JP2019517810A - Bacillus licheniformis NY1505 strain producing a large amount of α-glucosidase inhibitor - Google Patents
Bacillus licheniformis NY1505 strain producing a large amount of α-glucosidase inhibitor Download PDFInfo
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- JP2019517810A JP2019517810A JP2018565720A JP2018565720A JP2019517810A JP 2019517810 A JP2019517810 A JP 2019517810A JP 2018565720 A JP2018565720 A JP 2018565720A JP 2018565720 A JP2018565720 A JP 2018565720A JP 2019517810 A JP2019517810 A JP 2019517810A
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- bacillus licheniformis
- glucosidase inhibitor
- glucosidase
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- C12N1/20—Bacteria; Culture media therefor
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- 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
- C12R2001/07—Bacillus
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Abstract
本発明は、α−グルコシダーゼ阻害剤を高生産するバチルス・リケニフォルミスＮＹ１５０５菌株（受託番号ＫＣＴＣ１３０２１ＢＰ）を提供する。本発明によるバチルス・リケニフォルミスＮＹ１５０５菌株は、嫌気性条件でも生息が可能な新菌株であって、腸内でα−グルコシダーゼ阻害剤を生産して供給するので、有効濃度を一定に保持して、優れた体重減量及び血糖降下の効果を示し、腸内に固着せず、一時的に生息する特性を示して、必要に応じて投与された菌株または菌株が生産したα−グルコシダーゼ阻害剤は、排出が可能であって、安全に使用することができる。また、α−グルコシダーゼ阻害剤の生成のための別途の発酵コスト及び加工費が不要であって、生産コストを節減し、発酵臭などの問題が発生せず、多様な形態の食品に適用が可能である。【選択図】図１The present invention provides Bacillus licheniformis NY1505 strain (Accession No. KCTC13021BP) which highly produces an α-glucosidase inhibitor. The Bacillus licheniformis NY1505 strain according to the present invention is a new strain which can be inhabited even under anaerobic conditions, and since it produces and supplies an α-glucosidase inhibitor in the intestine, its effective concentration can be maintained constant to be excellent. Show the effects of weight loss and hypoglycemia, do not stick in the intestines, show temporary inhabiting characteristics, and the α-glucosidase inhibitors produced by the strain or strains administered as needed are excreted It is possible and safe to use. In addition, there is no need for separate fermentation and processing costs for the production of an α-glucosidase inhibitor, which reduces the production cost, does not cause problems such as fermentation odor, and can be applied to various forms of food It is. [Selected figure] Figure 1
Description
本発明は、α−グルコシダーゼ阻害剤を多量生産する新菌株であるバチルス・リケニフォルミスＮＹ１５０５菌株（Ｂａｃｉｌｌｕｓ ｌｉｃｈｅｎｉｆｏｒｍｉｓ ＮＹ１５０５）に関する。 The present invention relates to Bacillus licheniformis NY1505 strain (Bacillus licheniformis NY1505), which is a new strain that produces a large amount of an α-glucosidase inhibitor.
α−グルコシダーゼ阻害剤（α−ｇｌｕｃｏｓｉｄａｓｅ ｉｎｈｉｂｉｔｏｒｓ）は、一部の植物や微生物に分布し、オリゴ糖の単糖類への分解を抑制する作用を行う物質である。 An alpha-glucosidase inhibitor (alpha-glucosidase inhibitors) is a substance which distributes in a part of plants and microorganisms, and which has an action which controls degradation to a monosaccharide of an oligosaccharide.
α−グルコシダーゼ活性の阻害は、腸内で糖類の円滑な吸収を阻害することにより、食後血糖上昇抑制はもとより、肥満治療のような付随的な効果が期待されるので、α−グルコシダーゼ阻害剤を経済的に量産するための必要性は次第に高まりつつある。 Since inhibition of α-glucosidase activity inhibits smooth absorption of saccharides in the intestine, suppression of postprandial blood glucose elevation as well as concomitant effects such as obesity treatment are expected, so α-glucosidase inhibitors The need for economical mass production is increasing.
植物由来のα−グルコシダーゼ阻害剤としては、桑の葉に含有された１−デオキシノジリマイシン（１−ｄｅｏｘｙｎｏｊｉｒｉｍｙｃｉｎ）のようなアザ糖（ａｚａ ｓｕｇａｒ）類、大豆に含有されたゲニステイン（ｇｅｎｉｓｔｅｉｎ）、ダイゼイン（ｄａｉｄｚｅｉｎ）のようなイソフラボン（ｉｓｏｆｌａｖｏｎｅ）、一部のフラボン配糖体（ｆｌａｖｏｎｅ ｇｌｙｃｏｓｉｄｅ）などが知られており、微生物由来のα−グルコシダーゼ阻害剤としては、アクチノプラネス属（Ａｃｔｉｎｏｐｌａｎｅｓ）菌株由来の類似オリゴ糖（ｐｓｅｕｄｏｏｌｉｇｏｓａｃｃｈａｒｉｄｅ）、ストレプトミセス属（Ｓｔｒｅｐｔｏｍｙｃｅｓ）またはバチルス属（Ｂａｃｉｌｌｕｓ）などの微生物が生産する１−デオキシノジリマイシン、トリス塩（ｔｒｉｓ ｂａｓｅ）などが知られており、医薬品としては、アカルボース（ａｃａｒｂｏｓｅ）、ボグリボース（ｖｏｇｌｉｂｏｓｅ）のようなα−グルコシダーゼ阻害剤が既に糖尿病治療剤として販売されている。 Examples of plant-derived α-glucosidase inhibitors include aza sugars such as 1-deoxynojirimycin contained in persimmon leaves, genistein contained in soybeans, daidzein There are known isoflavones such as (daidzein), some flavone glycosides, and the like, and as a microorganism-derived α-glucosidase inhibitor, similarities derived from Actinoplanes strains are known. 1-deoxynojirimycin produced by microorganisms such as oligosaccharides (pseudooligosaccharide), Streptomyces or Bacillus (Bacillus), And the like squirrel salt (tris base) are known, as pharmaceuticals, acarbose (acarbose), alpha-glucosidase inhibitors such as voglibose (voglibose) is already marketed as an antidiabetic agent.
最近、血糖降下に効果があるα−グルコシダーゼ阻害剤を食品として摂取するために、食用可能な天産物についての研究が活発に進められている。食品として使われる天産物由来のα−グルコシダーゼ阻害剤は、植物の場合、桑の葉、微生物の場合、一部の納豆を代表的な例として挙げられる。これらの１次加工品または抽出物は、量産されているが、共通してにおい、色沢のような嗜好性を落とす因子を有しているので、製品の多様化に制限がある。また、これらは、植物または微生物が生産した二次代謝産物を利用する場合なので、一日に数回一定量を服用して初めて、所期の目的を果たすことができるという短所がある。 Recently, research is being actively conducted on edible natural products in order to ingest an α-glucosidase inhibitor effective for hypoglycemia as a food. Natural product-derived α-glucosidase inhibitors used as food can be mentioned as representative examples of bamboo leaves in the case of plants and natto in the case of microorganisms. Although these primary processed products or extracts are mass-produced, they have factors in common that they lose taste such as odor and color so that there is a limit to product diversification. In addition, since they use secondary metabolites produced by plants or microorganisms, they have the disadvantage that they can achieve their intended purpose only after taking a fixed amount several times a day.
一方、乳酸菌のような腸内細菌は、腸内で生息しながら増殖する特性を有している。したがって、α−グルコシダーゼ阻害剤のような二次代謝産物を生産する腸内細菌は、腸内で増殖しながら切れ目なく腸内環境にα−グルコシダーゼ阻害剤を生産して供給すると予想される。しかし、従来に知られたバチルス・サブチリス（Ｂａｃｉｌｌｕｓ ｓｕｂｔｉｌｉｓ）のような一部の納豆菌は、α−グルコシダーゼ阻害剤を生産すると知られているが、バチルス・サブチリスは、好気性菌で腸内で生息しにくいために、バチルス・サブチリスの増殖でα−グルコシダーゼ阻害剤を腸内で供給されることは難しく、納豆の摂取を通じてα−グルコシダーゼ阻害剤を供給されるためには、多量摂取しなければならないという問題点がある。 On the other hand, intestinal bacteria such as lactic acid bacteria have the property of proliferating while in the intestines. Thus, enterobacteria that produce secondary metabolites such as alpha-glucosidase inhibitors are expected to proliferate in the gut and produce and supply alpha-glucosidase inhibitors seamlessly to the gut environment. However, some Bacillus natto bacteria, such as Bacillus subtilis, which are known to date, are known to produce α-glucosidase inhibitors, but Bacillus subtilis is an aerobic bacterium, which is an intestinal bacterium. Because it is difficult to inhabit, it is difficult to supply the α-glucosidase inhibitor in the intestines by growth of Bacillus subtilis, and in order to be supplied with the α-glucosidase inhibitor through the intake of natto, it must be ingested in large quantities. There is a problem that it is impossible.
したがって、腸内で生息が可能であり、α−グルコシダーゼ阻害剤を多量生成することができて、体重減量と血糖降下などのための目的として効果的に活用可能な新たな菌株についての研究及び開発が必要である。 Therefore, research and development of new strains that can be inhabited in the intestine, can produce a large amount of α-glucosidase inhibitors, and can be effectively used as weight loss and hypoglycemic purposes, etc. is necessary.
本発明者らは、α−グルコシダーゼ阻害活性が強い腸内微生物を選抜するために鋭意研究した結果、α−グルコシダーゼ阻害活性を示す微生物のうちから通性嫌気性であり、胞子を形成し、腸内で増殖が可能なＧＲＡＳ菌としてα−グルコシダーゼ阻害剤を多量で生産する新規なバチルス・リケニフォルミスＮＹ１５０５菌株を分離・同定し、前記微生物の発酵物または胞子を含んだ栄養細胞は、体重減量と血糖降下とを目的として食品、医薬品、飼料などに有用に使われうるということを確認した。 As a result of intensive studies to select enteric microorganisms having strong α-glucosidase inhibitory activity, the present inventors are facultatively anaerobic from the microorganisms exhibiting α-glucosidase inhibitory activity, form spores, and entero We isolated and identified a novel Bacillus licheniformis NY1505 strain that produces a large amount of α-glucosidase inhibitor as a GRAS strain capable of growing in the inside, vegetative cells containing the fermented product of the microorganism or spores, weight loss and blood sugar We confirmed that it could be usefully used for food, medicine, feed, etc. for the purpose of descent.
これにより、本発明では、α−グルコシダーゼ阻害剤を多量生産する新菌株であるバチルス・リケニフォルミスＮＹ１５０５菌株に関する技術内容を提供することをその目的とする。 Accordingly, it is an object of the present invention to provide technical contents related to Bacillus licheniformis NY1505 strain, which is a new strain that produces a large amount of an α-glucosidase inhibitor.
前記のような技術的課題を果たすために、本発明は、α−グルコシダーゼ阻害剤を高生産するバチルス・リケニフォルミスＮＹ１５０５菌株（受託番号ＫＣＴＣ１３０２１ＢＰ）を提供する。 In order to achieve the technical problems as described above, the present invention provides Bacillus licheniformis NY1505 strain (Accession No. KCTC13021BP) which highly produces an α-glucosidase inhibitor.
また、前記菌株は、配列番号１の１６ｓ ＲＮＡを含むことを特徴とする。 Also, the strain is characterized in that it comprises 16s RNA of SEQ ID NO: 1.
また、前記菌株は、嫌気性であるか、または、好気性であり得る。 Also, the strain may be anaerobic or aerobic.
また、前記菌株は、胞子を形成し、前記菌株が投与された後、生物体から２週以内に***されうる。 Also, the strain may form spores and be excreted from the organism within two weeks after the strain is administered.
また、前記菌株は、動物の腸内でα−グルコシダーゼ阻害剤を生産し、腸内で生産されたα−グルコシダーゼ阻害剤は、前記菌株が投与された後、生物体から２週以内に***されうる。 In addition, the strain produces an α-glucosidase inhibitor in the intestine of the animal, and the α-glucosidase inhibitor produced in the intestine is excreted from the organism within two weeks after the strain is administered. sell.
また、本発明は、前記菌株を含む食品組成物を提供する。 The present invention also provides a food composition comprising the strain.
また、前記食品組成物には、前記菌株が胞子の形態で含まれ、１ｋｇ当たり１０６〜１０１０個の胞子で含まれうる。 Also, the food composition may include the strain in the form of spores, and may contain 10 6 to 10 10 spores per kg.
また、前記食品組成物は、前記菌株の発酵物をさらに含み、前記発酵物は、大豆発酵物であり得る。 In addition, the food composition may further include a fermented product of the strain, and the fermented product may be a fermented soybean.
本発明によるバチルス・リケニフォルミスＮＹ１５０５菌株は、嫌気性条件でも生息が可能な新菌株であって、腸内でα−グルコシダーゼ阻害剤を生産して供給するので、有効濃度を一定に保持して、優れた体重減量及び血糖降下の効果を示し、腸内に固着せず、一時的に生息する特性を示して、必要に応じて投与された菌株または菌株が生産したα−グルコシダーゼ阻害剤は、排出が可能であって、安全に使用することができる。 The Bacillus licheniformis NY1505 strain according to the present invention is a new strain which can be inhabited even under anaerobic conditions, and since it produces and supplies an α-glucosidase inhibitor in the intestine, its effective concentration can be maintained constant to be excellent. Show the effects of weight loss and hypoglycemia, do not stick in the intestines, show temporary inhabiting characteristics, and the α-glucosidase inhibitors produced by the strain or strains administered as needed are excreted It is possible and safe to use.
また、α−グルコシダーゼ阻害剤の生成のための別途の発酵コスト及び加工費が不要であって、生産コストを節減し、発酵臭などの問題が発生せず、多様な形態の食品に適用が可能である。 In addition, there is no need for separate fermentation and processing costs for the production of an α-glucosidase inhibitor, which reduces the production cost, does not cause problems such as fermentation odor, and can be applied to various forms of food It is.
以下、本発明を詳しく説明する。 Hereinafter, the present invention will be described in detail.
本発明は、α−グルコシダーゼ阻害剤を高生産するバチルス・リケニフォルミスＮＹ１５０５菌株（受託番号ＫＣＴＣ１３０２１ＢＰ）を提供する。 The present invention provides Bacillus licheniformis NY1505 strain (Accession No. KCTC13021BP) which highly produces an α-glucosidase inhibitor.
前記菌株は、稲わら及び乾草を試料として耐熱性胞子を形成する菌を分離し、生体内で生育が可能であり、α−グルコシダーゼ阻害剤を高生産する菌株を選別することで得られる。 The said strain isolates the microbe which forms a heat-resistant spore by making a rice straw and a hay into a sample, and it can be grown in in vivo, and it is obtained by selecting the strain which carries out high production of the alpha-glucosidase inhibitor.
前記菌株は、下記の配列番号１の１６ｓ ＲＮＡを含むことを特徴とする。 The strain is characterized by containing 16s RNA of SEQ ID NO: 1 below.
配列番号１：
ＡＧＧＧＣＴＴＣＣＣＣＴＴＣＧＧＧＧＧＣＡＧＡＧＴＧＡＣＡＧＧＴＧＧＴＧＣＡＴＧＧＴＴＧＴＣＧＴＣＡＧＣＴＣＧＴＧＴＣＧＴＧＡＧＡＴＧＴＴＧＧＧＴＴＡＡＧＴＣＣＣＧＣＡＡＣＧＡＧＣＧＣＡＡＣＣＣＴＴＧＡＴＣＴＴＡＧＴＴＧＣＣＡＧＣＡＴＴＣＡＧＴＴＧＧＧＣＡＣＴＣＴＡＡＧＧＴＧＡＣＴＧＣＣＧＧＴＧＡＣＡＡＡＣＣＧＧＡＧＧＡＡＧＧＴＧＧＧＧＡＴＧＡＣＧＴＣＡＡＡＴＣＡＴＣＡＴＧＣＣＣＣＴＴＡＴＧＡＣＣＴＧＧＧＣＴＡＣＡＣＡＣＧＴＧＣＴＡＣＡＡＴＧＧＧＣＡＧＡＡＣＡＡＡＧＧＧＣＡＧＣＧＡＡＧＣＣＧＣＧＡＧＧＣＴＡＡＧＣＣＡＡＴＣＣＣＡＣＡＡＡＴＣＴＧＴＴＣＴＣＡＧＴＴＣＧＧＡＴＣＧＣＡＧＴＣＴＧＣＡＡＣＴＣＧＡＣＴＧＣＧＴＧＡＡＧＣＴＧＧＡＡＴＣＧＣＴＡＧＴＡＡＴＣＧＣＧＧＡＴＣＡＧＣＡＴＧＣＣＧＣＧＧＴＧＡＡＴＡＣＧＴＴＣＣＣＧＧＧＣＣＴＴＧＴＡＣＡＣＡＣＣＧＣＣＣＧＴＣＡＣＡＣＣＡＣＧＡＧＡＧＴＴＴＧＴＡＡＣＡＣＣＣＧＡＡＧＴＣＧＧＴＧＡＧＧＴＡＡＣＣＴＴＴＴＧＧＡＧＣＣＡＧＣＣＧＣＣＧＡＡＧＧＴＧＧＧＡＣＡＧＡＴＧＡＴＴＧＧＧＧＴＧＡＡＧＴＣＧＴＡＣＡＧＧＧＡＡＡＡ
Sequence number 1:
AGGGCTTCCCCTTCGGGGGCAGAGTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGATCTTAGTTGCCAGCATTCAGTTGGGCACTCTAAGGTGACTGCCGGTGACAAACCGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTGCTACAATGGGCAGAACAAAGGGCAGCGAAGCCGCGAGGCTAAGCCAATCCCACAAATCTGTTCTCAGTTCGGATCGCAGTCTGCAACTCGACTGCGTGAAGCTGGAATCGCTAGTAAT GCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCACGAGAGTTTGTAACACCCGAAGTCGGTGAGGTAACCTTTTGGAGCCAGCCGCCGAAGGTGGGACAGATGATTGGGGTGAAGTCGTACAGGGAAAA
前記菌株は、α−グルコシダーゼ阻害剤を腸内で高収率で生産可能な嫌気性特性と生体外でもα−グルコシダーゼ阻害剤を生産可能な好気的特性とを同時に有しうる。 The strain may simultaneously have anaerobic characteristics capable of producing an α-glucosidase inhibitor in a high yield in the intestine and aerobic characteristics capable of producing an α-glucosidase inhibitor ex vivo.
前記菌株は、胞子を形成し、腸内に固着せず、一時的に生息する特性を示して、必要に応じて投与された菌株の除去が可能であって、安全に使用することができる。望ましくは、前記菌株は、生物体に投与された後、２週経過する時点に生物体外に***され、より望ましくは、１週経過する時点に***されうる。 The strain forms spores, does not stick in the intestine, exhibits a property of temporary inhabiting, enables removal of the strain administered as needed, and can be used safely. Preferably, the strain is excreted from the body at two weeks after administration to an organism, and more preferably, excreted at one week.
また、前記菌株は、腸内で前記α−グルコシダーゼ阻害剤を生産することができて、α−グルコシダーゼ阻害剤の有効濃度を一定に保持し、腸内で生産した前記α−グルコシダーゼ阻害剤は、***が可能であって、安全に使用することができる。望ましくは、前記α−グルコシダーゼ阻害剤は、菌株が生物体に投与された後、２週経過する時点に生物体外に***されうる。 In addition, the strain can produce the α-glucosidase inhibitor in the intestine, keep an effective concentration of the α-glucosidase inhibitor constant, and the α-glucosidase inhibitor produced in the intestine is It can be excreted and can be used safely. Desirably, the α-glucosidase inhibitor can be excreted outside the organism two weeks after the strain is administered to the organism.
これにより、前記菌株を含む食品を摂取する方法によって投与して、腸内でα−グルコシダーゼ阻害剤を高収率で生産することができて、生物体外に排出が可能であって、体重減量と血糖降下との目的として効果的に使用することができる。 Thus, it is possible to produce an α-glucosidase inhibitor with high yield in the intestine by administration by a method of ingesting a food containing the above-mentioned strain, to be excreted outside the organism, and to lose weight. It can be used effectively for the purpose of hypoglycemia.
本発明は、前記菌株を含む食品組成物を提供する。 The present invention provides a food composition comprising the strain.
前記食品組成物は、通用されるバチルス・リケニフォルミスの培養方法によって培養された菌株、菌株の胞子または菌株の発酵物を含みうる。 The food composition may comprise a strain cultured by a commonly used Bacillus licheniformis culture method, a spore of the strain, or a fermented product of the strain.
一例として、前記食品組成物は、前記菌株の胞子を含み、前記食品組成物は、１ｋｇ当たり１０６〜１０１０個の胞子であって、前記菌株を含んで前記菌株が、腸内でα−グルコシダーゼ阻害剤を多量生産することができる。 As an example, the food composition comprises spores of the strain, the food composition is 10 6 to 10 10 spores per kg, the strain comprising the strain, the strain comprising α- A large amount of glucosidase inhibitor can be produced.
さらに他の例として、前記食品組成物は、前記菌株の発酵物をさらに含み、前記発酵物は、前記菌株を大豆に接種して発酵した大豆発酵物であり得る。 As still another example, the food composition may further include a fermented product of the strain, and the fermented product may be a fermented soybean fermented by inoculating soybean with the strain.
以下、本発明を実施例を挙げてより詳しく説明する。 Hereinafter, the present invention will be described in more detail by way of examples.
提示された実施例は、本発明の具体的な例示であり、本発明の範囲を制限するためのものではない。 The presented examples are specific illustrations of the present invention and are not intended to limit the scope of the present invention.
＜実施例＞
１．菌株の探索
韓国、中国、日本、米国など世界各地から収集した約５００余点の稲わら及び乾草を試料として微生物を分離した。各試料を滅菌食塩水に少量加えて懸濁させた後、８０℃恒温水槽で２０分間熱処理して得た胞子液を２％寒天を含有するＬＢ平板培地（１％トリプトン、０．２％砂糖、０．５％酵母抽出物及び０．５％ ＮａＣｌ、ｐＨ７．０）に塗抹し、５５℃培養器で２日間嫌気的に培養し、培養後、菌集落を形成する菌体を分離した。α−グルコシダーゼ阻害剤の生産量を調査するために、分離された菌株を５ｍｌの５％大豆粉を懸濁した培地に接種し、３７℃で２４時間培養した。培養液を遠心分離して、上澄み液からα−グルコシダーゼ阻害剤活性を測定した（表１の好気的培養）。前記の過程で約６０種の通性嫌気性細菌をα−グルコシダーゼ阻害剤生産菌として１次選抜した後、５０℃で嫌気的に生育が可能であり、プロピオン酸（ｐｒｏｐｉｏｎｉｃ ａｃｉｄ）を磁化する菌株を選抜して、α−グルコシダーゼ阻害活性が高い３種を２次選抜し、培養液を遠心分離して、上澄み液からα−グルコシダーゼ阻害剤活性を測定した（表１の嫌気的培養）。前記３種の菌株は、バージェイズマニュアル（Ｂｅｒｇｅｙ’ｓ Ｍａｎｕａｌ ｏｆ Ｓｙｓｔｅｍａｔｉｃ Ｂａｃｔｅｒｉｏｌｏｇｙ、２００２）による分類学的特性の分析方法によって分類し、そのうち、１種が食用可能な菌であるバチルス・リケニフォルミス（Ｂａｃｉｌｌｕｓ ｌｉｃｈｅｎｉｆｏｒｍｉｓ）に同定されてバチルス・リケニフォルミスＮＹ１５０５と名付け、前記菌株が、下記の配列番号１の１６Ｓ ＲＮＡ配列を有するということを確認し、前記配列を韓国生命工学研究院生物資源センター（ＫＣＴＣ）に２０１６年５月３日付で寄託した（寄託番号：ＫＣＴＣ１３０２１ＢＰ）。
<Example>
1. Screening of Strains Microorganisms were isolated using rice straw and hay of about 500 points collected from various parts of the world such as Korea, China, Japan, and the United States. A small amount of each sample is added to sterile saline and suspended, and heat treated at 80 ° C. in a constant temperature water bath for 20 minutes to obtain a spore solution obtained by LB plate medium containing 2% agar (1% tryptone, 0.2% sugar) The cells were smeared with 0.5% yeast extract and 0.5% NaCl, pH 7.0), and anaerobically cultured in a 55 ° C. incubator for 2 days, and after cultivation, the bacterial cells forming bacterial colonies were separated. In order to investigate the production amount of α-glucosidase inhibitor, the isolated strain was inoculated into a medium in which 5 ml of 5% soy flour was suspended, and cultured at 37 ° C. for 24 hours. The culture solution was centrifuged, and α-glucosidase inhibitor activity was measured from the supernatant (aerobic culture in Table 1). After primary selection of about 60 types of facultative anaerobes as α-glucosidase inhibitor-producing bacteria in the above process, a strain capable of anaerobically growing at 50 ° C. and magnetizing propionic acid Were selected, and 3 kinds having high .alpha.-glucosidase inhibitory activity were secondarily selected, and the culture solution was centrifuged to measure .alpha.-glucosidase inhibitor activity from the supernatant (anaerobic culture in Table 1). The three strains are classified according to the method of analysis of taxonomical characteristics according to Bergey's Manual of Systematic Bacteriology (2002), and one of the three strains is Bacillus licheniformis (Bacillus licheniformis), which is an edible fungus. Identified as Bacillus licheniformis NY 1505, and confirmed that the strain has the 16S RNA sequence of SEQ ID NO: 1 below, and the said sequence was submitted to Korea Biotech Research Institute BioResource Center (KCTC) 2016 Deposited on May 3 (Deposit No .: KCTC13021BP).
配列番号１：
ＡＧＧＧＣＴＴＣＣＣＣＴＴＣＧＧＧＧＧＣＡＧＡＧＴＧＡＣＡＧＧＴＧＧＴＧＣＡＴＧＧＴＴＧＴＣＧＴＣＡＧＣＴＣＧＴＧＴＣＧＴＧＡＧＡＴＧＴＴＧＧＧＴＴＡＡＧＴＣＣＣＧＣＡＡＣＧＡＧＣＧＣＡＡＣＣＣＴＴＧＡＴＣＴＴＡＧＴＴＧＣＣＡＧＣＡＴＴＣＡＧＴＴＧＧＧＣＡＣＴＣＴＡＡＧＧＴＧＡＣＴＧＣＣＧＧＴＧＡＣＡＡＡＣＣＧＧＡＧＧＡＡＧＧＴＧＧＧＧＡＴＧＡＣＧＴＣＡＡＡＴＣＡＴＣＡＴＧＣＣＣＣＴＴＡＴＧＡＣＣＴＧＧＧＣＴＡＣＡＣＡＣＧＴＧＣＴＡＣＡＡＴＧＧＧＣＡＧＡＡＣＡＡＡＧＧＧＣＡＧＣＧＡＡＧＣＣＧＣＧＡＧＧＣＴＡＡＧＣＣＡＡＴＣＣＣＡＣＡＡＡＴＣＴＧＴＴＣＴＣＡＧＴＴＣＧＧＡＴＣＧＣＡＧＴＣＴＧＣＡＡＣＴＣＧＡＣＴＧＣＧＴＧＡＡＧＣＴＧＧＡＡＴＣＧＣＴＡＧＴＡＡＴＣＧＣＧＧＡＴＣＡＧＣＡＴＧＣＣＧＣＧＧＴＧＡＡＴＡＣＧＴＴＣＣＣＧＧＧＣＣＴＴＧＴＡＣＡＣＡＣＣＧＣＣＣＧＴＣＡＣＡＣＣＡＣＧＡＧＡＧＴＴＴＧＴＡＡＣＡＣＣＣＧＡＡＧＴＣＧＧＴＧＡＧＧＴＡＡＣＣＴＴＴＴＧＧＡＧＣＣＡＧＣＣＧＣＣＧＡＡＧＧＴＧＧＧＡＣＡＧＡＴＧＡＴＴＧＧＧＧＴＧＡＡＧＴＣＧＴＡＣＡＧＧＧＡＡＡＡ
Sequence number 1:
AGGGCTTCCCCTTCGGGGGCAGAGTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGATCTTAGTTGCCAGCATTCAGTTGGGCACTCTAAGGTGACTGCCGGTGACAAACCGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTGCTACAATGGGCAGAACAAAGGGCAGCGAAGCCGCGAGGCTAAGCCAATCCCACAAATCTGTTCTCAGTTCGGATCGCAGTCTGCAACTCGACTGCGTGAAGCTGGAATCGCTAGTAAT GCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCACGAGAGTTTGTAACACCCGAAGTCGGTGAGGTAACCTTTTGGAGCCAGCCGCCGAAGGTGGGACAGATGATTGGGGTGAAGTCGTACAGGGAAAA
２．納豆の製造
大豆を常温で１２時間ふやかした後、１２１℃で４０分間煮た。煮た大豆を冷却する前、ｇ当たり１０３匹の胞子を接種した後、５０ｇずつ納豆製造用発泡スチレン容器に入れ、ビニールカバーを被せた後、３７℃で２０時間培養した。該培養された納豆を１２時間冷蔵保管した後、α−グルコシダーゼ阻害活性を測定及び官能評価を行った。（表１の納豆）。
2. Production of natto After soaking the soybeans at room temperature for 12 hours, it was boiled at 121 ° C. for 40 minutes. Before cooling the boiled soybean, following inoculation with g per 10 Three spores, 50g each placed in natto manufacturing styrofoam container, after covered with vinyl cover, and 20 hours at 37 ° C.. The cultured natto was stored under refrigeration for 12 hours, and then the α-glucosidase inhibitory activity was measured and subjected to sensory evaluation. (Natto in Table 1).
３．α−グルコシダーゼ阻害活性の測定
α−グルコシダーゼは、豚の小腸から抽出して部分精製したものを酵素源として使用した。α−グルコシダーゼ酵素液は、２４ｕｎｉｔ／ｍｌになるように０．５Ｍリン酸塩緩衝溶液（ｐｏｔａｓｓｉｕｍ ｐｈｏｓｐｈａｔｅ ｂｕｆｆｅｒ、ｐＨ７．０）に適当に希釈して使用し、基質は、ｐ−ニトロフェニルα−Ｄ−グルコピラノシド（ｐ−ｎｉｔｒｏｐｈｅｎｙｌ α−Ｄ−ｇｌｕｃｏｐｙｒａｎｏｓｉｄｅ、ｐＮＰＧ）を利用した。試験管に培養上澄み液３０μｌと酵素５０μｌとを混ぜて３７℃で１０分間予備保温を行った後、３ｍＭ ｐＮＰＧ ５０μｌを添加し、３７℃で２０分間反応させた。反応液に０．１Ｍ Ｎａ２ＣＯ３を加えて反応を停止し、４０５ｎｍで吸光度を測定して、下記数式１で阻害活性を測定し、α−グルコシダーゼ阻害活性の測定結果を下記の表１に示した。この際、α−グルコシダーゼ阻害単位（α−ｇｌｕｃｏｓｉｄａｓｅ ｉｎｈｉｂｉｔｉｏｎ ｕｎｉｔ、ＡＧＩ ｕｎｉｔ）は、下記数式１で活性測定に使われたα−グルコシダーゼ（α−ｇｌｕｃｏｓｉｄａｓｅ）を１００％阻害する時の阻害剤の量と定義した。
3. Measurement of α-Glucosidase Inhibitory Activity α-Glucosidase was extracted from pig small intestine and partially purified was used as an enzyme source. The α-glucosidase enzyme solution is suitably diluted in 0.5 M phosphate buffer solution (potassium phosphate buffer, pH 7.0) to be 24 units / ml, and the substrate is p-nitrophenyl α-D. -A glucopyranoside (p-nitrophenyl alpha-D-glucocopyranoside, pNPG) was utilized. In a test tube, 30 μl of the culture supernatant and 50 μl of enzyme were mixed and pre-incubated at 37 ° C. for 10 minutes, 50 μl of 3 mM pNPG was added, and the reaction was allowed to react at 37 ° C. for 20 minutes. The reaction is stopped by adding 0.1 M Na 2 CO 3 to the reaction solution, the absorbance is measured at 405 nm, the inhibitory activity is measured by the following formula 1, and the measurement results of α-glucosidase inhibitory activity are shown in Table 1 below. Indicated. At this time, the α-glucosidase inhibition unit (α-glucosidase inhibition unit, AGI unit) is the amount of inhibitor when inhibiting 100% of α-glucosidase (α-glucosidase) used for activity measurement in the following formula 1 Defined.
表１に示されたように、酸素の供給有無に関係なく、均一なＡＧＩ阻害活性を示して、バチルス・リケニフォルミスが通性嫌気性細菌なので、嫌気的な条件でも生育が可能であるという事実を確認することができた。したがって、動物の腸管内でバチルス・リケニフォルミスは、増殖を行い、有用な生理活性物質を生産することができると確認された。 As shown in Table 1, regardless of the supply of oxygen, it shows uniform AGI inhibitory activity, and because Bacillus licheniformis is a facultative anaerobic bacterium, it can be grown under anaerobic conditions. I was able to confirm. Therefore, it was confirmed that Bacillus licheniformis can grow and produce useful physiologically active substances in the intestinal tract of animals.
４．バチルス・リケニフォルミスＮＹ１５０５菌株の食餌実験
バチルス・リケニフォルミスＮＹ１５０５菌株が、動物の腸管内で有用物質を生産するか否かを確認するために、マウスの飼料にバチルス・リケニフォルミスＮＹ１５０５胞子を混合して投与することにより、バチルス・リケニフォルミスＮＹ１５０５菌株の腸内増殖有無、腸内でのα−グルコシダーゼ阻害剤の生成有無などを検討した。
4. Dietary experiment of Bacillus licheniformis strain NY1505 strain In order to confirm whether Bacillus licheniformis strain NY1505 produces useful substances in the intestinal tract of animals, mice should be mixed with Bacillus licheniformis strain NY1505 spores in their diet. Thus, the presence or absence of enteric growth of Bacillus licheniformis NY1505 strain, the presence or absence of formation of an α-glucosidase inhibitor in the gut, and the like were examined.
まず、α−グルコシダーゼ阻害剤を生産するバチルス・リケニフォルミスＮＹ１５０５菌株の胞子を混合した飼料（１０８胞子／ｋｇ飼料）をマウスに給与し、体重の変化を観察した。このために、販売される標準飼料と水とを自在に給与し、雄マウス（００週齢）を１週間予備飼育した後に使用した。明暗サイクルは、午前０８：００時から午後２０：００を明期、午後２０：００から午前０８：００を暗期にし、２２．５±０．５℃の温度及び５０〜６０％の湿度が保持される環境下で飼育した。肥満誘導式で下記表２及び表３の高炭水化物食餌と高脂肪食餌とにし、バチルス・リケニフォルミスＮＹ１５０５菌株の胞子が含有された飼料は、それぞれの肥満誘導式１ｋｇ当たり１０８胞子を混合して製造した。マウスは、５個の群（各８匹）に分けて、対照群、高炭水化物食餌群、高炭水化物食餌＋胞子群、高脂肪食餌群、高脂肪食餌＋胞子群に分けて、それぞれ７週間飼育した。 First, a diet (10 8 spores / kg diet) mixed with spores of Bacillus licheniformis NY1505 strain producing an α-glucosidase inhibitor was fed to mice, and a change in body weight was observed. For this purpose, a standard diet and water to be sold were freely fed, and male mice (00-week-old) were used after preliminary breeding for one week. The light and dark cycle is from 08:00 am to 20:00 pm, and from 20:00 pm to 08:00 am in the dark, with a temperature of 22.5 ± 0.5 ° C. and a humidity of 50 to 60%. The animals were bred under the maintained environment. A diet containing a high carbohydrate diet and a high fat diet shown in Tables 2 and 3 below and containing spores of Bacillus licheniformis strain NY1505 was prepared by mixing 10 8 spores per kg of each obesity induction formula. did. The mice are divided into 5 groups (8 each) and divided into control group, high carbohydrate diet group, high carbohydrate diet + spore group, high fat diet group, high fat diet + spore group, and reared for 7 weeks each did.
（１）高炭水化物食餌の給与時に、バチルス・リケニフォルミスＮＹ１５０５菌胞子の投与がマウスの体重に及ぼす影響分析
高炭水化物食餌給与されたマウスの体重（ｂｏｄｙ ｗｅｉｇｈｔ、単位ｇｒａｍ）にバチルス・リケニフォルミスＮＹ１５０５菌胞子の投与が及ぼす影響を分析した結果、図１に示されたように、高炭水化物飼料群は、対照群に比べて、明らかな体重増加を示すが、バチルス・リケニフォルミスＮＹ１５０５菌株の胞子が混合された高炭水化物飼料群では、対照群と同様の体重増加の態様を示すことを確認することができた。
(1) Analysis of the effect of Bacillus licheniformis NY1505 bacterial spores on the body weight of mice when fed a high carbohydrate diet: analysis of Bacillus licheniformis NY1505 bacterial spores on the body weight (unit gram) of mice fed a high carbohydrate diet As a result of analyzing the influence of the administration, as shown in FIG. 1, the high carbohydrate diet group shows a clear weight gain as compared to the control group, but the spores of Bacillus licheniformis strain NY1505 strain are mixed. In the carbohydrate diet group, it could be confirmed to exhibit the same aspect of weight gain as the control group.
（２）高脂肪食餌の給与時に、バチルス・リケニフォルミスＮＹ１５０５菌胞子の投与がマウスの体重に及ぼす影響
高脂肪食餌給与されたマウスの体重にバチルス・リケニフォルミスＮＹ１５０５菌胞子の投与がマウスの体重に及ぼす影響を分析した結果、図２に示されたように、高脂肪飼料群は、対照群に比べて、明らかな体重増加を示すが、バチルス・リケニフォルミスＮＹ１５０５菌株の胞子が混合された高脂肪飼料群では、対照群と同様の体重増加の態様を示すことを確認することができた。
(2) Effects of administration of Bacillus licheniformis NY1505 bacterial spore on the body weight of mice at the time of feeding a high fat diet Effect of administration of Bacillus licheniformis NY1505 bacterial spores on the body weight of a high fat diet fed mouse As a result of analysis, as shown in FIG. 2, the high fat diet group shows a clear weight gain compared to the control group, but in the high fat diet group mixed with spores of Bacillus licheniformis strain NY1505. It could be confirmed to show the aspect of weight gain similar to the control group.
（３）糞便で***されるバチルス・リケニフォルミスＮＹ１５０５菌数の変化
バチルス・リケニフォルミスＮＹ１５０５菌胞子が投与されたマウスの便に含まれた胞子数を測定して、便で***される菌株の変化を分析した結果、図３に示されたように、飼料１ｇ当たり１０５匹の胞子が混合されており、一匹当たり一日に約５ｇの飼料を摂取するので、一日に約５ｘ１０５匹の胞子を摂取する。胞子投与３週後には、糞便１ｇ当たり約１０７匹のバチルス・リケニフォルミスＮＹ１５０５が検出されるので、腸内で本菌株が旺盛に増殖して排出されることが分かった。胞子を７週間投与した場合、胞子を投与していない１週間である８週次には、菌の数字が格段に減少するので、腸内に固着せず、一時的に生息すると判断することができた。したがって、本菌株の投与を中断すれば、腸内菌叢の変化が予想されるので、必要に応じて腸内で本菌株の除去も可能な長所があるということを確認することができた。
(3) Changes in the number of Bacillus licheniformis NY1505 bacteria excreted in feces The number of spores contained in stools of mice treated with Bacillus licheniformis NY1505 bacteria spores is measured to analyze changes in fecal excremented strains. as a result, as shown in FIG. 3, 10 five spores per feed 1g are mixed, since intake of feed of approximately 5g per day per animal, about 5x10 five spores per day To take Three weeks after spore administration, approximately 10 7 B. licheniformis NY 1505 were detected per gram of feces, so it was found that the present strain proliferated and was excreted in the intestine. When spore is administered for 7 weeks, after 8 weeks which is 1 week when spores are not administered, the number of bacteria decreases significantly, so it can be judged that it does not stick in the intestine and that it temporarily inhabits did it. Therefore, it was possible to confirm that there is an advantage that if the administration of this strain is discontinued, changes in the intestinal flora can be expected, and that this strain can be removed in the intestine if necessary.
（４）便で***されるα−グルコシダーゼ阻害活性の変化
バチルス・リケニフォルミスＮＹ１５０５菌胞子が投与されたマウスの便に含まれたα−グルコシダーゼの阻害活性を分析した結果、図４に示されたように、バチルス・リケニフォルミスＮＹ１５０５菌株は、便で排出される程度に腸内で旺盛に増殖し、α−グルコシダーゼ阻害剤を生産することを確認することができた。胞子が投与されたマウスの２週経過した時点の便で腸内で増殖したバチルス・リケニフォルミスＮＹ１５０５菌株が便で排出されて活性が検出された。また、４週次からは、７週までは排出されるバチルス・リケニフォルミスＮＹ１５０５菌株の量が安定化される時期に排出されるα−グルコシダーゼ阻害剤の量も一定していることを確認することができた。すなわち、α−グルコシダーゼ阻害剤は、常に腸内で生産されるので、腸内での濃度が一定量保持され、効率が高く作用する長所を有し、生産された阻害剤の一定量が排出されることが分かる。糞便で排出されるα−グルコシダーゼ阻害剤の活性を見れば、バチルス・リケニフォルミスＮＹ１５０５菌株で製造した納豆の活性（表１）と比べると、相当量のα−グルコシダーゼ阻害剤が腸内で生産され、その一部が排出されるという事実を確認することができた。
(4) Changes in the α-glucosidase inhibitory activity excreted in feces As a result of analyzing the inhibitory activity of α-glucosidase contained in feces of mice administered with Bacillus licheniformis NY1505 bacterial spore, as shown in FIG. In addition, it was possible to confirm that Bacillus licheniformis strain NY1505 grows vigorously in the intestine to the extent that it is excreted in feces and produces an α-glucosidase inhibitor. Two weeks after passage of the spore-administered mice, B. licheniformis strain NY1505 grown in the intestine was feces out of the stool and activity was detected. In addition, it is to be confirmed that the amount of α-glucosidase inhibitor which is excreted at the time when the amount of Bacillus licheniformis NY1505 strain excreted is stabilized from the fourth week onward is also constant until seven weeks. did it. That is, since the α-glucosidase inhibitor is always produced in the intestine, it has the advantage that the concentration in the intestine is maintained at a constant amount and the efficiency is high, and a certain amount of the produced inhibitor is excreted. It can be understood that As for the activity of the α-glucosidase inhibitor excreted in feces, a considerable amount of the α-glucosidase inhibitor is produced in the intestine, as compared with the activity of natto produced by Bacillus licheniformis strain NY1505 (Table 1). It was possible to confirm the fact that part of it was discharged.
前記のような結果を通じて、本発明によるバチルス・リケニフォルミスＮＹ１５０５菌株が発酵によって生成された生理活性物質を使用することではなく、体内で菌株が生理活性物質を連続して作って供給するので、α−グルコシダーゼ阻害剤の生成のための別途の発酵コスト及び加工費が不要であって、生産コストを節減し、体内で連続して生産することにより、有効な濃度を一定に保持できるという長所があるということを確認することができ、有用菌の胞子を利用することにより、発酵臭などの問題が発生せず、多様な加工食品に添加物として使用することができるので、多様な形態の食品に適用することができるという事実を確認することができた。 As described above, since Bacillus licheniformis strain NY1505 according to the present invention does not use the physiologically active substance produced by fermentation, the strain continuously produces and supplies the physiologically active substance in the body. There is no need for additional fermentation and processing costs for the production of glucosidase inhibitors, which has the advantage of being able to reduce the cost of production and keep the effective concentration constant by continuous production in the body By using spores of useful bacteria, it can be confirmed that it can be used as an additive in various processed foods without causing problems such as fermented odor, so it is applied to various forms of food I was able to confirm the fact that I can.
５．分離された菌株の形態学的及び生化学的特性の究明
（１）分離された菌株の形態学的特性
前記のように分離されたバチルス・リケニフォルミスＮＹ１５０５菌株は、ＬＢ寒天平板培地でコロニーの中央部分は薄いさび色を示し、縁部は不規則な外形を示した（図５）。菌の生育が可能な温度範囲は、２５〜５０℃の範囲で成長が良好であり、６０℃以上では、菌体成長が確認されていない。ＬＢ液体培地を利用した菌体成長の対数期で顕微鏡観察した結果、グラム陽性の短い棒状を示せれば、比較菌株であるバチルス・リケニフォルミスと類似した。また、分離した菌株は、下記表４に示されたように、グラム陽性であり、細胞のサイズは、ほぼ０．５〜０．７×１．５〜１．８μｍであることを確認することができ、前記結果を総合して、バチルス・リケニフォルミスＮＹ１５０５菌株の分類学上の位置を図６に示した。
5. Determination of morphological and biochemical characteristics of the isolated strain (1) Morphological characteristics of the isolated strain Bacillus licheniformis NY1505 strain isolated as described above is a center portion of the colony on LB agar plate medium Had a light rust color and the edges had an irregular contour (FIG. 5). The temperature range in which the bacteria can grow is good in the range of 25 to 50 ° C., and at 60 ° C. or more, cell growth is not confirmed. As a result of microscopic observation in the logarithmic phase of cell growth using LB liquid medium, it was similar to the comparative strain Bacillus licheniformis if a gram-positive short rod is shown. Also, as shown in Table 4 below, the isolated strain is gram positive, and it is confirmed that the cell size is approximately 0.5 to 0.7 × 1.5 to 1.8 μm. By combining the above results, the taxonomic position of Bacillus licheniformis strain NY1505 is shown in FIG.
（２）分離された菌株の生化学的特性
バージェイズマニュアルによるバチルス属菌株の分類学的特性の分析方法とＡＰＩ５０ＣＨＢキット（ＢｉｏＭｅｒｉｅｕｘ社、Ｆｒａｎｃｅ）とを使用して、分離された菌株の生化学的特性などを調査した結果、分離した菌株は、グラム陽性の円筒状であって、胞子は細胞中央に形成され、硝酸塩の還元力は陽性であり、インドール形成は陰性であった。また、カゼインと澱粉とを分解し、カタラーゼ陽性であり、好気的条件及び嫌気的条件で成長すると確認され、下記表５に示すような生化学的特性（ＡＰＩ ｔｅｓｔ結果）を有することを確認することができた。
(2) Biochemical characterization of the isolated strain Biochemical analysis of the strain isolated using the method of analysis of taxonomic characteristics of Bacillus spp. According to the Bar-Jes manual and the API 50 CHB kit (BioMerieux, France) As a result of investigating characteristics and the like, the isolated strain was a gram-positive cylinder, spores were formed in the center of the cell, the reducing power of nitrate was positive, and indole formation was negative. It is also confirmed that it decomposes casein and starch, is catalase-positive, grows under aerobic and anaerobic conditions, and has biochemical characteristics (API test result) as shown in Table 5 below. We were able to.
本発明によるバチルス・リケニフォルミスＮＹ１５０５菌株は、腸内でα−グルコシダーゼ阻害剤を生産して供給するので、食品組成物に使われる。
The Bacillus licheniformis NY1505 strain according to the present invention is used in food compositions because it produces and supplies an α-glucosidase inhibitor in the intestine.
寄託機関名：韓国生命工学研究院韓国生物資源センター（ＫＣＴＣ）
受託番号：ＫＣＴＣ１３０２１ＢＰ
受託日：２０１６０５０３
Depositary institution name: Korea BioResource Institute Korea BioResource Center (KCTC)
Accession No .: KCTC13021BP
Date of acceptance: 20160503
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