacteria (for example, sugar such as glutamic acid or glucose).
- an additive that promotes fermentation of lactic acid bacteria for example, sugar such as glutamic acid or glucose.
- the lactic acid bacterium added to the animal milk is preferably a pre-cultured lactic acid bacterium used as a starter.
- the amount of lactic acid bacteria to be added is not limited, but is usually 0.005 to 10% by mass, preferably 0.05 to 5% by mass in terms of dry lactic acid bacteria.
- the lactic acid bacterium to be used may be a lactic acid bacterium culture as it is, or the cultured lactic acid bacterium may be separated from the medium by filtration or centrifugation, and stored after freezing or lyophilized after separation from the medium. It may be the one you have left.
- the conditions for the fermentation treatment are almost the same as the above-mentioned culture conditions for lactic acid bacteria, and are carried out under anaerobic conditions at 20 ° C. to 50 ° C., preferably 25 ° C. to 42 ° C., more preferably 28 ° C. to 37 ° C.
- the lactic acid bacteria of the present invention produced particularly many branched chain amino acids and functional peptides at 30 to 34 ° C. (about 32 ° C.). Therefore, it is particularly preferable to perform the fermentation treatment at 30 to 34 ° C.
- the temperature condition can be adjusted by a thermostatic bath, a mantle heater, a jacket, or the like.
- the fermentation treatment can be carried out in a form such as stationary culture, shake culture, tank culture or the like.
- the fermentation time can be 3 to 96 hours, preferably 12 to 36 hours. Fermentation is preferably performed while measuring the pH and acidity of the fermenter, and the pH is preferably maintained at 4.0 to 8.0.
- the fermented milk obtained as described above contains a desired component
- the fermented milk may be processed, or the processed product of the fermented milk may be further processed.
- An example of such processing is described below.
- It can be prepared as a suspension or dilution by suspending or diluting fermented milk and / or processed fermented milk in a suitable solvent.
- suitable solvent examples include water, physiological saline, phosphate buffered saline (PBS), and the like.
- fermented milk and / or fermented milk processed product By sterilizing fermented milk and / or fermented milk processed product, it can be prepared as a sterilized processed product.
- known sterilization processes such as filtration sterilization, radioactive sterilization, superheated sterilization, and pressure sterilization can be performed.
- It can be prepared as a heat-treated product by heat-treating the fermented milk and / or the fermented milk-treated product.
- high temperature treatment for example, 80 to 150 ° C.
- a certain period of time for example, about 10 minutes to 1 hour (for example, about 10 to 20 minutes).
- the supernatant can be prepared by filtering or centrifuging fermented milk and / or processed fermented milk.
- the fermented milk and / or processed fermented milk can be dried to obtain a powdery product (powder) or a granular product.
- a powdery product for example, spray drying, drum drying, vacuum drying, freeze-drying etc. are mentioned, These can be employ
- the fermented milk or processed product of the present invention contains various amino acids and / or peptides at a high concentration, it can be used for applications utilizing the properties of the amino acids and / or peptides.
- amino acids are involved in flavor, energy source, tranquilizing action, growth promoting action, etc.
- the fermented milk of the present invention can be used as a flavor improving agent, nutritional supplement, and energy supplement.
- branched chain amino acids (BCAA) containing valine, leucine and isoleucine are essential amino acids and can be used for muscle strengthening and physical fatigue prevention.
- BCAA branched chain amino acids
- Lysine is said to be the most deficient amino acid among essential amino acids, and must be taken as a material for antibodies, hormones, enzymes, and the like. Lys has also been reported to be associated with calcium absorption, collagen formation, and bone tissue production.
- Serine is important as a precursor of various important substances in vivo such as phosphatidylserine and other amino acids. In addition, it is known that it suppresses brain cell death such as lowering blood cholesterol and activating neurons in the brain, thereby preventing brain aging and moisturizing the skin.
- the fermented milk or processed product of the present invention is a flavor improving agent, nutritional supplement, energy supplement, brain function improving agent, autonomic nerve regulator, parasympathetic nerve regulator, sympathetic nerve regulator, muscle degradation / damage inhibitor. , Muscle strengthening agents, fatigue relieving agents, endurance improving agents, alcohol metabolizing agents and the like.
- VPP peptide and IPP peptide have ACE inhibitory activity and relaxing effect
- LPP peptide has ACE inhibitory activity
- YP peptide has blood pressure lowering action and anxiolytic action
- VP, IP, AP, EP, RP Since QP, TP, MP and GP peptides are non-degradable in vivo and have ACE inhibitory activity
- the fermented milk or processed product of the present invention can be used as an antihypertensive agent and a stress relieving agent.
- amino acids and / or peptide components or fractions containing these components may be purified from the obtained fermented milk or processed product thereof using a known separation / purification method.
- the fermented milk or processed product thereof according to the present invention includes at least one component (for example, amino acid, peptide) among the components (a) to (d) described above, but may include a combination of a plurality of components.
- the lactic acid bacteria used for the fermentation process may be contained in fermented milk or its processed material.
- the fermented milk of the present invention has additives, which will be described later, other known antihypertensive agents, stress relieving agents, nutritional supplements, energy supplements, muscle potentiators, flavor improvers, as long as the intended action is not inhibited. These may be added singly or in combination.
- the form of the fermented milk of the present invention is not particularly limited.
- the form of a suspension as a fermented milk obtained after fermentation treatment, as well as tablets, capsules obtained by processing by techniques known in the art It can be in the form of granules, powder, powder, syrup, dry syrup and the like.
- the fermented milk is preferably in a form that can be easily administered or ingested orally.
- a liquid such as a suspension may be in a form suspended in water or other suitable medium immediately before administration or ingestion.
- the surface is coated by a known method. May be.
- the fermented milk of the above-described form is a commonly used excipient, disintegrant, binder, wetting agent, stabilizer, buffer, lubricant, preservative, surfactant, fermented milk obtained by fermentation treatment, Additives such as sweeteners, flavoring agents, fragrances, acidulants, and coloring agents can be blended and manufactured according to conventional methods. For example, when fermented milk is used for the purpose of medicine or health promotion, a pharmaceutically acceptable carrier or additive can be blended.
- Such pharmaceutically acceptable carriers and additives include water, pharmaceutically acceptable organic solvents, collagen, polyvinyl alcohol, polyvinyl pyrrolidone, carboxyvinyl polymer, sodium alginate, water soluble dextran, water soluble dextrin , Sodium carboxymethyl starch, pectin, xanthan gum, gum arabic, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol, petrolatum, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol, lactose, pharmaceutical additives And an acceptable surfactant.
- the fermented milk of the present invention may coexist with various additives and other various substances used in the production of pharmaceuticals, foods and drinks, and feeds.
- substances and additives include various fats and oils (for example, vegetable oils such as soybean oil, corn oil, safflower oil, olive oil, animal fats such as beef tallow and sardine oil), herbal medicines (eg royal jelly, carrots, etc.), Amino acids (eg, glutamine, cysteine, leucine, arginine, etc.), polyhydric alcohols (eg, ethylene glycol, polyethylene glycol, propylene glycol, glycerin, sugar alcohols such as sorbitol, erythritol, xylitol, maltitol, mannitol, etc.), natural polymers (For example, gum arabic, agar, water-soluble corn fiber, gelatin, xanthan gum, casein, gluten or gluten hydrolyzate, lecithin, starch, dextrin
- taurine, glutathione, carnitine, creatine, coenzyme Q, glucuronic acid, glucuronolactone, pepper extract, ginger extract, cacao as functional ingredients or additives other than the above active ingredients
- Contains extract, guarana extract, garcinia extract, theanine, ⁇ -aminobutyric acid, capsaicin, capsiate, various organic acids, flavonoids, polyphenols, catechins, xanthine derivatives, resistant oligosaccharides such as fructooligosaccharides, polyvinylpyrrolidone, etc. can do.
- the amount of these additives is appropriately determined according to the type of additive and the amount of intake that should be desired.
- the subjects to administer or ingest the fermented milk of the present invention are vertebrates, specifically mammals such as humans, primates (monkeys, chimpanzees, etc.), livestock animals (cow, horses, pigs, sheep, birds, etc.) ), Pet animals (dogs, cats, etc.), laboratory animals (mouse, rats, etc.), reptiles and birds.
- mammals such as humans, primates (monkeys, chimpanzees, etc.), livestock animals (cow, horses, pigs, sheep, birds, etc.) ), Pet animals (dogs, cats, etc.), laboratory animals (mouse, rats, etc.), reptiles and birds.
- Particularly preferred are subjects for which intake of amino acids and / or peptides is desired, such as hypertensive patients, humans who exhibit symptoms due to stress, and humans before and after exercise.
- the administration or intake of the fermented milk of the present invention varies depending on the age and weight of the subject, the administration / intake route, the administration / ingestion frequency, the purpose of administration, etc. Can be changed.
- the content ratio of the active ingredient contained in the fermented milk is not particularly limited, and may be appropriately adjusted according to the ease of production, the preferable daily dose, and the like. Since the fermented milk of the present invention is highly safe, the intake can be further increased.
- the daily intake may be taken once, but may be taken in several divided doses.
- the frequency of administration or ingestion is not particularly limited, and can be appropriately selected according to the administration / intake route, the age and weight of the subject, and various conditions of the intended effect.
- the administration / intake route of the fermented milk of the present invention is not particularly limited, but oral administration or ingestion is preferred.
- oral administration or ingestion is preferred.
- it can be orally administered or taken in a food or drink or feed, or as a tablet or granule.
- the fermented milk of the present invention may be used in combination with other medicines, treatment or prevention methods.
- Such other medicaments may form one preparation together with the fermented milk of the present invention, or may be administered as separate preparations at the same time or at intervals.
- the fermented milk of the present invention includes a blood pressure lowering agent, a brain function improving agent, an autonomic nerve regulator, a parasympathetic nerve regulator, a sympathetic nerve regulator, a nutritional supplement, an energy supplement, a muscle degradation / damage inhibitor. It can be used as a muscle strengthening agent, fatigue relieving agent, endurance improving agent, flavor improving agent, alcohol metabolizing agent and the like.
- the lactic acid bacteria and fermented milk of the present invention are safe and easy to take for a long time, they can be used for food and drink and feed.
- the lactic acid bacterium of the present invention produces many amino acids and / or peptides having various functions, and the fermented milk of the present invention contains such amino acids and / or peptides at high concentrations.
- the lactic acid bacterium of the present invention has a high production amount of functional peptide with respect to acidity, and can suppress acidity, and even when added to various foods and drinks, it does not inhibit the taste of the foods and drinks themselves. Therefore, the lactic acid bacteria and fermented milk of the present invention can be added continuously to various foods and drinks, and various effects are expected.
- the food or drink of the present invention contains at least one lactic acid bacterium of the present invention and / or a processed product thereof and / or fermented milk of the present invention and / or a processed product thereof.
- drinks are also included in the food and drink. All the foods and drinks which can mix
- a functional food or drink is particularly preferable.
- the “functional food / beverage” of the present invention means a food / beverage having a certain functionality with respect to a living body.
- a food / beverage for specified health use including conditional tokuho [food for specified health]) and nutritional function Health function foods and drinks including foods and drinks, special purpose foods and drinks, nutritional supplement foods and drinks, health supplement foods and drinks, supplements (for example, tablets, coated tablets, dragees, capsules, liquids, etc.) and beauty foods and drinks
- so-called health foods and beverages such as diet foods and beverages are included.
- foods and drinks include liquid foods such as tube enteral nutrients, healthy foods and drinks in the form of preparations such as tablet confections, tablets, chewable tablets, tablets, powders, powders, capsules, granules and drinks, and Nutritional supplement food and drink; tea beverages such as green tea, oolong tea and black tea, soft drinks, jelly drinks, sports drinks, milk drinks, carbonated drinks, vegetable drinks, fruit juice drinks, fermented vegetable drinks, fermented fruit juice drinks, fermented milk drinks, fermented milk (Drink yogurt, solid yogurt), fermented milk beverage (sterilized), lactic acid bacteria beverage, concentrated type beverage, concentrated solid, milk beverage (such as coffee milk), powdered beverage, cocoa beverage, milk and beverages such as purified water; butter, Spreads such as jam, sprinkles and margarine; mayonnaise, shortening, custard cream, dressings, breads, cooked rice, noodles, pasta, taste Juice, tofu, yogurt, soup or sauces, confectionery products (for example, biscuits and cookies such, chocolate,
- the food and drink of the present invention include other food materials, various nutrients, various vitamins, minerals, dietary fiber, various additives (for example, used in the production of the food and drink)
- a taste component, a sweetener, an acidulant such as an organic acid, a stabilizer, a flavor) and the like can be blended and manufactured according to a conventional method.
- the amount of lactic acid bacteria, fermented milk, or a processed product thereof can be appropriately determined by those skilled in the art in consideration of the form of the food / beverage products and the required taste or texture.
- the food and drink of the present invention in a form that can manage the desired intake, blood pressure lowering, stress relaxation, nutritional supplementation, energy assistance, muscle enhancement, brain function improvement, and autonomic nerves using the food and drink Methods such as regulation, parasympathetic regulation, sympathetic regulation, muscle degradation / damage inhibition, muscle augmentation, reduction of fatigue, endurance, and alcohol metabolism are provided.
- the food and drink of the present invention can be manufactured by any appropriate method available to those skilled in the art.
- the lactic acid bacteria and / or fermented milk (processed product) of the present invention can be prepared in a liquid form, a gel form, a solid form, a powder form, or a granule form, and then blended into a food or drink. Or you may mix or melt
- Lactic acid bacteria and / or fermented milk may be uniformly dispersed in food and drink, or may be unevenly distributed. Capsules containing lactic acid bacteria and / or fermented milk (processed product) may be prepared. Lactic acid bacteria and / or fermented milk (processed product) may be wrapped with an edible film or an edible coating agent. Moreover, after adding a suitable excipient
- the food and drink of the present invention may be further processed, and such processed products are also included in the scope of the present invention.
- Additives include, but are not limited to, color formers (sodium nitrite, etc.), colorants (cuttlefish pigment, red 102, etc.), flavorings (orange flavors, etc.), sweeteners (stevia, aspartame, etc.), preservatives (Sodium acetate, sorbic acid, etc.), emulsifiers (sodium chondroitin sulfate, propylene glycol fatty acid ester, etc.), antioxidants (disodium EDTA, vitamin C, etc.), pH adjusters (citric acid, etc.), chemical seasonings (inosinic acid) Sodium), thickeners (xanthan gum, etc.), swelling agents (calcium carbonate, etc.), antifoaming agents (calcium phosphate, etc.), binders (sodium polyphosphate, etc.), nutrient enhancers (calcium fort)
- the food / beverage products of the present invention have various functions attributable to amino acids and / or peptides, as described above, and are highly safe and free from side effects. Moreover, the lactic acid bacteria and / or fermented milk of the present invention can suppress acidity, have a good flavor, and do not inhibit the flavor of the food or drink even when added to various food or drink. The obtained food and drink can be easily taken continuously for a long time, and various functions are expected to be exhibited over a long period of time.
- the lactic acid bacteria and / or fermented milk of the present invention can be blended not only in human foods and drinks but also in animal feeds for livestock (cattle, pigs, etc.), racehorses, pets (dogs, cats, etc.). . Since the feed is almost the same as the food and drink except that the subject is other than a human, the above description regarding the food and drink can be similarly applied to the feed.
- Example 1 Identification of L. helveticus CP3232 strain
- L. helveticus CM4 strain (Accession No. FERM BP-6060) was bred and novel mutants having the properties shown in Examples 2 to 5 were obtained from the obtained mutant strains.
- L. helveticus CP3232 strain was obtained.
- L. helveticus CP3232 strain was anaerobically cultured on MRS agar medium at 37 ° C for 24 hours, and morphological and physiological properties of the obtained colonies were examined.
- sequence of 16S rRNA was determined and confirmed to have 99.9% homology with other Lactobacillus helveticus (type strain). Therefore, it was found that the obtained strain certainly belongs to L. helhelticus and is a novel strain.
- Example 2 Preparation of fermented milk 9.00% (w / w) reduced skim milk was sterilized at 95 ° C and cooled to 15 ° C and used as a milk medium.
- the milk medium was inoculated with fermented milk containing lactic acid bacteria at a rate of 5% and cultured at 37 ° C. for 24 hours. Furthermore, this was repeated and the obtained fermented milk was used as a starter. In the main culture, 3% of a starter was added to the milk medium and cultured at 32 ° C. or 37 ° C. for 24 hours.
- the pH and acidity of the fermented milk were measured. The acidity was measured using Hiranuma automatic titrator COMTITE-450 (Hiranuma Sangyo).
- L. helveticus CP3232 strain L. helveticus CP3264 strain (isolated from antihypertensive product), L. helveticus CM4 strain (accession number FERM BP-6060), L. helveticus CP1092 strain, L. helveticus CP1100 Strains, L. helveticus CP1081 strain and L. helveticus CPN4 strain (Japanese Patent Laid-Open No. 7-123977) were used.
- VPP equivalent ( ⁇ g / ml) IPP amount ( ⁇ g / ml) x 1.7 + VPP amount ( ⁇ g / ml)
- “acidity” represents the concentration of acid (lactic acid) contained in fermented milk. As shown in Table 1, in fermented milk obtained by fermentation of L. helveticus CP3232 strain, the amount of IPP peptide and VPP peptide relative to the lactic acid produced (that is, acidity) is 6.2 mg / g in terms of VPP, A high amount of peptide per acidity was shown. Fermented milk specific gravity was calculated as 1.02.
- Example 3 Measurement of free amino acids in fermented milk supernatant
- the fermented milk obtained in Example 2 was centrifuged at 10,000 g for 10 minutes, and the supernatant was appropriately diluted with distilled water, and then 0.2 ⁇ M membrane. It filtered with the filter and measured with the amino acid automatic analyzer (C-R7A / LC-10A) of a high performance liquid chromatography (HPLC, Shimadzu Corporation).
- the analysis conditions are as follows.
- FIG. 1A shows the results of the amount of each amino acid (nmol / ml) contained in the fermented milk supernatant obtained by fermenting each lactic acid bacterium at 32 ° C. for 24 hours
- B shows each lactic acid bacterium at 37 ° C.
- the result of the amino acid amount (nmol / ml) contained in the fermented milk supernatant obtained by fermenting for 24 hours is shown.
- 2A shows the total amount of free amino acids ( ⁇ mol / ml) contained in the fermented milk supernatant obtained by fermenting each lactic acid bacterium at 32 ° C. or 37 ° C.
- Example 4 Peptide content in fermented milk supernatant (OPA method) The amount of peptide in the fermented milk supernatant obtained in Example 2 was measured according to the method of Church et al. (J. Dairy Sci. 1983. 66: 1219-1227.). Briefly, 25 ml of 100 mM sodium tetraborate solution, 2.5 ml of 20% SDS, and 0.1 ml of 2-mercaptoethanol were mixed, and 1 ml of a solution of 4% by weight of o-phthalaldehyde dissolved in methanol was added to the final solution. The solution was adjusted to 50 ml with distilled water and used as an OPA reagent.
- Example 2 The fermented milk obtained in Example 2 was centrifuged at 10,000 g for 10 minutes, and the culture supernatant was appropriately diluted to obtain an analysis sample. 200 ⁇ l of OPA reagent and 10 ⁇ l of analysis sample were mixed and stirred sufficiently, then left at room temperature for 5 minutes, and absorption at 340 nm was measured. Bacttripton was used as a standard substance.
- L. helveticus CP3232 strain has high proteolytic activity and produces many peptides by fermentation. Specifically, peptides of 8.5 mg / ml or more were produced by fermentation for 24 hours, peptides of 11.1 mg / ml were produced by fermentation at 32 ° C., and peptides of 9.6 mg / ml were produced by fermentation at 37 ° C. (FIG. 3).
- Example 5 Quantification of functional peptide The fermented milk obtained in Example 2 was centrifuged at 10,000 g for 10 minutes, the supernatant was appropriately diluted with distilled water, and then filtered through a 0.2 ⁇ M membrane filter. Analyzed by LC / MS. LC / MS analysis was performed according to the method of Inoue et al. (J. Biosci. Bioeng., 2009, 108, 111-115.). That is, the analysis was performed using an RP-aqueous column (Nomura Kagaku) as a separation column in the LCMS-2010A system (Shimadzu Corporation). The content was calculated using a synthetic peptide as a standard substance.
- Synthetic peptides include ( 13 C 5 ) Val- ( 13 C 5 ) Pro-Pro, Ile- ( 13 C 5 ) Pro-Pro, Glu-Pro, Gln-Pro (Purchased from Scrum), Leu-Pro -Pro, Tyr-Pro, Val-Pro, Ile-Pro, Ala-Pro, Arg-Pro, Thr-Pro, Met-Pro, Gly-Pro (and purchased from Bachem) were used.
- L. helveticus CP3232 strain has high proteolytic activity and produces a functional peptide (XP + XPP) of 260 ⁇ g / ml or more in total in 24 hours of fermentation. It was. Particularly, fermentation at 32 ° C. produced functional peptides of 318 ⁇ mol / ml (FIG. 5A) and fermentation at 37 ° C. at 282 ⁇ mol / ml (FIG. 5B).
- Example 6 Preparation of fermented milk and measurement of peptide amount
- L. helveticus CP3232 strain as a lactic acid bacterium, L. helveticus CNCM I-3435 strain Patent Document 4
- L. Using helveticus FERM BP-5445 Patent Document 7
- L. helveticus CM4 Accession No. FERM BP-6060
- the results are shown in Table 2.
- the “acidity” represents the concentration of acid (lactic acid) contained in the fermented milk.
- the amount of IPP peptide and VPP peptide relative to the lactic acid produced is 7.0 mg / g in terms of VPP, A high amount of peptide per acidity was shown.
- Fermented milk specific gravity was calculated as 1.02.
- Example 7 Measurement of free amino acids in fermented milk supernatant Using the fermented milk obtained in Example 6, the free amino acids were measured in the same manner as in Example 3. The results are shown in FIGS.
- 6A shows the result of each amino acid amount (nmol / ml) contained in the fermented milk supernatant obtained by fermenting each lactic acid bacterium at 32 ° C. for 24 hours
- B shows each lactic acid bacterium at 37 ° C.
- the result of the amino acid amount (nmol / ml) contained in the fermented milk supernatant obtained by fermenting for 24 hours is shown.
- 7A shows the total amount of free amino acids ( ⁇ mol / ml) contained in the fermented milk supernatant obtained by fermenting each lactic acid bacterium at 32 ° C. or 37 ° C.
- Example 8 Amount of peptide in fermented milk supernatant (OPA method) The amount of peptide in the fermented milk supernatant obtained in Example 6 was measured in the same manner as in Example 4. The result is shown in FIG. From this result, it was shown that L. helveticus CP3232 strain has high proteolytic activity and produces many peptides by fermentation. Specifically, the peptide was produced at a rate of 8.5 mg / ml or more by fermentation for 24 hours, the peptide at 10.4 mg / ml by fermentation at 32 ° C., and 9.1 mg / ml by fermentation at 37 ° C. (FIG. 8).
- Example 9 Quantification of functional peptide The fermented milk obtained in Example 6 was analyzed by LC / MS in the same manner as in Example 5, and the amount of functional peptide was measured. The results are shown in FIGS. From the results shown in FIGS. 9A and 9B, it was found that the L. helveticus CP3232 strain has a high proteolytic activity and produces various functional peptides by fermentation for 24 hours. The L. helveticus CP323232 strain produced particularly large amounts of VPP, IPP, YP, QP and TP.
- the L. helveticus CP3232 strain has a high proteolytic activity and produces a functional peptide (XP + XPP) of 260 ⁇ g / ml or more in total in 24 hours of fermentation. It was.
- a functional peptide of 280 ⁇ mol / ml (FIG. 10A) was produced by fermentation at 32 ° C. (FIG. 10A) and 295 ⁇ mol / ml was produced by fermentation at 37 ° C. (FIG. 10B).
- Primer agccacttcctccgattacag (SEQ ID NO: 1) and gctattttagcagcgattcg (SEQ ID NO: 2).
- each lane is as follows.
- Lane 1 L. helveticus CP3232 strain
- Lane 2 L. helveticus CM4 strain
- Lane 3 L. helveticus CP3231 strain
- Lane 4 L. helveticus CP3264 strain
- Lane 5 L. helveticus CP1081 strain
- Lane 6 L. helveticus CP209 strain
- Lane 7 L. helveticus CP210 strain
- Lane 8 L. helveticus CP293 strain
- Lane 9 L. helveticus CP617 strain
- Lane 10 L. helveticus CP39 strain
- Lane 11 L. helveticus CP790 strain
- Lane 12 L. heveticus JCM1120 strain M: ⁇ phage Degradation product of DNA restriction enzyme HindIII.
- characteristic DNA fragments were observed in CM4 mutant L. helveticus CP3232 strain, CP3231 strain and parent CM4 strain (lanes 1 to 3), and other L. helveticus strains were This fragment was not observed.
- a DNA marker a restriction enzyme HindIII degradation product of ⁇ phage DNA was simultaneously electrophoresed, and the molecular weight of a characteristic DNA fragment was measured. As a result, it was about 2.2 kb.
- L. helveticus CP3232 strain, CP3231 strain, and parent strain CM4 strain are identified by selecting L. helveticus CP3232 strain by peptide amount analysis in fermented milk using OPA reagent as described in Examples 4 and 8. Is also possible. That is, when the value of the peptide amount in the fermented milk prepared according to Example 2 was measured with the OPA reagent, the L. helveticus CP3231 strain and the CM4 strain were 7.5 mg / ml and 4.5 mg / ml, respectively. L.helveticus CP3232 strain shows a high value of 11.1 mg / ml and can be easily identified.
- FIG. 12 shows the result of electrophoresis after gene amplification by PCR using primers.
- each lane is as follows: Lane 1: L. helveticus CP3232 strain Lane 2: L. helveticus CM4 strain Lane 3: L. helveticus CNCM I-3435 strain Lane 4: L. helveticus FERM BP-5445 strain M: ⁇ phage DNA restriction enzyme HindIII degradation product
- a lactic acid bacterium belonging to Lactobacillus helveticus having high proteolytic activity and excellent peptide production ability and / or amino acid production ability.
- the amino acids and / or peptides produced by this lactic acid bacterium have various functions.
- peptides such as IPP, VPP, and YP have a blood pressure lowering effect.
- fermented milk having a variety of amino acids and / or peptides having various functions at a high concentration and having a good flavor can be obtained. Therefore, the present invention is useful in fields such as medicine, food and drink, and health promotion.
- Sequence numbers 1 and 2 DNA (synthetic oligonucleotide)
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Abstract
Description
[1]以下の(a)~(d)のうち少なくとも1つの性質を有することを特徴とするラクトバチルス・ヘルベティカスに属する乳酸菌。
(a)獣乳を発酵させることにより遊離アミノ酸を25μmol/ml以上生成する
(b)獣乳を発酵させることによりペプチドを8.5mg/ml以上生成する
(c)獣乳を発酵させることによりXPペプチド及び/又はXPPペプチドを総量で260μg/ml以上生成する
(d)獣乳を30℃以上34℃以下で発酵させて得られる発酵乳の酸度当たりのIPPペプチド及びVPPペプチドの量がVPP換算量で6.0mg/g以上である
[2]遊離アミノ酸の15%以上が分岐鎖アミノ酸である、[1]に記載の乳酸菌。
[3]遊離アミノ酸がアラニン、リジン及びセリンから選択される少なくとも1種を含む、[1]又は[2]に記載の乳酸菌。
[4]YPペプチドを60μg/ml以上生成する、[1]~[3]のいずれかに記載の乳酸菌。
[5]ラクトバチルス・ヘルベティカスCM4株(受託番号 FERM BP-6060)の変異株である、[1]~[4]のいずれかに記載の乳酸菌。
[6]ラクトバチルス・ヘルベティカスCP3232株(受託番号 FERM BP-11271)又はその変異株である、[1]~[5]のいずれかに記載の乳酸菌。
[7]ラクトバチルス・ヘルベティカスCP3232株(受託番号 FERM BP-11271)。 That is, the present invention includes the following.
[1] A lactic acid bacterium belonging to Lactobacillus helveticus characterized by having at least one of the following properties (a) to (d):
(A) Fermented animal milk produces free amino acids of 25 μmol / ml or more (b) Fermented animal milk produces peptides of 8.5 mg / ml or more (c) XP peptide produced by fermenting animal milk And / or producing XPP peptide in a total amount of 260 μg / ml or more (d) The amount of IPP peptide and VPP peptide per acidity of fermented milk obtained by fermenting animal milk at 30 ° C. to 34 ° C. in terms of VPP [2] The lactic acid bacterium according to [1], wherein 6.0% / g or more [2] 15% or more of the free amino acids are branched chain amino acids.
[3] The lactic acid bacterium according to [1] or [2], wherein the free amino acid contains at least one selected from alanine, lysine and serine.
[4] The lactic acid bacterium according to any one of [1] to [3], wherein YP peptide is produced at 60 μg / ml or more.
[5] The lactic acid bacterium according to any one of [1] to [4], which is a mutant strain of Lactobacillus helveticus CM4 strain (Accession No. FERM BP-6060).
[6] The lactic acid bacterium according to any one of [1] to [5], which is a Lactobacillus helveticus CP3232 strain (Accession No. FERM BP-11271) or a mutant thereof.
[7] Lactobacillus helveticus CP3232 strain (Accession number FERM BP-11271).
[9]獣乳を発酵させることにより遊離アミノ酸を25μmol/ml以上生成する、[8]に記載の組成物。
[10]遊離アミノ酸の15%以上が分岐鎖アミノ酸である、[9]に記載の組成物。
[11]遊離アミノ酸がアラニン、リジン及びセリンから選択される少なくとも1種を含む、[9]又は[10]に記載の組成物。
[12]獣乳を発酵させることによりペプチドを8.5mg/ml以上生成する、[8]~[11]のいずれかに記載の組成物。
[13]獣乳を発酵させることによりXPペプチド及び/又はXPPペプチドを総量で260μg/ml以上生成する、[8]~[12]のいずれかに記載の組成物。
[14]獣乳を発酵させることによりYPペプチドを60μg/ml以上生成する、[8]~[13]のいずれかに記載の組成物。
[15]獣乳を30℃以上34℃以下で発酵させて得られる発酵乳の酸度当たりのIPPペプチド及びVPPペプチドの量が6.0 mg/g以上である、[8]~[14]のいずれかに記載の組成物。
[16]乳酸菌が[1]~[7]のいずれかに記載の乳酸菌である、[8]~[15]のいずれかに記載の組成物。 [8] A composition for producing amino acids and / or peptides from animal milk, comprising at least one lactic acid bacterium belonging to Lactobacillus helveticus.
[9] The composition according to [8], wherein free amino acids are produced at 25 μmol / ml or more by fermenting animal milk.
[10] The composition according to [9], wherein 15% or more of the free amino acids are branched chain amino acids.
[11] The composition according to [9] or [10], wherein the free amino acid comprises at least one selected from alanine, lysine and serine.
[12] The composition according to any one of [8] to [11], wherein the peptide is produced by fermenting animal milk to produce 8.5 mg / ml or more.
[13] The composition according to any one of [8] to [12], wherein XP milk and / or XPP peptide is produced in a total amount of 260 μg / ml or more by fermenting animal milk.
[14] The composition according to any one of [8] to [13], wherein YP peptide is produced at 60 μg / ml or more by fermenting animal milk.
[15] Any of [8] to [14], wherein the amount of IPP peptide and VPP peptide per acidity of fermented milk obtained by fermenting animal milk at 30 to 34 ° C. is 6.0 mg / g or more A composition according to 1.
[16] The composition according to any one of [8] to [15], wherein the lactic acid bacterium is the lactic acid bacterium according to any one of [1] to [7].
(a)25μmol/ml以上の遊離アミノ酸
(b)8.5mg/ml以上のペプチド
(c)総量で260μg/ml以上のXPペプチド及び/又はXPPペプチド
(d)6.0mg/g以上であるIPPペプチド及びVPPペプチドの酸度当たりのVPP換算量
[18]少なくとも1種のラクトバチルス・ヘルベティカスに属する乳酸菌を含有するものである、[17]に記載の発酵乳。
[19][1]~[7]のいずれかに記載の少なくとも1種の乳酸菌を含有するものである、[17]又は[18]に記載の発酵乳。
[20]遊離アミノ酸の15%以上が分岐鎖アミノ酸である、[17]~[19]のいずれかに記載の発酵乳。
[21]遊離アミノ酸がアラニン、リジン及びセリンから選択される少なくとも1種を含む、[17]~[20]のいずれかに記載の発酵乳。
[22]60μg/ml以上のYPペプチドを含む、[17]~[21]のいずれかに記載の発酵乳。
[23]発酵が30℃以上34℃以下の温度で行われる、[17]~[22]のいずれかに記載の発酵乳。
[24]血圧降下剤、脳機能改善剤、自律神経調節剤、副交感神経調節剤、交感神経調節剤、栄養補助剤、エネルギー補給剤、筋肉分解・損傷抑制剤、筋肉増強剤、疲労感の軽減剤、持久力の向上剤、風味改善剤、又はアルコール代謝剤として使用するための、[17]~[23]のいずれかに記載の発酵乳。
[25][1]~[7]のいずれかに記載の少なくとも1種の乳酸菌及び/又はその処理物、並びに/あるいは[17]~[24]のいずれかに記載の発酵乳及び/又はその処理物を含有することを特徴とする飲食品。 [17] Fermentation obtained by fermenting animal milk using lactic acid bacteria belonging to at least one Lactobacillus helveticus, comprising at least one of the following components (a) to (d): milk.
(A) 25 μmol / ml or more free amino acid (b) 8.5 mg / ml or more peptide (c) 260 μg / ml or more XP peptide and / or XPP peptide (d) 6.0 mg / g or more IPP peptide and VPP converted amount per acidity of VPP peptide [18] Fermented milk according to [17], which contains at least one lactic acid bacterium belonging to Lactobacillus helveticus.
[19] The fermented milk according to [17] or [18], which contains at least one lactic acid bacterium according to any one of [1] to [7].
[20] The fermented milk according to any one of [17] to [19], wherein 15% or more of the free amino acids are branched chain amino acids.
[21] The fermented milk according to any of [17] to [20], wherein the free amino acid comprises at least one selected from alanine, lysine and serine.
[22] The fermented milk according to any one of [17] to [21], comprising YP peptide of 60 μg / ml or more.
[23] The fermented milk according to any one of [17] to [22], wherein the fermentation is performed at a temperature of 30 ° C. or higher and 34 ° C. or lower.
[24] Blood pressure lowering agent, brain function improving agent, autonomic nerve regulator, parasympathetic nerve regulator, sympathetic nerve regulator, nutritional supplement, energy supplement, muscle degradation / damage inhibitor, muscle enhancer, fatigue reduction The fermented milk according to any one of [17] to [23], for use as an agent, endurance improver, flavor improver, or alcohol metabolite.
[25] At least one lactic acid bacterium according to any one of [1] to [7] and / or a processed product thereof and / or fermented milk according to any one of [17] to [24] and / or its A food or drink characterized by containing a processed product.
[27]アミノ酸が分岐鎖アミノ酸である、[26]に記載の方法。
[28]アミノ酸がアラニン、リジン及びセリンから選択される少なくとも1種を含む、[26]又は[27]に記載の方法。
[29]ペプチドがXPペプチド及びXPPペプチドからなる群より選択される少なくとも1種である、[26]~[28]のいずれかに記載の方法。
[30]発酵を30℃以上34℃以下の温度で行う、[26]~[29]のいずれかに記載の方法。 [26] Fermented animal milk or milk protein using at least one lactic acid bacterium according to any one of [1] to [7] or a composition according to any one of [8] to [16] A method for producing an amino acid and / or peptide, comprising collecting an amino acid and / or peptide from a fermented product obtained.
[27] The method according to [26], wherein the amino acid is a branched chain amino acid.
[28] The method according to [26] or [27], wherein the amino acid comprises at least one selected from alanine, lysine and serine.
[29] The method according to any one of [26] to [28], wherein the peptide is at least one selected from the group consisting of XP peptide and XPP peptide.
[30] The method according to any one of [26] to [29], wherein the fermentation is performed at a temperature of 30 ° C to 34 ° C.
(a)ラクトバチルス・ヘルベティカスCM4株(受託番号 FERM BP-6060)又はラクトバチルス・ヘルベティカスCP3232株(受託番号 FERM BP-11271)の変異株を調製する工程、及び
(b)該変異株から、以下の(a)~(d)のうち少なくとも1つの性質を有する菌株を選抜する工程:
(a)獣乳を発酵させることにより遊離アミノ酸を25μmol/ml以上生成する
(b)獣乳を発酵させることによりペプチドを8.5mg/ml以上生成する
(c)獣乳を発酵させることによりXPペプチド及び/又はXPPペプチドを総量で260μg/ml以上生成する
(d)獣乳を30℃以上34℃以下で発酵させて得られる発酵乳の酸度当たりのIPPペプチド及びVPPペプチドの量がVPP換算量で6.0mg/g以上である、
を含む方法。 [31] A method for obtaining a lactic acid bacterium belonging to Lactobacillus helveticus having proteolytic activity, the following steps:
(A) a step of preparing a mutant strain of Lactobacillus helveticus CM4 strain (Accession number FERM BP-6060) or Lactobacillus helveticus CP3232 strain (Accession number FERM BP-11271); and (b) from the mutant strain, The step of selecting a strain having at least one property of (a) to (d) of:
(A) Fermented animal milk produces free amino acids of 25 μmol / ml or more (b) Fermented animal milk produces peptides of 8.5 mg / ml or more (c) XP peptide produced by fermenting animal milk And / or producing XPP peptide in a total amount of 260 μg / ml or more (d) The amount of IPP peptide and VPP peptide per acidity of fermented milk obtained by fermenting animal milk at 30 ° C. to 34 ° C. in terms of VPP 6.0 mg / g or more,
Including methods.
(a)獣乳を発酵させることにより遊離アミノ酸を25μmol/ml以上、好ましくは30μmol/ml以上生成する
(b)獣乳を発酵させることによりペプチドを8.5mg/ml以上、好ましくは10mg/ml以上生成する
(c)獣乳を発酵させることによりXPペプチド及び/又はXPPペプチドを総量で、260μg/ml以上、好ましくは280μg/ml以上、さらに好ましくは300μg/ml以上生成する
(d)獣乳を30℃以上34℃以下で発酵させて得られる発酵乳の酸度当たりのIPPペプチド及びVPPペプチドの量がVPP換算量で6.0mg/g以上である。 A lactic acid bacterium belonging to Lactobacillus helveticus according to the present invention is a kind of lactic acid bacterium that produces lactic acid from saccharides by fermentation, and is also referred to herein as “the lactic acid bacterium of the present invention”. The lactic acid bacterium of the present invention is characterized by having high proteolytic activity and excellent amino acid-producing ability and / or functional peptide-producing ability. Specifically, it has at least one of the following properties (a) to (d):
(A) fermenting animal milk to produce free amino acids of 25 μmol / ml or more, preferably 30 μmol / ml or more (b) fermenting animal milk to produce peptides at 8.5 mg / ml or more, preferably 10 mg / ml or more (C) fermenting animal milk to produce XP peptide and / or XPP peptide in a total amount of 260 μg / ml or more, preferably 280 μg / ml or more, more preferably 300 μg / ml or more (d) The amount of IPP peptide and VPP peptide per acidity of fermented milk obtained by fermentation at 30 ° C. or more and 34 ° C. or less is 6.0 mg / g or more in terms of VPP.
(VPP換算量μg/ml)=IPP量(μg/ml)×1.7+VPP量(μg/ml) Regarding (d), the acidity (acid concentration in the fermented milk) can be measured by a known neutralization titration method, for example, using a known automatic titration apparatus. Moreover, IPP peptide and VPP peptide can be measured by the method described regarding (c). The amount of IPP peptide and VPP peptide per acidity of fermented milk obtained by fermenting animal milk at 30 ° C. to 34 ° C. is 5.5 mg / ml or more, preferably 6.0 mg / ml in terms of VPP. More than ml. In addition, the said amount is calculated as fermented milk specific gravity 1.02. The amounts of the IPP peptide and VPP peptide described in the present specification are VPP equivalent amounts based on the ACE inhibitory activity, and can be determined by the following formula:
(VPP conversion amount μg / ml) = IPP amount (μg / ml) × 1.7 + VPP amount (μg / ml)
なお、本発明の乳酸菌は、湿潤菌体であっても又は乾燥菌体であってもよい。 Moreover, the microbial cell of lactic acid bacteria and / or a processed material can be dried, and can be made into a powdery material (powder) or a granular material. Although it does not restrict | limit especially as a specific drying method, For example, spray drying, drum drying, vacuum drying, freeze-drying etc. are mentioned, These can be employ | adopted individually or in combination. In that case, you may add the excipient | filler normally used as needed.
The lactic acid bacterium of the present invention may be a wet cell or a dry cell.
(a)25μmol/ml以上、好ましくは30μmol/mlの遊離アミノ酸(そのうち15%以上が分岐鎖アミノ酸であることが好ましい)
(b)8.5mg/ml以上、好ましくは10mg/ml以上のペプチド
(c)総量で260μg/ml以上、好ましくは280μg/ml以上、より好ましくは300μg/ml以上のXPペプチド及び/又はXPPペプチド
(d)6.0mg/g以上であるIPPペプチド及びVPPペプチドの酸度当たりのVPP換算量。 By fermenting animal milk using the lactic acid bacteria or composition of the present invention, a fermented milk composition containing amino acids and / or peptides at a high concentration can be obtained. Accordingly, the present invention is obtained by fermenting animal milk using at least one lactic acid bacterium belonging to Lactobacillus helveticus, comprising at least one component of the following (a) to (d): Provide fermented milk with:
(A) 25 μmol / ml or more, preferably 30 μmol / ml free amino acids (of which 15% or more are preferably branched chain amino acids)
(B) Peptide of 8.5 mg / ml or more, preferably 10 mg / ml or more (c) XP peptide and / or XPP peptide (c) in a total amount of 260 μg / ml or more, preferably 280 μg / ml or more, more preferably 300 μg / ml or more d) VPP equivalent amount per acidity of IPP peptide and VPP peptide that is 6.0 mg / g or more.
L. helveticus CM4株(受託番号 FERM BP-6060)を育種し、得られた変異株の中から、実施例2~5に示す性質を示す新規なL. helveticus CP3232株を得た。 [Example 1] Identification of L. helveticus CP3232 strain L. helveticus CM4 strain (Accession No. FERM BP-6060) was bred and novel mutants having the properties shown in Examples 2 to 5 were obtained from the obtained mutant strains. L. helveticus CP3232 strain was obtained.
9.00%(w/w)還元脱脂粉乳を95℃達温殺菌し、15℃に冷却したものを乳培地として利用した。乳培地に、乳酸菌を含む発酵乳を5%の割合で接種し、37℃24時間培養を行った。さらに、これを繰り返し、得られた発酵乳をスターターとして用いた。本培養は、乳培地にスターターを3%添加し、32℃又は37℃で24時間培養を行った。発酵乳のpH及び酸度を測定した。酸度は、平沼自動滴定装置COMTITE-450(平沼産業)を用いて測定した。乳酸菌として、L. helveticus CP3232株と、比較用にL. helveticus CP3264株(抗高血圧製品より分離)、L. helveticus CM4株(受託番号 FERM BP-6060)、L. helveticus CP1092株、L. helveticus CP1100株、L. helveticus CP1081株及びL. helveticus CPN4株(特開平7-123977号公報)を使用した。 [Example 2] Preparation of fermented milk 9.00% (w / w) reduced skim milk was sterilized at 95 ° C and cooled to 15 ° C and used as a milk medium. The milk medium was inoculated with fermented milk containing lactic acid bacteria at a rate of 5% and cultured at 37 ° C. for 24 hours. Furthermore, this was repeated and the obtained fermented milk was used as a starter. In the main culture, 3% of a starter was added to the milk medium and cultured at 32 ° C. or 37 ° C. for 24 hours. The pH and acidity of the fermented milk were measured. The acidity was measured using Hiranuma automatic titrator COMTITE-450 (Hiranuma Sangyo). L. helveticus CP3232 strain, L. helveticus CP3264 strain (isolated from antihypertensive product), L. helveticus CM4 strain (accession number FERM BP-6060), L. helveticus CP1092 strain, L. helveticus CP1100 Strains, L. helveticus CP1081 strain and L. helveticus CPN4 strain (Japanese Patent Laid-Open No. 7-123977) were used.
VPP換算量(μg/ml)=IPP量(μg/ml)×1.7+VPP量(μg/ml) The results are shown in Table 1. As a result, since the ACE inhibitory activity per weight of IPP is 1.7 times that of VPP, the amount of IPP and the amount of VPP were expressed as VPP equivalents by the following formula:
VPP equivalent (μg / ml) = IPP amount (μg / ml) x 1.7 + VPP amount (μg / ml)
実施例2で得られた発酵乳を、10000gで10分間遠心分離し、上清を蒸留水で適当に希釈した後、0.2μMのメンブレンフィルターでろ過し、高速液体クロマトグラフィ(HPLC、島津製作所)のアミノ酸自動分析計(C-R7A/LC-10A)によって測定した。分析条件は以下の通りである。 [Example 3] Measurement of free amino acids in fermented milk supernatant The fermented milk obtained in Example 2 was centrifuged at 10,000 g for 10 minutes, and the supernatant was appropriately diluted with distilled water, and then 0.2 μM membrane. It filtered with the filter and measured with the amino acid automatic analyzer (C-R7A / LC-10A) of a high performance liquid chromatography (HPLC, Shimadzu Corporation). The analysis conditions are as follows.
アンモニアトラップ:Shim-pack ISC-30Li (50mmL x 4.0 mmI.D.)
カラム温度:38~58℃
反応温度:65℃
移動相:島津アミノ酸分析用移動相キットLi型
反応液:島津アミノ酸分析用反応液キットOPA試薬
流速:0.4ml/min。 Column: Shim-pack Amino-Li (100mmL x 6.0mmI.D.)
Ammonia trap: Shim-pack ISC-30Li (50mmL x 4.0mmI.D.)
Column temperature: 38-58 ° C
Reaction temperature: 65 ° C
Mobile phase: Mobile phase kit for Shimadzu amino acid analysis Li type Reaction solution: Reaction solution kit for Shimadzu amino acid analysis OPA reagent Flow rate: 0.4 ml / min.
実施例2で得られた発酵乳上清中のペプチド量をChurchら(J. Dairy Sci. 1983. 66:1219-1227.)の方法に準じて測定した。簡単に説明すると、100mM四ホウ酸ナトリウム溶液25ml、20%SDS 2.5ml、2-メルカプトエタノール0.1mlを混合し、これにo-フタルアルデヒドをメタノールに4重量%溶解した溶液1mlを加え、最終的に蒸留水で50mlに調製し、これをOPA試薬とした。実施例2で得られた発酵乳を10000gで10分間遠心分離し、培養上清を適当に希釈して分析サンプルとした。OPA試薬200μlと分析サンプル10μlを混合し、十分攪拌した後、室温で5分放置し、340nmの吸収を測定した。標準物質として、バクトトリプトンを用いた。 [Example 4] Peptide content in fermented milk supernatant (OPA method)
The amount of peptide in the fermented milk supernatant obtained in Example 2 was measured according to the method of Church et al. (J. Dairy Sci. 1983. 66: 1219-1227.). Briefly, 25 ml of 100 mM sodium tetraborate solution, 2.5 ml of 20% SDS, and 0.1 ml of 2-mercaptoethanol were mixed, and 1 ml of a solution of 4% by weight of o-phthalaldehyde dissolved in methanol was added to the final solution. The solution was adjusted to 50 ml with distilled water and used as an OPA reagent. The fermented milk obtained in Example 2 was centrifuged at 10,000 g for 10 minutes, and the culture supernatant was appropriately diluted to obtain an analysis sample. 200 μl of OPA reagent and 10 μl of analysis sample were mixed and stirred sufficiently, then left at room temperature for 5 minutes, and absorption at 340 nm was measured. Bacttripton was used as a standard substance.
実施例2で得られた発酵乳を、10000gで10分間遠心分離し、上清を蒸留水で適当に希釈した後、0.2μMのメンブレンフィルターでろ過し、LC/MSで分析した。LC/MS分析は、Inoueら(J. Biosci. Bioeng., 2009, 108, 111-115.)の方法に従い実施した。すなわち、LCMS-2010Aシステム(島津製作所)に、分離カラムとしてRP-aqueousカラム(野村科学)を用い分析を行った。合成ペプチドを標準物質として含有量を算出した。合成ペプチドは、(13C5)Val-(13C5)Pro-Pro、Ile-(13C5)Pro-Pro、Glu-Pro、Gln-Pro(以上、スクラム社より購入)、Leu-Pro-Pro, Tyr-Pro、Val-Pro、Ile-Pro、Ala-Pro, Arg-Pro、Thr-Pro、Met-Pro、Gly-Pro(以上、Bachem社より購入)を用いた。 [Example 5] Quantification of functional peptide The fermented milk obtained in Example 2 was centrifuged at 10,000 g for 10 minutes, the supernatant was appropriately diluted with distilled water, and then filtered through a 0.2 μM membrane filter. Analyzed by LC / MS. LC / MS analysis was performed according to the method of Inoue et al. (J. Biosci. Bioeng., 2009, 108, 111-115.). That is, the analysis was performed using an RP-aqueous column (Nomura Kagaku) as a separation column in the LCMS-2010A system (Shimadzu Corporation). The content was calculated using a synthetic peptide as a standard substance. Synthetic peptides include ( 13 C 5 ) Val- ( 13 C 5 ) Pro-Pro, Ile- ( 13 C 5 ) Pro-Pro, Glu-Pro, Gln-Pro (Purchased from Scrum), Leu-Pro -Pro, Tyr-Pro, Val-Pro, Ile-Pro, Ala-Pro, Arg-Pro, Thr-Pro, Met-Pro, Gly-Pro (and purchased from Bachem) were used.
実施例2と同様に、乳酸菌として、L. helveticus CP3232株と、比較用にL. helveticus CNCM I-3435株(特許文献4)、L. helveticus FERM BP-5445株(特許文献7)、及びL. helveticus CM4株(受託番号 FERM BP-6060)を使用して、培養後の発酵乳のpH及び酸度と、生成されたIPPペプチド及びVPPペプチドの量を測定した。 [Example 6] Preparation of fermented milk and measurement of peptide amount As in Example 2, L. helveticus CP3232 strain as a lactic acid bacterium, L. helveticus CNCM I-3435 strain (Patent Document 4), L. Using helveticus FERM BP-5445 (Patent Document 7) and L. helveticus CM4 (Accession No. FERM BP-6060), the pH and acidity of the fermented milk after culturing, and the IPP and VPP peptides produced The amount of was measured.
実施例6で得られた発酵乳を用いて、実施例3と同様に遊離アミノ酸について測定した。その結果を図6及び7に示す。 [Example 7] Measurement of free amino acids in fermented milk supernatant Using the fermented milk obtained in Example 6, the free amino acids were measured in the same manner as in Example 3. The results are shown in FIGS.
実施例6で得られた発酵乳上清中のペプチド量を、実施例4と同様に測定した。その結果を図8に示す。この結果から、L. helveticus CP3232株が高いタンパク質分解活性を有し、発酵により多くのペプチドを生成することが示された。具体的には、24時間の発酵でペプチドを8.5mg/ml以上生成し、32℃の発酵では10.4mg/ml、37℃の発酵では9.1mg/mlのペプチドを生成した(図8)。 [Example 8] Amount of peptide in fermented milk supernatant (OPA method)
The amount of peptide in the fermented milk supernatant obtained in Example 6 was measured in the same manner as in Example 4. The result is shown in FIG. From this result, it was shown that L. helveticus CP3232 strain has high proteolytic activity and produces many peptides by fermentation. Specifically, the peptide was produced at a rate of 8.5 mg / ml or more by fermentation for 24 hours, the peptide at 10.4 mg / ml by fermentation at 32 ° C., and 9.1 mg / ml by fermentation at 37 ° C. (FIG. 8).
実施例6で得られた発酵乳を、実施例5と同様にLC/MSで分析し、機能性ペプチド量を測定した。その結果を図9及び10に示す。図9のA及びBに示す結果から、L. helveticus CP3232株が高いタンパク質分解活性を有し、24時間の発酵で種々の機能性ペプチドを生成することがわかった。L. helveticus CP3232株は、特にVPP、IPP、YP、QP及びTPを多く生成した。 [Example 9] Quantification of functional peptide The fermented milk obtained in Example 6 was analyzed by LC / MS in the same manner as in Example 5, and the amount of functional peptide was measured. The results are shown in FIGS. From the results shown in FIGS. 9A and 9B, it was found that the L. helveticus CP3232 strain has a high proteolytic activity and produces various functional peptides by fermentation for 24 hours. The L. helveticus CP3232 strain produced particularly large amounts of VPP, IPP, YP, QP and TP.
実施例1において得られた乳酸菌L. helveticus CP3232株とその変異株は、実施例2~9に記載したような方法により測定することに加えて、ポリメラーゼ連鎖反応(PCR)法による識別を組み合わせることで、他の乳酸菌株と容易に識別が可能である。また、L. helveticus CP3232株の親株であるL. helveticus CM4株の変異株であるか否かも、PCR法により簡便に判定することができる。 [Reference Example 1] Identification method of L. helveticus CP3232 strain and mutants thereof Lactic acid bacteria L. helveticus CP3232 strain obtained in Example 1 and mutants thereof are measured by the methods described in Examples 2-9. In addition, it can be easily distinguished from other lactic acid strains by combining polymerase chain reaction (PCR) identification. Whether or not it is a mutant of the L. helveticus CM4 strain, which is the parent strain of the L. helveticus CP3232 strain, can also be easily determined by the PCR method.
agccacttcctccgattacag(配列番号1)、及び
gctattttagcagcgattcg(配列番号2)。 Primer:
agccacttcctccgattacag (SEQ ID NO: 1) and gctattttagcagcgattcg (SEQ ID NO: 2).
レーン2:L. helveticus CM4株
レーン3:L. helveticus CP3231株
レーン4:L. helveticus CP3264 株
レーン5:L. helveticus CP1081株
レーン6:L. helveticus CP209株
レーン7:L. helveticus CP210株
レーン8:L. helveticus CP293株
レーン9:L. helveticus CP617株
レーン10:L. helveticus CP39株
レーン11:L. helveticus CP790株
レーン12:L.helveticus JCM1120株
M:λファージDNA制限酵素HindIII分解物。 Lane 1: L. helveticus CP3232 strain Lane 2: L. helveticus CM4 strain Lane 3: L. helveticus CP3231 strain Lane 4: L. helveticus CP3264 strain Lane 5: L. helveticus CP1081 strain Lane 6: L. helveticus CP209 strain Lane 7 : L. helveticus CP210 strain Lane 8: L. helveticus CP293 strain Lane 9: L. helveticus CP617 strain Lane 10: L. helveticus CP39 strain Lane 11: L. helveticus CP790 strain Lane 12: L. heveticus JCM1120 strain M: λ phage Degradation product of DNA restriction enzyme HindIII.
参考例1と同様にして、実施例1において得られた乳酸菌L. helveticus CP3232株とその変異株を、ポリメラーゼ連鎖反応(PCR)法によって、他の乳酸菌株(L. helveticus CNCM I-3435株(特許文献4)及びL. helveticus FERM BP-5445株(特許文献7))と識別できるかどうか試験した。 [Reference Example 2] Identification method of L. helveticus CP3232 strain and mutants thereof In the same manner as in Reference Example 1, lactic acid bacteria L. helveticus CP3232 strain obtained in Example 1 and mutants thereof were subjected to polymerase chain reaction (PCR). It was tested whether it could be distinguished from other lactic acid strains (L. helveticus CNCM I-3435 (Patent Document 4) and L. helveticus FERM BP-5445 (Patent Document 7)) by the method.
レーン1:L. helveticus CP3232株
レーン2:L. helveticus CM4株
レーン3:L. helveticus CNCM I-3435株
レーン4:L. helveticus FERM BP-5445株
M:λファージDNA制限酵素HindIII分解物。 FIG. 12 shows the result of electrophoresis after gene amplification by PCR using primers. In FIG. 12, each lane is as follows:
Lane 1: L. helveticus CP3232 strain Lane 2: L. helveticus CM4 strain Lane 3: L. helveticus CNCM I-3435 strain Lane 4: L. helveticus FERM BP-5445 strain M: λ phage DNA restriction enzyme HindIII degradation product
受託番号FERM BP-6060(Lactobacillus Helveticus(ラクトバチルス・ヘルベチカス)CM4株、平成9年(1997年)8月15日寄託) Accession number FERM BP-11271 (Lactobacillus Helveticus CP3232 strain, deposited on August 4, 2010)
Accession number FERM BP-6060 (Lactobacillus Helveticus CM4 strain, deposited on August 15, 1997)
Claims (26)
- 以下の(a)~(d)のうち少なくとも1つの性質を有することを特徴とするラクトバチルス・ヘルベティカスに属する乳酸菌。
(a)獣乳を発酵させることにより遊離アミノ酸を25μmol/ml以上生成する
(b)獣乳を発酵させることによりペプチドを8.5mg/ml以上生成する
(c)獣乳を発酵させることによりXPペプチド及び/又はXPPペプチドを総量で260μg/ml以上生成する
(d)獣乳を30℃以上34℃以下で発酵させて得られる発酵乳の酸度当たりのIPPペプチド及びVPPペプチドの量がVPP換算量で6.0 mg/g以上である Lactic acid bacteria belonging to Lactobacillus helveticus characterized by having at least one of the following properties (a) to (d):
(A) Fermented animal milk produces free amino acids of 25 μmol / ml or more (b) Fermented animal milk produces peptides of 8.5 mg / ml or more (c) XP peptide produced by fermenting animal milk And / or producing XPP peptide in a total amount of 260 μg / ml or more (d) The amount of IPP peptide and VPP peptide per acidity of fermented milk obtained by fermenting animal milk at 30 ° C. to 34 ° C. in terms of VPP 6.0 mg / g or more - 遊離アミノ酸の15%以上が分岐鎖アミノ酸である、請求項1に記載の乳酸菌。 The lactic acid bacterium according to claim 1, wherein 15% or more of the free amino acids are branched chain amino acids.
- YPペプチドを60μg/ml以上生成する、請求項1又は2に記載の乳酸菌。 The lactic acid bacterium according to claim 1 or 2, which produces 60 μg / ml or more of YP peptide.
- ラクトバチルス・ヘルベティカスCM4株(受託番号 FERM BP-6060)の変異株である、請求項1~3のいずれか1項に記載の乳酸菌。 The lactic acid bacterium according to any one of claims 1 to 3, which is a mutant strain of Lactobacillus helveticus CM4 strain (Accession No. FERM BP-6060).
- ラクトバチルス・ヘルベティカスCP3232株(受託番号 FERM BP-11271)又はその変異株である、請求項1~4のいずれか1項に記載の乳酸菌。 The lactic acid bacterium according to any one of claims 1 to 4, which is Lactobacillus helveticus CP3232 strain (Accession number FERM BP-11271) or a mutant thereof.
- ラクトバチルス・ヘルベティカスCP3232株(受託番号 FERM BP-11271)。 Lactobacillus helveticus CP3232 strain (Accession number “FERM” BP-11271).
- 少なくとも1種のラクトバチルス・ヘルベティカスに属する乳酸菌を含有することを特徴とする、獣乳からアミノ酸及び/又はペプチドを生成するための組成物。 A composition for producing amino acids and / or peptides from animal milk, characterized by comprising at least one lactic acid bacterium belonging to Lactobacillus helveticus.
- 獣乳を発酵させることにより遊離アミノ酸を25μmol/ml以上生成する、請求項7に記載の組成物。 The composition according to claim 7, wherein free amino acids are produced at a rate of 25 µmol / ml or more by fermenting animal milk.
- 遊離アミノ酸の15%以上が分岐鎖アミノ酸である、請求項8に記載の組成物。 The composition according to claim 8, wherein 15% or more of the free amino acids are branched chain amino acids.
- 獣乳を発酵させることによりペプチドを8.5mg/ml以上生成する、請求項7~9のいずれか1項に記載の組成物。 The composition according to any one of claims 7 to 9, wherein the peptide is produced by fermenting animal milk to produce 8.5 mg / ml or more.
- 獣乳を発酵させることによりXPペプチド及び/又はXPPペプチドを総量で260μg/ml以上生成する、請求項7~10のいずれか1項に記載の組成物。 The composition according to any one of claims 7 to 10, wherein XP peptide and / or XPP peptide is produced in a total amount of 260 µg / ml or more by fermenting animal milk.
- 獣乳を発酵させることによりYPペプチドを60μg/ml以上生成する、請求項7~11のいずれか1項に記載の組成物。 The composition according to any one of claims 7 to 11, wherein the YP peptide is produced at 60 µg / ml or more by fermenting animal milk.
- 獣乳を30℃以上34℃以下で発酵させて得られる発酵乳の酸度当たりのIPPペプチド及びVPPペプチドの量がVPP換算量で6.0 mg/g以上である、請求項7~12のいずれか1項に記載の組成物。 The amount of IPP peptide and VPP peptide per acidity of fermented milk obtained by fermenting animal milk at 30 ° C to 34 ° C is 6.0 mg / g or more in terms of VPP, any one of claims 7-12 The composition according to item.
- 乳酸菌が請求項1~6のいずれか1項に記載の乳酸菌である、請求項7~13のいずれか1項に記載の組成物。 The composition according to any one of claims 7 to 13, wherein the lactic acid bacterium is the lactic acid bacterium according to any one of claims 1 to 6.
- 獣乳を少なくとも1種のラクトバチルス・ヘルベティカスに属する乳酸菌を用いて発酵させることにより得られ、以下の(a)~(d)のうち少なくとも1つの成分を含むことを特徴とする発酵乳。
(a)25μmol/ml以上の遊離アミノ酸
(b)8.5mg/ml以上のペプチド
(c)総量で260μg/ml以上のXPペプチド及び/又はXPPペプチド
(d)6.0mg/g以上であるIPPペプチド及びVPPペプチドの酸度当たりのVPP換算量 A fermented milk obtained by fermenting animal milk using at least one lactic acid bacterium belonging to Lactobacillus helveticus, comprising at least one of the following components (a) to (d):
(A) 25 μmol / ml or more free amino acid (b) 8.5 mg / ml or more peptide (c) 260 μg / ml or more XP peptide and / or XPP peptide (d) 6.0 mg / g or more IPP peptide and VPP equivalent per acidity of VPP peptide - 少なくとも1種のラクトバチルス・ヘルベティカスに属する乳酸菌を含有するものである、請求項15に記載の発酵乳。 The fermented milk according to claim 15, which contains at least one lactic acid bacterium belonging to Lactobacillus helveticus.
- 請求項1~6のいずれか1項に記載の少なくとも1種の乳酸菌を含有するものである、請求項15又は16に記載の発酵乳。 The fermented milk according to claim 15 or 16, which contains at least one lactic acid bacterium according to any one of claims 1 to 6.
- 遊離アミノ酸の15%以上が分岐鎖アミノ酸である、請求項15~17のいずれか1項に記載の発酵乳。 The fermented milk according to any one of claims 15 to 17, wherein 15% or more of the free amino acids are branched chain amino acids.
- 60μg/ml以上のYPペプチドを含む、請求項15~18のいずれか1項に記載の発酵乳。 The fermented milk according to any one of claims 15 to 18, comprising 60 μg / ml or more of YP peptide.
- 発酵が30℃以上34℃以下の温度で行われる、請求項15~19のいずれか1項に記載の発酵乳。 The fermented milk according to any one of claims 15 to 19, wherein the fermentation is performed at a temperature of 30 ° C to 34 ° C.
- 血圧降下剤、脳機能改善剤、自律神経調節剤、副交感神経調節剤、交感神経調節剤、栄養補助剤、エネルギー補給剤、筋肉分解・損傷抑制剤、筋肉増強剤、疲労感の軽減剤、持久力の向上剤、風味改善剤、又はアルコール代謝剤として使用するための、請求項15~20のいずれか1項に記載の発酵乳。 Antihypertensive agent, brain function improving agent, autonomic nerve regulator, parasympathetic nerve regulator, sympathetic nerve regulator, nutritional supplement, energy supplement, muscle degradation / damage inhibitor, muscle strengthening agent, fatigue reduction agent, endurance The fermented milk according to any one of claims 15 to 20, for use as a power improver, a flavor improver, or an alcohol metabolite.
- 請求項1~6のいずれか1項に記載の少なくとも1種の乳酸菌及び/又はその処理物、並びに/あるいは請求項15~21のいずれか1項に記載の発酵乳及び/又はその処理物を含有することを特徴とする飲食品。 The at least one lactic acid bacterium and / or processed product thereof according to any one of claims 1 to 6, and / or the fermented milk and / or processed product thereof according to any one of claims 15 to 21. A food or drink characterized by containing.
- 請求項1~6のいずれか1項に記載の少なくとも1種の乳酸菌又は請求項7~14のいずれか1項に記載の組成物を用いて獣乳又は乳タンパク質を発酵させ、得られる発酵物からアミノ酸及び/又はペプチドを採取することを特徴とするアミノ酸及び/又はペプチドの製造方法。 A fermented product obtained by fermenting animal milk or milk protein using at least one lactic acid bacterium according to any one of claims 1 to 6 or the composition according to any one of claims 7 to 14. A method for producing an amino acid and / or peptide comprising collecting an amino acid and / or peptide from
- アミノ酸が分岐鎖アミノ酸である、請求項23に記載の方法。 The method according to claim 23, wherein the amino acid is a branched chain amino acid.
- ペプチドがXPペプチド及び/又はXPPペプチドからなる群より選択される少なくとも1種である、請求項23又は24に記載の方法。 The method according to claim 23 or 24, wherein the peptide is at least one selected from the group consisting of XP peptides and / or XPP peptides.
- 発酵を30℃以上34℃以下の温度で行う、請求項23~25のいずれか1項に記載の方法。 The method according to any one of claims 23 to 25, wherein the fermentation is performed at a temperature of 30 ° C to 34 ° C.
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AU2011327288A AU2011327288B2 (en) | 2010-11-09 | 2011-11-08 | Lactobacillus helveticus having high proteolysis activity |
JP2012542934A JP5888701B2 (en) | 2010-11-09 | 2011-11-08 | Lactobacillus helveticus having high proteolytic activity |
CN201180054138.4A CN103221531B (en) | 2010-11-09 | 2011-11-08 | Lactobacillus helveticus with high protein hydrolysing activity |
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CN (1) | CN103221531B (en) |
AU (1) | AU2011327288B2 (en) |
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JP2017205039A (en) * | 2016-05-17 | 2017-11-24 | 小川香料株式会社 | Lactic acid bacterium survival improver |
WO2019124355A1 (en) * | 2017-12-18 | 2019-06-27 | 株式会社明治 | Muscle-synthesis-promoting fermented milk |
JPWO2018181455A1 (en) * | 2017-03-29 | 2020-02-06 | 株式会社明治 | Lactic acid bacteria starter and method for producing fermented milk |
WO2020085179A1 (en) * | 2018-10-26 | 2020-04-30 | アサヒグループホールディングス株式会社 | Anti-obesity agent, pollakiuria improving agent, and autonomic nervous activity regulator |
US10780127B2 (en) | 2016-06-23 | 2020-09-22 | National University Corporation Tottori University | Method for producing fermented milk having high angiotensin converting enzyme inhibitory activity and method for producing physiologically active peptide |
JP2020171321A (en) * | 2015-08-26 | 2020-10-22 | キリンビバレッジ株式会社 | Uht sterilized milk-containing beverage excellent in milk feeling |
EP3978075A4 (en) * | 2019-06-03 | 2023-07-12 | Asahi Group Holdings, Ltd. | Walking ability improver |
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CN107699524A (en) * | 2017-11-08 | 2018-02-16 | 苏州健世星生物科技有限公司 | A kind of preparation method of active black saccharolactic acid bacterium |
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CN109517763B (en) * | 2018-12-27 | 2022-03-22 | 内蒙古农业大学 | Lactobacillus helveticus H11 and application thereof |
JP7369992B2 (en) * | 2019-05-13 | 2023-10-27 | 株式会社明治 | Fermented milk for improving autonomic nervous function |
CN112029784A (en) * | 2020-09-16 | 2020-12-04 | 内蒙古农业大学 | Gene related to proteolytic ability and screening method of lactobacillus helveticus with high proteolytic ability based on gene |
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JP2017205039A (en) * | 2016-05-17 | 2017-11-24 | 小川香料株式会社 | Lactic acid bacterium survival improver |
US10780127B2 (en) | 2016-06-23 | 2020-09-22 | National University Corporation Tottori University | Method for producing fermented milk having high angiotensin converting enzyme inhibitory activity and method for producing physiologically active peptide |
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Also Published As
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CN103221531B (en) | 2018-03-16 |
TWI551684B (en) | 2016-10-01 |
AU2011327288B2 (en) | 2015-05-07 |
JPWO2012063826A1 (en) | 2014-05-12 |
AU2011327288A1 (en) | 2013-05-02 |
JP5888701B2 (en) | 2016-03-22 |
TW201305331A (en) | 2013-02-01 |
MY160992A (en) | 2017-03-31 |
CN103221531A (en) | 2013-07-24 |
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