JP2022022349A - Methods for producing equol-containing compositions - Google Patents
Methods for producing equol-containing compositions Download PDFInfo
- Publication number
- JP2022022349A JP2022022349A JP2021198799A JP2021198799A JP2022022349A JP 2022022349 A JP2022022349 A JP 2022022349A JP 2021198799 A JP2021198799 A JP 2021198799A JP 2021198799 A JP2021198799 A JP 2021198799A JP 2022022349 A JP2022022349 A JP 2022022349A
- Authority
- JP
- Japan
- Prior art keywords
- equol
- aglycone
- enzyme
- containing composition
- isoflavones
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- ADFCQWZHKCXPAJ-GFCCVEGCSA-N equol Chemical compound C1=CC(O)=CC=C1[C@@H]1CC2=CC=C(O)C=C2OC1 ADFCQWZHKCXPAJ-GFCCVEGCSA-N 0.000 title claims abstract description 100
- 235000019126 equol Nutrition 0.000 title claims abstract description 100
- ADFCQWZHKCXPAJ-UHFFFAOYSA-N indofine Natural products C1=CC(O)=CC=C1C1CC2=CC=C(O)C=C2OC1 ADFCQWZHKCXPAJ-UHFFFAOYSA-N 0.000 title claims abstract description 100
- 239000000203 mixture Substances 0.000 title claims abstract description 54
- 238000000034 method Methods 0.000 title claims abstract description 34
- 108090000790 Enzymes Proteins 0.000 claims abstract description 68
- 102000004190 Enzymes Human genes 0.000 claims abstract description 68
- 244000005700 microbiome Species 0.000 claims abstract description 68
- CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 claims abstract description 42
- 235000008696 isoflavones Nutrition 0.000 claims abstract description 42
- 239000013566 allergen Substances 0.000 claims abstract description 23
- 238000004519 manufacturing process Methods 0.000 claims abstract description 21
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 claims description 41
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 claims description 41
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 claims description 41
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- ZQSIJRDFPHDXIC-UHFFFAOYSA-N Daidzein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC=C2C1=O ZQSIJRDFPHDXIC-UHFFFAOYSA-N 0.000 claims description 25
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- 229930182470 glycoside Natural products 0.000 claims description 16
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- GMTUGPYJRUMVTC-UHFFFAOYSA-N Daidzin Natural products OC(COc1ccc2C(=O)C(=COc2c1)c3ccc(O)cc3)C(O)C(O)C(O)C=O GMTUGPYJRUMVTC-UHFFFAOYSA-N 0.000 claims description 9
- KYQZWONCHDNPDP-UHFFFAOYSA-N Daidzoside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 KYQZWONCHDNPDP-UHFFFAOYSA-N 0.000 claims description 9
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- MTXMHWSVSZKYBT-ASDZUOGYSA-N malonyldaidzin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](COC(=O)CC(O)=O)O[C@H]1OC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 MTXMHWSVSZKYBT-ASDZUOGYSA-N 0.000 claims description 4
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- GOMNOOKGLZYEJT-UHFFFAOYSA-N isoflavone Chemical compound C=1OC2=CC=CC=C2C(=O)C=1C1=CC=CC=C1 GOMNOOKGLZYEJT-UHFFFAOYSA-N 0.000 abstract description 5
- 239000001963 growth medium Substances 0.000 abstract description 4
- DKVBOUDTNWVDEP-NJCHZNEYSA-N teicoplanin aglycone Chemical compound N([C@H](C(N[C@@H](C1=CC(O)=CC(O)=C1C=1C(O)=CC=C2C=1)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)OC=1C=C3C=C(C=1O)OC1=CC=C(C=C1Cl)C[C@H](C(=O)N1)NC([C@H](N)C=4C=C(O5)C(O)=CC=4)=O)C(=O)[C@@H]2NC(=O)[C@@H]3NC(=O)[C@@H]1C1=CC5=CC(O)=C1 DKVBOUDTNWVDEP-NJCHZNEYSA-N 0.000 abstract 3
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Images
Abstract
Description
本発明は、エクオール含有組成物の製造方法に関する。 The present invention relates to a method for producing an equol-containing composition.
大豆には多くの大豆イソフラボン類が含まれており、これらイソフラボン類は、女性ホルモン作用(エストロゲン)や抗酸化作用を有し、イソフラボン類を摂取することにより、乳癌、前立腺癌、骨粗しょう症、高コレステロール血症、心疾患、更年期障害などに対して予防効果があることが明らかにされている(非特許文献1~6)。 Soybeans contain many soy isoflavones, and these isoflavones have female hormone action (estrogen) and antioxidant action, and by ingesting isoflavones, breast cancer, prostate cancer, osteoporosis, It has been clarified that it has a preventive effect on hypercholesterolemia, heart disease, menopausal disorders, etc. (Non-Patent Documents 1 to 6).
ところが一方で、大豆は日本の5大アレルギー食品の一つに挙げられており、大豆アレルギーは、大豆に含まれる貯蔵タンパク質中のアレルゲンタンパク質が原因で起こることが分かっている。1992年時点で、16種類の大豆アレルゲンタンパク質が同定されているが、アレルギーの出現頻度の高い主要アレルゲンは、Gly m Bd 30K、Gly m Bd 60K(7Sグロブリンα-サブユニット)およびGly m Bd 28Kであるとみられている。(非特許文献7)。そのため、大豆アレルゲンを低減化した大豆加工食品などの開発がなされている(特許文献1~3)。 On the other hand, however, soybeans are listed as one of the five major allergic foods in Japan, and it is known that soybean allergies are caused by allergen proteins in storage proteins contained in soybeans. As of 1992, 16 soybean allergen proteins have been identified, but the major allergens with the highest frequency of allergies are Gly m Bd 30K, Gly m Bd 60K (7S globulin α-subunit) and Gly m Bd 28K. Is believed to be. (Non-Patent Document 7). Therefore, processed soybean foods with reduced soybean allergens have been developed (Patent Documents 1 to 3).
近年の研究で、大豆をそのまま粉末化してイソフラボン類を測定すると、表1に示す12種類のイソフラボン類が存在し、そのうちダイジン、マロニルダイジン、ゲニスチン、マロニルゲニスチンが大部分を占めることが明らかにされた(非特許文献8)。 Recent studies have revealed that when soybeans are powdered as they are and isoflavones are measured, there are 12 types of isoflavones shown in Table 1, of which daidzin, malonyldaidzin, genistin, and malonylgenistin account for the majority. (Non-Patent Document 8).
更に、この大豆イソフラボン類における、上記女性ホルモン作用や抗酸化作用を発揮するための重要な活性本体は、ダイジンが体内で代謝されて、下記のように、ダイゼインからジヒドロダイゼインを経て生成するエクオールに主に由来することが分かってきた。すなわち、大豆内の主なイソフラボン類であるダイジンは、大豆中では糖と結合した配糖体の形で存在するが、この配糖体は、ヒトや動物の体内に入ると消化酵素又は腸内細菌の産生する酵素であるβ-グルコシダーゼ等の働きにより、ジヒドロダイゼインを経て、O-デスメチルアンゴレンシン又はエクオールへと酵素的に変換され、特に、エクオールはエストロゲン活性が高いことが知られている(非特許文献9及び10)。 Furthermore, in these soy isoflavones, the important active body for exerting the above-mentioned female hormone action and antioxidant action is equol, which is produced from daidzein via dihydrodaidzein when daidzin is metabolized in the body. It has been found that it is mainly derived from. That is, daidzein, which is the main isoflavone in soybeans, exists in soybeans in the form of glycosides bound to sugar, and these glycosides are digested enzymes or intestines when they enter the human or animal body. It is known that equol has high estrogen activity, and is enzymatically converted to O-desmethylangolencin or equol via dihydrodaidzein by the action of β-glucosidase, which is an enzyme produced by bacteria. (Non-Patent Documents 9 and 10).
ところが、人が大豆を食べても、その中に含まれるダイゼインを有効なエクオールにまで代謝する能力には個人差があり、日本人で約5割、欧米人で約3割程度の人しか代謝できないことも明らかとなっている(非特許文献11及び12)。そのため、代謝のできない人が、有効成分であるエクオールを直接摂取することができるように、エクオールを含有する大豆発酵物などが開発されており、そのうち大豆アレルゲンが低減されているものも開発されている(特許文献4~6)。 However, even if a person eats soybeans, there are individual differences in the ability to metabolize the daidzein contained in it to effective equol, and only about 50% of Japanese and about 30% of Westerners metabolize it. It is also clear that this is not possible (Non-Patent Documents 11 and 12). Therefore, fermented soybeans containing equol have been developed so that people who cannot metabolize can directly ingest equol, which is the active ingredient, and some of them have reduced soybean allergens. (Patent Documents 4 to 6).
ダイゼインを有効なエクオールにまで代謝できない人は、有効成分であるエクオールを直接摂取することが望ましい。しかしながら、アレルゲンを低減したエクオール含有発酵物等は開発されているものの、アレルギーを惹起しない、実質的にアレルゲンをフリーにしたものは未だ開発されていない。
本発明は、実質的にアレルゲンを含まないエクオール含有組成物の製造方法の提供を課題とする。
People who cannot metabolize daidzein to effective equol should take the active ingredient equol directly. However, although equol-containing fermented products with reduced allergens have been developed, those that do not cause allergies and are substantially free of allergens have not yet been developed.
An object of the present invention is to provide a method for producing an equol-containing composition that is substantially free of allergens.
本発明者らは、上記知見に基づき更に検討を進め、実質的にアレルゲンを含まないエクオール含有組成物を得る方法を検討したところ、イソフラボン類を特定の酵素で処理し、その後に特定の微生物で発酵させることにより、これを達成できることに想到し、本発明を完成させた。すなわち、本発明は以下に示すとおりである。 Based on the above findings, the present inventors further studied and investigated a method for obtaining an equol-containing composition substantially free of allergens. As a result, isoflavones were treated with a specific enzyme, and then with a specific microorganism. We came up with the idea that this could be achieved by fermenting, and completed the present invention. That is, the present invention is as shown below.
〔1〕(1)マメ科植物の植物体に由来するイソフラボン類を、前記イソフラボン類をアグリコンに変換する酵素で処理する工程、(2)前記工程(1)で得られた前記アグリコンを含有する培地で嫌気性微生物を培養し、前記嫌気性微生物により、前記アグリコンをエクオールに変換する工程、及び、(3)前記工程(2)で産生された前記エクオールを含有するエクオール含有組成物を、前記培地から回収する工程、を含む、エクオール含有組成物の製造方法。
〔2〕前記マメ科植物が、大豆、クズ、レッドクローバー、及びカンゾウからなる群から選ばれる1種以上である、〔1〕に記載の方法。
〔3〕前記マメ科植物の植物体が大豆胚軸である、〔1〕または〔2〕に記載の方法。
〔4〕前記イソフラボン類がアグリコン配糖体である、〔1〕~〔3〕のいずれかに記載の方法。
〔5〕前記アグリコン配糖体が、ダイジン、アセチルダイジン、マロニルダイジン及びスクシニルダイジンからなる群から選ばれる1種以上である、〔4〕に記載の方法。
〔6〕前記嫌気性微生物が、アサッカロバクター・セラツス(Asaccharobacter celatus
)DSM 18785の16S rDNAと95%以上の同一性を有する16S rDNAを保有
する微生物である、〔1〕~〔5〕のいずれかに記載の方法。
〔7〕前記嫌気性微生物が、アサッカロバクター(Asaccharobacter)属、スラッキア(Slackia)属、またはアドレクラウチア(Adlercreutzia)属に分類される微生物である、
〔1〕~〔6〕のいずれかに記載の方法。
〔8〕前記酵素がβ-グルコシダーゼ又はペクチナーゼである、〔1〕~〔7〕のいずれかに記載の方法。
〔9〕〔1〕~〔8〕のいずれかに記載の方法により製造されたエクオール含有組成物を含む化粧料。
〔10〕〔1〕~〔8〕のいずれかに記載の方法により製造されたエクオール含有組成物を含む医薬。
〔11〕〔1〕~〔8〕のいずれかに記載の方法により製造されたエクオール含有組成物を含む食品。
[1] (1) A step of treating isoflavones derived from a plant of a legume family with an enzyme that converts the isoflavones into aglycone, (2) containing the aglycone obtained in the step (1). A step of culturing an anaerobic microorganism in a medium and converting the aglycone into equol by the anaerobic microorganism, and (3) an equol-containing composition containing the equol produced in the step (2). A method for producing an equol-containing composition, which comprises a step of recovering from the medium.
[2] The method according to [1], wherein the legume is at least one species selected from the group consisting of soybean, kudzu, red clover, and licorice.
[3] The method according to [1] or [2], wherein the leguminous plant is a soybean hypocotyl.
[4] The method according to any one of [1] to [3], wherein the isoflavones are aglycone glycosides.
[5] The method according to [4], wherein the aglycone glycoside is at least one selected from the group consisting of daidzin, acetyl daidzin, malonyl daidzin and succinyl daidzin.
[6] The anaerobic microorganism is Asaccharobacter celatus.
) The method according to any one of [1] to [5], which is a microorganism having 16S rDNA having 95% or more identity with 16S rDNA of DSM 18785.
[7] The anaerobic microorganism is a microorganism classified into the genus Asaccharobacter, the genus Slackia, or the genus Adlercreutzia.
The method according to any one of [1] to [6].
[8] The method according to any one of [1] to [7], wherein the enzyme is β-glucosidase or pectinase.
[9] A cosmetic containing an equol-containing composition produced by the method according to any one of [1] to [8].
[10] A medicine containing an equol-containing composition produced by the method according to any one of [1] to [8].
[11] A food containing an equol-containing composition produced by the method according to any one of [1] to [8].
本発明によれば、実質的にアレルゲンを含まないエクオール含有組成物の製造方法を提供することができる。 According to the present invention, it is possible to provide a method for producing an equol-containing composition that is substantially free of allergens.
以下、本発明について、具体的な態様を示しながら詳細に説明するが、本発明は例示する具体的態様に限定されないことはいうまでもない。 Hereinafter, the present invention will be described in detail while showing specific embodiments, but it goes without saying that the present invention is not limited to the specific embodiments exemplified.
本発明は、 (1)イソフラボン類を、前記イソフラボン類をアグリコンに変換する酵素で処理する工程、
(2)前記工程(1)で得られた前記アグリコンを含有する培地で嫌気性微生物を培養し、前記嫌気性微生物により、前記アグリコンをエクオールに変換する工程、及び、
(3)前記工程(2)で産生された前記エクオールを含有するエクオール含有組成物を、前記培地から回収する工程、
を含む、エクオール含有組成物の製造方法、に関する。
The present invention relates to (1) a step of treating isoflavones with an enzyme that converts the isoflavones into aglycones.
(2) A step of culturing an anaerobic microorganism in a medium containing the aglycone obtained in the step (1), and converting the aglycone into equol by the anaerobic microorganism, and a step of converting the aglycone into equol.
(3) A step of recovering the equol-containing composition containing the equol produced in the step (2) from the medium.
The present invention relates to a method for producing an equol-containing composition.
本発明に係るエクオール含有組成物の製造方法は、(1)イソフラボン類を、前記イソフラボン類をアグリコンに変換する酵素で処理する「酵素処理工程」、(2)前記工程(1)で得られた前記アグリコンを含有する培地で嫌気性微生物を培養し、前記嫌気性微生物により、前記アグリコンをエクオールに変換する「発酵工程」、及び、(3)前記工程(2)で産生された前記エクオールを含有するエクオール含有組成物を、前記培地から回収する「回収工程」を含む。 The method for producing an equol-containing composition according to the present invention was obtained in (1) an "enzyme treatment step" in which isoflavones are treated with an enzyme that converts the isoflavones into aglycone, and (2) the step (1). An "fermentation step" in which an anaerobic microorganism is cultured in a medium containing the aglycone and the aglycone is converted into equol by the anaerobic microorganism, and (3) contains the equol produced in the step (2). Includes a "recovery step" of recovering the equol-containing composition to be recovered from the medium.
なお、本発明に係るエクオール含有組成物の製造方法は、上記(1)~(3)の工程を有するものであるが、その他の工程を有していてもよい。
その他の工程としては、例えば、後述する酵素処理工程において酵素処理の基質となるイソフラボン類を調製するに際し、大豆、クズ、レッドクローバー、カンゾウなどのマメ科植物を粉砕、抽出、樹脂精製などにより調製する工程が挙げられる。例えば、特開平11-263786号公報に開示されている大豆胚芽を原料としたイソフラボン化合物の製造方法のように、従来の方法により行うことができる。該工程は後述する酵素処理工程の前に行うことができる。
The method for producing an equol-containing composition according to the present invention has the steps (1) to (3) above, but may have other steps.
As another step, for example, when preparing isoflavones as a substrate for enzyme treatment in the enzyme treatment step described later, legumes such as soybean, kudzu, red clover, and licorice are prepared by crushing, extracting, and resin purification. Steps to be taken. For example, it can be carried out by a conventional method as in the method for producing an isoflavone compound using soybean germ as a raw material disclosed in JP-A-11-263786. The step can be performed before the enzyme treatment step described later.
<1.酵素処理工程>
本発明の酵素処理工程は、イソフラボン類を、該イソフラボン類をアグリコンに変換する酵素で処理する工程である。
<1. Enzyme treatment process>
The enzyme treatment step of the present invention is a step of treating isoflavones with an enzyme that converts the isoflavones into aglycone.
<1-1.イソフラボン類>
本発明のイソフラボン類は、イソフラボンを基本骨格とするフラボノイドの配糖体である。その原料に特に制限はないが、例えば、大豆、クズ、レッドクローバー、カンゾウなどマメ科植物から得ることができる。これらの中でも、アグリコンとしてダイゼインの含有量の多い大豆が好ましく、その中でも大豆胚軸がより好ましい。
<1-1. Isoflavones>
The isoflavones of the present invention are glycosides of flavonoids having isoflavones as a basic skeleton. The raw material is not particularly limited, but can be obtained from legumes such as soybean, kudzu, red clover, and licorice. Among these, soybean having a high content of daidzein as an aglycone is preferable, and among them, soybean hypocotyl is more preferable.
本発明のイソフラボン類は、特段限定されないが、アグリコンのアセチル化配糖体、アグリコンのマロニル化配糖体、及びアグリコンのスクシニル化配糖体等の任意の誘導体を挙げることができる。
アグリコンの配糖体としては、例えば、ダイジンなどを挙げることができる。アグリコンのアセチル化配糖体としては、アセチルダイジンなどを挙げることができる。アグリコンのマロニル化配糖体としては、マロニルダイジンなどを挙げることができる。アグリコンのスクシニル化配糖体としては、スクシニルダイジンなどを挙げることができる。
本発明のイソフラボン類には、これらの一種が含まれていてもよく、複数種含まれてい
てもよい。これらの中でも、ダイジンが好ましい。
なお、本明細書において、イソフラボン類とは、アグリコンに糖が結合した上記配糖体等の任意の誘導体を指すものとし、糖が結合していない、すなわちアグリコン自体は含まれないものとする。
The isoflavones of the present invention are not particularly limited, and examples thereof include any derivative such as an acetylated glycoside of aglycone, a malonylated glycoside of aglycone, and a succinylated glycoside of aglycone.
Examples of glycosides of aglycone include daidzin and the like. Examples of the acetylated glycoside of aglycone include acetyldaidzin. Examples of the malonylated glycoside of aglycone include malonyl daidzin. Examples of the succinylated glycoside of aglycone include succinyl-daidzin.
The isoflavones of the present invention may contain one of these, or may contain a plurality of them. Among these, Daijin is preferable.
In the present specification, isoflavones refer to any derivative such as the above-mentioned glycoside in which sugar is bound to aglycone, and sugar is not bound, that is, aglycone itself is not included.
本発明の酵素処理工程で用いるイソフラボン類は精製されていても、精製されていなくてもよい。大豆胚軸をそのまま用いることもでき、精製されておらず他の成分が含まれていてもよい。市販されているものであれば、例えば、粉砕大豆胚軸(不二製油製)、イソフラボン高含有エキス粉末(タマ生化学株式会社製)などが挙げられる。 The isoflavones used in the enzyme treatment step of the present invention may or may not be purified. The soybean hypocotyl can be used as it is, or it may be unpurified and contain other components. Examples of commercially available products include crushed soybean hypocotyl (manufactured by Fuji Oil Co., Ltd.) and isoflavone-rich extract powder (manufactured by Tama Biochemical Co., Ltd.).
<1-2.アグリコン>
本発明のアグリコンは、特段限定されないが、例えば、ダイゼイン、6-ヒドロキシダイゼイン、ジヒドロダイゼインなどを挙げることができる。
本発明のアグリコンには、これらの一種が含まれていてもよく、複数種含まれていてもよい。これらの中でも、ダイゼインが好ましい。
<1-2. Aglycone >
The aglycone of the present invention is not particularly limited, and examples thereof include daidzein, 6-hydroxydaidzein, and dihydrodaidzein.
The aglycone of the present invention may contain one of these, or may contain a plurality of them. Among these, daidzein is preferable.
<1-3.酵素の種類>
本発明の酵素処理工程におけるイソフラボン類に対して、該イソフラボン類をアグリコンに変換するために作用させる酵素は、上述したアグリコン配糖体等の任意の誘導体において、アグリコンと糖との結合を切断する活性を有していれば、特段限定されないが、エクオール生産の観点から、好ましくは酵素番号がEC3に含まれる酵素、より好ましくはEC3.2に含まれる酵素、さらに好ましくはEC3.2.1に含まれる酵素であり、特に好ましくはβ-グルコシダーゼ(EC 3.2.1.21)、ペクチナーゼ(EC 3.2.1.15)であり、生産性の観点から、最も好ましくはペクチナーゼである。
<1-3. Enzyme type>
The enzyme that acts on the isoflavones in the enzyme treatment step of the present invention to convert the isoflavones into aglycones cleaves the bond between the aglycones and sugars in any derivative such as the above-mentioned aglycone glycoside. As long as it has activity, it is not particularly limited, but from the viewpoint of equol production, the enzyme number is preferably an enzyme contained in EC3, more preferably an enzyme contained in EC3.2, and further preferably EC3.2.1. The contained enzymes are particularly preferably β-glucosidase (EC 3.2.1.21) and pectinase (EC 3.2.1.15), and most preferably pectinase from the viewpoint of productivity.
<1-4.酵素処理>
<1-4-1.イソフラボン類の含有量>
本発明の酵素処理工程において、酵素処理溶液全量に対するイソフラボン類の含有量は、特段限定されないが、エクオールの生産濃度の観点からイソフラボン類として、0.1g/L以上であることが好ましく、0.5g/L以上であることがより好ましく、1.0g/L以上であることがさらに好ましい。一方、酵素活性の観点から、10g/L以下であることが好ましく、5g/L以下であることがより好ましく、3g/L以下であることがさらに好ましい。
<1-4. Enzyme treatment>
<1-4-1. Isoflavone content>
In the enzyme treatment step of the present invention, the content of isoflavones with respect to the total amount of the enzyme treatment solution is not particularly limited, but from the viewpoint of the production concentration of equol, the isoflavones are preferably 0.1 g / L or more, and 0. It is more preferably 5 g / L or more, and further preferably 1.0 g / L or more. On the other hand, from the viewpoint of enzyme activity, it is preferably 10 g / L or less, more preferably 5 g / L or less, and even more preferably 3 g / L or less.
<1-4-2.酵素の濃度>
本発明の酵素処理工程において、酵素処理溶液全量に対する酵素の含有量は、酵素処理が効率良く進行すれば特段限定されないが、酵素として、0.01質量%以上10質量%以下であることが好ましく、0.05質量%以上5%質量以下であることがより好ましく、0.1質量%以上1%質量以下であることがさらに好ましい。
<1-4-2. Enzyme concentration>
In the enzyme treatment step of the present invention, the content of the enzyme with respect to the total amount of the enzyme treatment solution is not particularly limited as long as the enzyme treatment proceeds efficiently, but the enzyme is preferably 0.01% by mass or more and 10% by mass or less. , 0.05% by mass or more and 5% by mass or less, and further preferably 0.1% by mass or more and 1% by mass or less.
<1-4-3.酵素処理温度>
本発明の酵素処理工程において、酵素処理溶液の温度は、酵素活性を保ち、酵素処理が効率良く進行すれば特段限定されないが、酵素を活性化し、迅速な酵素処理を行うために、10℃以上であることが好ましく、30℃以上であることがより好ましく、40℃以上であることがさらに好ましい。一方、酵素活性の保持の観点から、80℃以下であることが好ましく、70℃以下であることがより好ましく、60℃以下であることがさらに好ましい。
<1-4-3. Enzyme treatment temperature>
In the enzyme treatment step of the present invention, the temperature of the enzyme treatment solution is not particularly limited as long as the enzyme activity is maintained and the enzyme treatment proceeds efficiently, but the temperature is 10 ° C. or higher in order to activate the enzyme and perform rapid enzyme treatment. The temperature is preferably 30 ° C. or higher, more preferably 40 ° C. or higher, and even more preferably 40 ° C. or higher. On the other hand, from the viewpoint of maintaining the enzyme activity, it is preferably 80 ° C. or lower, more preferably 70 ° C. or lower, and even more preferably 60 ° C. or lower.
<1-4-4.酵素処理時のpH>
本発明の酵素処理工程において、酵素処理溶液のpHは、酵素活性を保ち、酵素処理が
効率良く進行すれば特段限定されないが、2以上10以下であることが好ましく、3以上8以下であることがより好ましく、4以上7以下であることがさらに好ましい。
<1-4-4. PH during enzyme treatment>
In the enzyme treatment step of the present invention, the pH of the enzyme treatment solution is not particularly limited as long as the enzyme activity is maintained and the enzyme treatment proceeds efficiently, but it is preferably 2 or more and 10 or less, and preferably 3 or more and 8 or less. Is more preferable, and 4 or more and 7 or less are further preferable.
<1-4-5.酵素処理時間>
本発明の酵素処理工程において、酵素処理の時間は、酵素活性を保ち、酵素処理が効率良く進行すれば特段限定されないが、酵素活性の観点から、1時間以上であることが好ましく、4時間以上であることがより好ましく、15時間以上であることがさらに好ましい。一方、生産性の観点から、72時間以下であることが好ましく、48時間以下であることがより好ましく、36時間以下であることがさらに好ましい。
<1-4-5. Enzyme treatment time>
In the enzyme treatment step of the present invention, the enzyme treatment time is not particularly limited as long as the enzyme activity is maintained and the enzyme treatment proceeds efficiently, but from the viewpoint of the enzyme activity, it is preferably 1 hour or more, preferably 4 hours or more. It is more preferable that it is, and it is further preferable that it is 15 hours or more. On the other hand, from the viewpoint of productivity, it is preferably 72 hours or less, more preferably 48 hours or less, and further preferably 36 hours or less.
<2.発酵工程>
本発明の発酵工程は、前記酵素処理工程で得られた前記アグリコンを含有する培地で嫌気性微生物を培養し、前記嫌気性微生物により、前記アグリコンをエクオールに変換する工程である。
なお、上記嫌気性微生物を培養する培地においては、上記酵素処理工程においてイソフラボン類からアグリコンに変化されなかったイソフラボン類をはじめ、その他の成分が含まれていてもよい。
<2. Fermentation process>
The fermentation step of the present invention is a step of culturing an anaerobic microorganism in a medium containing the aglycone obtained in the enzyme treatment step, and converting the aglycone into equol by the anaerobic microorganism.
The medium for culturing the anaerobic microorganism may contain other components such as isoflavones that have not been changed from isoflavones to aglycones in the enzyme treatment step.
<2-1.アグリコン濃度>
本発明の発酵工程におけるアグリコンは、前記酵素処理工程において、イソフラボン類から酵素によって変換されたアグリコンである。
本発明の発酵工程において、該アグリコンの濃度は、特段限定されないが、生産されるエクオールの濃度をより大きくするために、イソフラボン類として、0.1g/L以上であることが好ましく、0.5g/L以上であることがより好ましく、1.0g/L以上であることがさらに好ましい。一方、酵素活性の観点から、10g/L以下であることが好ましく、5g/L以下であることがより好ましく、3g/L以下であることがさらに好ましい。
<2-1. Aglycone concentration>
The aglycone in the fermentation step of the present invention is an aglycone converted from isoflavones by an enzyme in the enzyme treatment step.
In the fermentation step of the present invention, the concentration of the aglycone is not particularly limited, but the isoflavones are preferably 0.1 g / L or more, preferably 0.5 g, in order to further increase the concentration of equol produced. It is more preferably / L or more, and further preferably 1.0 g / L or more. On the other hand, from the viewpoint of enzyme activity, it is preferably 10 g / L or less, more preferably 5 g / L or less, and even more preferably 3 g / L or less.
<2-2.嫌気性微生物>
本発明で用いる嫌気性微生物は、前記アグリコンを含有する培地で培養でき、前記アグリコンからエクオールを発酵できる微生物であれば、特段限定されないが、コーリオバクテリアセアエ(Coriobacteriaceae)科に分類される菌、ストレプトコッカセアエ(Streptococcaceae)科に分類される菌、又はこれらの類縁菌を、エクオール生産能を有するものとして例示することができる。
<2-2. Anaerobic microorganisms>
The anaerobic microorganism used in the present invention is not particularly limited as long as it can be cultivated in a medium containing the aglycone and can ferment equol from the aglycone, but is classified into the family Corioobacteriaceae. , Bacteria classified in the family Streptococcaceae, or related bacteria thereof can be exemplified as having an equol-producing ability.
また、以下の群から選択される属に分類される嫌気性微生物を、エクオール生産能を有するものとして例示することができる。
・コーリオバクテリウム(Coriobacterium)属
・アドレクラウチア(Adlercreutzia)属
・アサッカロバクター(Asaccharobacter)属
・アトポビウム(Atopobium)属
・コリンゼラ(Collinsella)属
・クリプトバクテリウム(Cryptobacterium)属
・デニトロバクテリウム(Denitrobacterium)属
・エガセラ(Eggerthella)属
・エンテロハブダス(Enterorhabdus)属
・ゴードニバクター(Gordonibacter)属
・オルセネラ(Olsenella)属
・パラエゲセエラ(Paraeggerthella)属
・スラッキア(Slackia)属
・ラクトコッカス(Lactococcus)属
In addition, anaerobic microorganisms classified into the genera selected from the following groups can be exemplified as having equol-producing ability.
・ Coriobacterium ・ Adlercreutzia ・ Asaccharobacter ・ Atopobium ・ Collinsella ・ Cryptobacterium ・ Denitrobacterium Genus Denitrobacterium-Genus Eggerthella-Genus Enterorhabdus-Genus Gordonibacter-Genus Olsenella-Genus Paraeggerthella-Genus Slackia-Lactoccus ) Genus
これらの属に分類された微生物から選択され、アグリコンを利用して嫌気発酵によってエクオールを生成する微生物は、本発明における好ましい微生物である。 Microorganisms selected from the microorganisms classified into these genera and producing equol by anaerobic fermentation using aglycone are preferred microorganisms in the present invention.
中でも、上記属に分類された微生物のうち、アサッカロバクター・セラツス(Asaccharobacter celatus)DSM 18785又はそれと近縁である、アサッカロバクター・セラツス(Asaccharobacter celatus)DSM 18785の16S rDNA(16S rRNAの遺伝子配列)と95%以上、好ましくは97%以上、より好ましくは98%以上、さらに好ましくは99%以上の同一性を有する16S rDNAを保有する微生物を使用することが好ましい。アサッカロバクター・セラツス(Asaccharobacter celatus)DSM 18785の16S rRNAの遺伝子配列は配列番号1である。 Among the microorganisms classified into the above genera, 16S rDNA (16S rRNA) of Asaccharobacter celatus DSM 18785 or its closely related microorganisms, Asaccharobacter celatus DSM 18785. It is preferable to use a microorganism having 16S rDNA having an identity of 95% or more, preferably 97% or more, more preferably 98% or more, still more preferably 99% or more with the gene sequence). The gene sequence of 16S rRNA of Asaccharobacter celatus DSM 18785 is SEQ ID NO: 1.
さらに上記微生物のうち、アサッカロバクター(Asaccharobacter)属、スラッキア(Slackia)属、アドレクラウチア(Adlercreutzia)属に属する微生物は、本発明におけるエクオール産生能を有する微生物としてより好ましい。 Further, among the above-mentioned microorganisms, microorganisms belonging to the genus Asaccharobacter, the genus Slackia, and the genus Adlercreutzia are more preferable as the microorganisms having an equol-producing ability in the present invention.
微生物がエクオールを生成することは、培養物中のダイゼイン、ジヒドロダイゼイン、エクオール等を定量することにより確認することができる。これらの定量は、当業者であれば、例えば、WO2012/033150パンフレット、特開2012-135217号公報、特開2012-135218号公報、特開2012-135219号公報などの記載に基づき行うことができる。 The production of equol by microorganisms can be confirmed by quantifying daidzein, dihydrodaidzein, equol and the like in the culture. Those skilled in the art can perform these quantifications based on, for example, the description of WO2012 / 033150 Pamphlet, Japanese Patent Application Laid-Open No. 2012-135217, Japanese Patent Application Laid-Open No. 2012-135218, Japanese Patent Application Laid-Open No. 2012-135219, and the like. ..
さらに、以下の嫌気性微生物を利用することができる。
Adlercreutzia equolifaciens DSM 19450
Enterorhabdus mucosicola DSM 19490
Slackia isoflavoniconvertens HE8(DSM 22006)
Slackia sp. TM-30 FERM P-20729
Eggerthella sp. KCCM-10490
Asaccharobacter celatus DSM 18785
Lactococcus garvieae DSM 6783
Furthermore, the following anaerobic microorganisms can be utilized.
Adlercreutzia equolifaciens DSM 19450
Enterorhabdus mucosicola DSM 19490
Slackia isoflavoniconvertens HE8 (DSM 22006)
Slackia sp. TM-30 FERM P-20729
Eggerthella sp. KCCM-10490
Asaccharobacter celatus DSM 18785
Lactococcus garvieae DSM 6783
上記微生物のうち、アサッカロバクター・セラツス(Asaccharobacter celatus)DSM 18785株、アドレクラウチア・エクオーリファシエンス(Adlercreutzia equolifaciens)DSM 19450株、もしくは、スラッキア・イソフラボニコンバーテンス(Slackia isoflavoniconvertens)DSM 22006株、又はこれらの菌と同様の種としての性質を有する類縁の菌をより好ましい嫌気性微生物として挙げることができる。 Among the above microorganisms, Asaccharobacter celatus DSM 18785 strain, Adlercreutzia equolifaciens DSM 19450 strain, or Slackia isoflavoniconvertens DSM 22006 strain. , Or related bacteria having similar species properties as these bacteria can be mentioned as more preferable anaerobic microorganisms.
上記嫌気性微生物は、その寄託番号に示された寄託機関から入手することができる。各受託番号は、当該嫌気性微生物が、それぞれ次の寄託機関に寄託されていることを示す。
FERM 特許生物寄託センター;International Patent Organism Depositary (IPOD)
http://unit.aist.go.jp/pod/ci/index.html
DSM German Collection of Microorganisms and Cell Cultures (DSMZ)
http://www.dsmz.de/
KCCM Korean Culture Center of Microorganisms
The above anaerobic microorganisms can be obtained from the depositary institution indicated by the deposit number. Each accession number indicates that the anaerobic microorganism has been deposited with the next depository.
FERM International Patent Organism Depositary (IPOD)
http://unit.aist.go.jp/pod/ci/index.html
DSM German Collection of Microorganisms and Cell Cultures (DSMZ)
http://www.dsmz.de/
KCCM Korean Culture Center of Microorganisms
<2-3.培養・発酵条件>
本発明で用いる嫌気性微生物は、エクオールの生産に適した条件で、培地中でアグリコンと接触させられ、培養される。
本発明のエクオール含有組成物の生産に適した条件とは、エクオール生成活性を持つ嫌
気性微生物の生存と活動が維持されることをいう。より具体的には、嫌気性微生物の生存が可能な気相条件(嫌気性条件)が維持され、該嫌気性微生物の活性と増殖を支持するための栄養素が与えられることをいう。嫌気性微生物の生存に適した種々の培地組成が公知である。したがって、先に示したエクオール生産能を有する嫌気性微生物について、当業者は、適切な培地組成を選択することができる。たとえば、実施例において用いた日水製薬社製のGAMブイヨン培地や、Difco社製のBHI培地等を使用することができる。
<2-3. Culture / fermentation conditions>
The anaerobic microorganism used in the present invention is contacted with aglycone in a medium and cultured under conditions suitable for the production of equol.
The conditions suitable for the production of the equol-containing composition of the present invention mean that the survival and activity of anaerobic microorganisms having equol-producing activity are maintained. More specifically, it means that the gas phase condition (anaerobic condition) in which the anaerobic microorganism can survive is maintained, and nutrients for supporting the activity and proliferation of the anaerobic microorganism are provided. Various media compositions suitable for the survival of anaerobic microorganisms are known. Therefore, those skilled in the art can select an appropriate medium composition for the above-mentioned anaerobic microorganisms having an equol-producing ability. For example, the GAM bouillon medium manufactured by Nissui Pharmaceutical Co., Ltd., the BHI medium manufactured by Difco, etc. used in the examples can be used.
本発明で用いられる培地には、例えば、水溶性の有機物を炭素源として加えることができる。水溶性の有機物として、ソルボース、フラクトース、グルコース、並びに、吉草酸、酪酸、プロピオン酸、酢酸、及びギ酸など有機酸類等の化合物を挙げることができる。 For example, a water-soluble organic substance can be added to the medium used in the present invention as a carbon source. Examples of water-soluble organic substances include sorbose, fructose, glucose, and compounds such as arboric acid, butyric acid, propionic acid, acetic acid, and organic acids such as formic acid.
炭素源としての培地に加える有機物の濃度は、効率的に培地中の嫌気性微生物を発育させるために適宜調節することができる。一般的には、0.1~10wt/vol%の範囲から添加量を選択することによって、過不足を避けることができる。 The concentration of organic matter added to the medium as a carbon source can be appropriately adjusted in order to efficiently grow anaerobic microorganisms in the medium. Generally, excess or deficiency can be avoided by selecting the addition amount from the range of 0.1 to 10 wt / vol%.
上記の炭素源に加えて、培地には、窒素源を加えることができる。本発明において、窒素原としては通常の発酵に用いうる各種の窒素化合物を用いることができる。好ましい無機窒素源は、アンモニウム塩、及び硝酸塩である。好ましい有機窒素源はアミノ酸類、酵母エキス、ペプトン類、肉エキス、肝臓エキス、消化血清末などである。より好ましい無機窒素源は、硫安、塩化アンモニウム、リン酸アンモニウム、リン酸水素アンモニウム、硝酸カリウム及び硝酸ソーダである。より好ましい窒素源はアルギニン、シトルリン、オルニチン、リジン、酵母エキス、ペプトン類である。 In addition to the above carbon sources, nitrogen sources can be added to the medium. In the present invention, various nitrogen compounds that can be used for ordinary fermentation can be used as the nitrogen source. Preferred inorganic nitrogen sources are ammonium salts and nitrates. Preferred organic nitrogen sources are amino acids, yeast extracts, peptones, meat extracts, liver extracts, digested serum powder and the like. More preferred sources of inorganic nitrogen are ammonium sulfate, ammonium chloride, ammonium phosphate, ammonium hydrogen phosphate, potassium nitrate and sodium nitrate. More preferred nitrogen sources are arginine, citrulline, ornithine, lysine, yeast extract and peptones.
更に、炭素源や窒素源に加えて、偏性嫌気性微生物の培養に適した他の有機物あるいは無機物を培地に加えることもできる。例えば、ビタミンなどの補因子や各種の塩類等の無機化合物を培地に加えることによって、偏性嫌気性微生物の増殖や活性を増強できる場合もある。例えば、無機化合物、ビタミン類、動植物由来の微生物増殖補助因子として以下のものを挙げることができる。 Further, in addition to carbon sources and nitrogen sources, other organic or inorganic substances suitable for culturing obligate anaerobic microorganisms can be added to the medium. For example, the growth and activity of obligate anaerobic microorganisms may be enhanced by adding cofactors such as vitamins and inorganic compounds such as various salts to the medium. For example, the following can be mentioned as microbial growth cofactors derived from inorganic compounds, vitamins, animals and plants.
無機化合物として、例えば、リン酸二水素カリウム、硫酸マグネシウム、硫酸マンガン、塩化ナトリウム、塩化コバルト、塩化カルシウム、硫酸亜鉛、硫酸銅、明ばん、モリブデン酸ソーダ、塩化カリウム、ホウ酸等、塩化ニッケル、タングステン酸ナトリウム、セレン酸ナトリウム、硫酸第一鉄アンモニウムが挙げられる。 Examples of the inorganic compound include potassium dihydrogen phosphate, magnesium sulfate, manganese sulfate, sodium chloride, cobalt chloride, calcium chloride, zinc sulfate, copper sulfate, amber, sodium molybdenate, potassium chloride, boric acid and the like, nickel chloride, etc. Examples thereof include sodium tungstate, sodium selenate, and ammonium ferrous sulfate.
また、ビタミン類として、例えば、ビオチン、葉酸、ピリドキシン、チアミン、リボフラビン、ニコチン酸、パントテン酸、ビタミンB12、チオオクト酸、p-アミノ安息香酸が挙げられる。さらに、ポルフィリン化合物であるヘミンを添加するとよい場合がある。 Examples of vitamins include biotin, folic acid, pyridoxine, thiamine, riboflavin, nicotinic acid, pantothenic acid, vitamin B12, thiooctonic acid, and p-aminobenzoic acid. In addition, it may be advisable to add hemin, which is a porphyrin compound.
これらの無機化合物やビタミン類、あるいは増殖補助因子を添加して培養液を製造する方法は公知である。培地は、液体、半固体、あるいは固体とすることができる。本発明のエクオールの製造方法において、好ましい培地の形態は、液体培地である。 A method for producing a culture solution by adding these inorganic compounds, vitamins, or growth support factors is known. The medium can be liquid, semi-solid, or solid. In the method for producing equol of the present invention, the preferred medium form is a liquid medium.
本発明で用いる嫌気性微生物は、公知の微生物の培養方法にしたがって培養することができる。工業的な製造には、培地や基質ガスを連続的に供給することができ、かつ培養物を回収するための機構を備えた連続培養システム(continuous fermentation system)が好適である。 The anaerobic microorganism used in the present invention can be cultured according to a known method for culturing a microorganism. For industrial production, a continuous culture system (continuus fermentation system) capable of continuously supplying a medium or a substrate gas and having a mechanism for recovering a culture is suitable.
本発明で用いる嫌気性微生物の培養においては、連続培養システム内への酸素の混入を
防ぐことが必要である。培養器は通常用いられる培養槽がそのまま利用できる。嫌気性微生物の培養にも利用することができる培養タンクは市販されている。培養槽内に混入する酸素を、窒素などの不活性気体あるいは水素ガスなどで置換することにより、嫌気的な雰囲気を作ることができる。
In culturing anaerobic microorganisms used in the present invention, it is necessary to prevent oxygen from being mixed into the continuous culture system. As the incubator, the normally used culture tank can be used as it is. Culture tanks that can also be used for culturing anaerobic microorganisms are commercially available. An anaerobic atmosphere can be created by substituting the oxygen mixed in the culture tank with an inert gas such as nitrogen or hydrogen gas.
例えば、嫌気培養ジャー(anaerobic jar)を、嫌気性微生物を培養するためのバイオリアクターとすることができる。嫌気培養ジャーは、金属、ガラス、あるいは合成樹脂製の気密容器で構成され、内部を大気中の酸素から遮断することができる。さらに、嫌気培養ジャーは、嫌気培養ジャー内部の空間や培養液中に含まれる分子状酸素を除去するための機構を備えることができる。たとえば、嫌気培養ジャー内部を吸引する真空ポンプを接続して吸引し、酸素以外の気体を供給することで、内部を嫌気状態に維持することができる。 For example, an anaerobic jar can be a bioreactor for culturing anaerobic microorganisms. The anaerobic culture jar is composed of an airtight container made of metal, glass, or synthetic resin, and can shield the inside from oxygen in the atmosphere. Further, the anaerobic culture jar can be provided with a mechanism for removing molecular oxygen contained in the space inside the anaerobic culture jar and the culture solution. For example, the inside can be maintained in an anaerobic state by connecting and sucking a vacuum pump that sucks the inside of the anaerobic culture jar and supplying a gas other than oxygen.
本発明においては、培養槽に付加的な機能を与えることができる。たとえば、通常使用される撹はん混合槽のほか、気泡塔型、ドラフトチューブ型の培養槽も利用できる。液体培地に吹き込まれる混合気体によって微生物は遊離分散され、微生物と培地を十分に接触させることができる。また、バイオトリックリングフィルター(biotrickling filter)のように通気性の高いスラグ、その他セラミック系の無機充てん物、あるいはポリプロピレン等の有機合成物質の充てん層に、水分を滴らせながら微生物を生息させ、そこにガスを通気しながら培養することもできる。さらに、使用する微生物は常法によりカラギーナンゲル、アルギン酸ゲル、アクリルアミドゲル、キチン、セルロース、寒天などに固定化して用いることもできる。 In the present invention, the culture tank can be provided with an additional function. For example, in addition to the normally used stirring and stirring mixing tank, a bubble tower type and draft tube type culture tank can also be used. The mixed gas blown into the liquid medium allows the microorganisms to be free-dispersed and sufficiently contact the microorganisms with the medium. In addition, microorganisms are allowed to inhabit the packed layer of highly breathable slag such as biotricling filter, other ceramic-based inorganic packed materials, or organic synthetic substances such as polypropylene while dripping water. It is also possible to incubate while aerating gas there. Further, the microorganism to be used can be immobilized on carrageenan gel, alginate gel, acrylamide gel, chitin, cellulose, agar and the like by a conventional method.
本発明の発酵工程においては、上記の基質ガスからなる気相を構成する気体の組み合わせは特に制限されるものではなく、水素、二酸化炭素、窒素等から選択される1種類以上の気体を構成成分として用いることが可能である。当該気相においては、水素が構成成分として含まれていることが好ましい。 In the fermentation step of the present invention, the combination of gases constituting the gas phase composed of the above-mentioned substrate gas is not particularly limited, and one or more kinds of gases selected from hydrogen, carbon dioxide, nitrogen and the like are constituent components. Can be used as. In the gas phase, hydrogen is preferably contained as a constituent component.
上記の場合、当該発酵工程の気相において、水素の分圧パーセント濃度が2~100%であることが好ましい。たとえば、2%、4%、6%、10%、20%、30%、40%、50%、80%、100%、又はこれらから選択される2点の分圧パーセント濃度を下限(「~以上、又は、~より高い)及び上限(~以下、又は、~より低い)、とする濃度範囲により示される分圧パーセント濃度であることが好ましい。 In the above case, it is preferable that the partial pressure percent concentration of hydrogen is 2 to 100% in the gas phase of the fermentation step. For example, the lower limit is 2%, 4%, 6%, 10%, 20%, 30%, 40%, 50%, 80%, 100%, or the partial pressure percent concentration at two points selected from these ("~". It is preferable that the concentration is a partial pressure percent concentration indicated by the concentration range of the above or higher (or higher) and the upper limit (or lower or lower).
また、効率よくエクオールを生成させるためには、気相を構成する混合気体の培養槽への通気量は0.01~2.0 V/V/Mガス量/液量/分であることが好ましい。 Further, in order to efficiently generate equol, the aeration amount of the mixed gas constituting the gas phase to the culture tank should be 0.01 to 2.0 V / V / M gas amount / liquid amount / minute. preferable.
本発明で用いる嫌気性微生物は、通常、37℃付近(30~42℃)の温度でエクオール生産能を有する嫌気性微生物である。 The anaerobic microorganism used in the present invention is usually an anaerobic microorganism having an equol-producing ability at a temperature of around 37 ° C. (30 to 42 ° C.).
本発明において、嫌気性微生物を培養する際の加圧条件は、当該微生物が生育できる条件であれば特に限定されるものではないが、好ましい加圧条件としては、0.02~0.2MPaの範囲を挙げることができる。 In the present invention, the pressurizing condition for culturing an anaerobic microorganism is not particularly limited as long as the microorganism can grow, but a preferable pressurizing condition is 0.02 to 0.2 MPa. The range can be raised.
微生物の十分な生育のため、培養物のpHは、3.0~8.0が好ましく、4.5~7.5がより好ましい。また、エクオールの回収量を増加させるため、培養槽の温度は特に制限されるものではないが、37℃を好ましい温度として挙げることができる。 For sufficient growth of microorganisms, the pH of the culture is preferably 3.0 to 8.0, more preferably 4.5 to 7.5. Further, in order to increase the amount of equol recovered, the temperature of the culture tank is not particularly limited, but 37 ° C. can be mentioned as a preferable temperature.
<3.回収工程>
本発明の回収工程は、前記発酵工程で産生された前記エクオールを含有するエクオール
含有組成物を、前記培地から回収する工程である。
<3. Collection process>
The recovery step of the present invention is a step of recovering the equol-containing composition containing the equol produced in the fermentation step from the medium.
当業者は、生成した嫌気性微生物と培養生成液を分離するために公知の任意の方法を用いることができる。好ましい分離の方法は、ろ過性能、濃縮性能を有するホローファイバー型限外ろ過あるいは精密ろ過膜を利用する方法である。また、微生物と該生成液の分離に十分なろ過速度を得るためには使用する微生物に応じて適当な分画分子量の膜を選択すればよい。生産されたエクオールは当業者に公知の任意の手段で培地から回収することができる。例えば、培養槽から限外ろ過膜を通して分離された培養液からエクオールを回収することができる。エクオールの精製方法は公知である。たとえば、培養物を遠心分離などで菌体を除き、上清を減圧下に濃縮、乾固後、70%エタノールあるいはメタノールで抽出する。抽出液をさらにシリカゲルクロマトグラフィーや晶析などの操作を行うことで精製できる。また、アンバーライトやセパビーズなどスチレン-ジビニルベンゼンの吸着樹脂も用いることができる。 One of ordinary skill in the art can use any known method for separating the produced anaerobic microorganism and the culture product. A preferred separation method is a method using a hollow fiber type ultrafiltration membrane or a microfiltration membrane having filtration performance and concentration performance. Further, in order to obtain a filtration rate sufficient for separating the microorganism and the product solution, a membrane having an appropriate molecular weight cut-off may be selected according to the microorganism to be used. The produced equol can be recovered from the medium by any means known to those skilled in the art. For example, equol can be recovered from the culture broth separated from the culture tank through an ultrafiltration membrane. Equol purification methods are known. For example, the cells are removed by centrifugation or the like, the supernatant is concentrated under reduced pressure, dried, and then extracted with 70% ethanol or methanol. The extract can be further purified by performing operations such as silica gel chromatography and crystallization. Further, a styrene-divinylbenzene adsorption resin such as amber light or sepa beads can also be used.
本発明の回収工程では、効率よくエクオールを回収するため、培養槽に供給される新鮮な培地の量は、培養槽内の培養物における希釈率が時間当たり0.04~2/hrが好ましい。より好ましい希釈率は0.08~1/hrである。 In the recovery step of the present invention, in order to efficiently recover equol, the amount of fresh medium supplied to the culture tank is preferably 0.04 to 2 / hr per hour in the culture in the culture tank. A more preferable dilution ratio is 0.08 to 1 / hr.
<4.エクオール含有組成物>
本発明の製造方法により得られるエクオール含有組成物は、様々な用途、例えば、化粧料や医薬品、食品などとして提供することができる。飲食品又は医薬品等として摂取することにより、乳癌、前立腺癌、骨粗しょう症、高コレステロール血症、心疾患、更年期障害等を予防できる。
<4. Equol-containing composition>
The equol-containing composition obtained by the production method of the present invention can be provided for various purposes such as cosmetics, pharmaceuticals, foods and the like. By ingesting it as a food or drink or a drug, breast cancer, prostate cancer, osteoporosis, hypercholesterolemia, heart disease, menopausal disorders, etc. can be prevented.
<5.化粧料>
本発明のエクオール含有組成物を化粧料の素材として用いる場合、該エクオール含有組成物を水溶液、ローション、スプレー液、懸濁液および乳化液などの液状;粉末、顆粒およびブロック状などの固体状;クリームおよびペーストなどの半固体状;ゲル状等の各種所望の剤形の化粧料に調製することができる。このような化粧料は、洗顔料、乳液、クリーム、ゲル、エッセンス(美容液)、パック・マスク等の基礎化粧料、ファンデーション、口紅等のメーキャップ化粧料、口腔化粧料、芳香化粧料、毛髪化粧料、ボディ化粧料等の各種化粧料として有用である。本発明により得られるエクオールを含有組成物を含む化粧料は、美白用化粧料、ニキビ改善用化粧料、しわ改善化粧料として使用される。
本発明のエクオール含有組成物を含有する化粧料は、常法に従って製造することができる。また、化粧料への配合量、配合方法、配合時期は適宜選択することができる。さらに、必要に応じて、瓶、袋、缶、スプレー缶、噴霧容器、箱、パック等の適宜の容器に封入することができる。
本発明のエクオール含有組成物を化粧料の素材として用いる場合、化粧料全量に対する上記エクオール含有組成物の含有量は、本発明の所望の効果が奏される限り特に限定されないが、エクオールとして、通常0.00005~10質量%であり、好ましくは0.0001~5質量%であり、より好ましくは0.0001~2質量%である。
<5. Cosmetics>
When the equol-containing composition of the present invention is used as a material for cosmetics, the equol-containing composition is used in liquid form such as aqueous solution, lotion, spray solution, suspension and emulsion; solid form such as powder, granule and block form; Semi-solid forms such as creams and pastes; can be prepared into various desired dosage forms of cosmetics such as gels. Such cosmetics include basic cosmetics such as washing pigments, milky lotions, creams, gels, essences (beauty essences), packs and masks, makeup cosmetics such as foundations and lipsticks, oral cosmetics, aromatic cosmetics, and hair cosmetics. It is useful as various cosmetics such as cosmetics and body cosmetics. The cosmetic containing the equol-containing composition obtained by the present invention is used as a whitening cosmetic, an acne improving cosmetic, and a wrinkle improving cosmetic.
The cosmetic containing the equol-containing composition of the present invention can be produced according to a conventional method. In addition, the blending amount, blending method, and blending time in the cosmetic can be appropriately selected. Further, if necessary, it can be enclosed in an appropriate container such as a bottle, a bag, a can, a spray can, a spray container, a box, or a pack.
When the equol-containing composition of the present invention is used as a material for cosmetics, the content of the equol-containing composition with respect to the total amount of cosmetics is not particularly limited as long as the desired effect of the present invention is exhibited, but as equol, it is usually used. It is 0.00005 to 10% by mass, preferably 0.0001 to 5% by mass, and more preferably 0.0001 to 2% by mass.
<6.医薬品>
本発明のエクオール含有組成物を医薬品の素材として用いる場合、その剤形は、予防または治療しようとする疾患や医薬品の使用形態、投与経路等に応じて選択することができる。例えば、錠剤、被覆錠剤、丸剤、カプセル剤、顆粒剤、散剤、液剤、懸濁剤、乳剤、シロップ剤、注射剤、坐剤、浸剤、煎剤、チンキ剤等が挙げられる。これらの各種製剤は、常法に従って主薬に対して必要に応じて充填剤、増量剤、賦形剤、結合剤、保湿剤、崩壊剤、界面活性剤、滑沢剤、着色剤、矯味矯臭剤、溶解補助剤、懸濁剤、コーティング剤などの医薬の製剤技術分野において通常使用し得る既知の補助剤を用いて製剤化することができる。また、この医薬製剤中に着色剤、保存剤、香料、風味剤、甘味剤等や他の医薬品を含有させてもよい。
本発明のエクオール含有組成物は、乳癌、前立腺癌、骨粗しょう症、心疾患、更年期障害の予防や治療のために使用することができる。
<6. Pharmaceuticals>
When the equol-containing composition of the present invention is used as a material for a pharmaceutical product, the dosage form thereof can be selected according to the disease to be prevented or treated, the form of use of the pharmaceutical product, the route of administration, and the like. Examples thereof include tablets, coated tablets, pills, capsules, granules, powders, liquids, suspensions, emulsions, syrups, injections, suppositories, dipping agents, decoctions, tinctures and the like. These various formulations are prepared according to the conventional method for fillers, bulking agents, excipients, binders, moisturizers, disintegrants, surfactants, lubricants, colorants, and flavoring agents as needed. , Dissolving aids, suspending agents, coating agents and the like, which can be formulated using known excipients commonly used in the pharmaceutical formulation technology field. In addition, a coloring agent, a preservative, a flavoring agent, a flavoring agent, a sweetening agent, or other pharmaceutical products may be contained in this pharmaceutical product.
The equol-containing composition of the present invention can be used for the prevention and treatment of breast cancer, prostate cancer, osteoporosis, heart disease and menopausal disorders.
本発明のエクオール含有組成物を医薬品の素材として用いる場合、医薬品全量に対する上記エクオール含有組成物の含有量は、本発明の所望の効果が奏される限り特に限定されないが、エクオールとして、通常0.001~30質量%であり、好ましくは0.01~20質量%であり、より好ましくは0.1~10質量%である。また、上記エクオール含有組成物を含有する医薬品の投与量は、患者の年齢、体重、症状の程度等によって適宜設定され得る。 When the equol-containing composition of the present invention is used as a material for a pharmaceutical product, the content of the equol-containing composition with respect to the total amount of the pharmaceutical product is not particularly limited as long as the desired effect of the present invention is exhibited, but as equol, it is usually 0. It is 001 to 30% by mass, preferably 0.01 to 20% by mass, and more preferably 0.1 to 10% by mass. In addition, the dose of the drug containing the equol-containing composition can be appropriately set depending on the age, body weight, degree of symptoms, and the like of the patient.
<7.食品>
本発明のエクオール含有組成物を食品の素材として用いる場合、一般の食品の他、特定保健用食品、栄養補助食品、機能性食品、病者用食品、食品添加物等として使用できる。食品の形態としては、本発明に係るエクオール含有組成物を含む清涼飲料、ミルク、プリン、ゼリー、飴、ガム、グミ、ヨーグルト、チョコレート、スープ、クッキー、スナック菓子、アイスクリーム、アイスキャンデー、パン、ケーキ、シュークリーム、ハム、ミートソース、カレー、シチュー、チーズ、バター、ドレッシング等を例示することができる。
<7. Food >
When the equol-containing composition of the present invention is used as a food material, it can be used as a food for specified health use, a dietary supplement, a functional food, a food for the sick, a food additive, and the like, in addition to general foods. As food forms, soft drinks containing the equol-containing composition according to the present invention, milk, pudding, jelly, candy, gum, gummies, yogurt, chocolate, soup, cookies, snacks, ice cream, ice candy, bread, cake. , Cream puff, ham, meat sauce, curry, stew, cheese, butter, dressing and the like can be exemplified.
本発明のエクオール含有組成物は、水、タンパク質、糖質、脂質、ビタミン類、ミネラル類、有機酸、有機塩基、果汁、フレーバー類等を主成分として使用することができる。タンパク質としては、例えば、全脂粉乳、脱脂粉乳、部分脱脂粉乳、カゼイン、大豆タンパク質、鶏卵タンパク質、肉タンパク質等の動植物性タンパク質、及びこれらの加水分解物、バターなどが挙げられる。糖質としては、糖類、加工澱粉(デキストリンのほか、可溶性澱粉、ブリティッシュスターチ、酸化澱粉、澱粉エステル、澱粉エーテル等)、食物繊維などが挙げられる。脂質としては、例えば、ラード、サフラワー油、コーン油、ナタネ油、ヤシ油、これらの分別油、水素添加油、エステル交換油等の植物性油脂などが挙げられる。ビタミン類としては、例えば、ビタミンA、カロチン類、ビタミンB群、ビタミンC、ビタミンD群、ビタミンE、ビタミンK群、ビタミンP、ビタミンQ、ナイアシン、ニコチン酸、パントテン酸、ビオチン、イノシトール、コリン、葉酸などが挙げられ、ミネラル類としては、例えば、カルシウム、カリウム、マグネシウム、ナトリウム、銅、鉄、マンガン、亜鉛、セレン、乳清ミネラルなどが挙げられる。有機酸としては、例えば、リンゴ酸、クエン酸、乳酸、酒石酸などが挙げられる。これらの成分は、2種以上を組み合わせて使用してもよく、合成品及び/又はこれらを多く含む食品を用いてもよい。 The equol-containing composition of the present invention can contain water, proteins, sugars, lipids, vitamins, minerals, organic acids, organic bases, fruit juices, flavors and the like as main components. Examples of the protein include animal and vegetable proteins such as full fat powder, skim milk powder, partially skim milk powder, casein, soybean protein, chicken egg protein, meat protein, and hydrolyzates and butters thereof. Examples of carbohydrates include sugars, processed starches (dextrins, soluble starches, British starch, oxidized starches, starch esters, starch ethers, etc.), dietary fibers and the like. Examples of the lipid include lard, safflower oil, corn oil, rapeseed oil, coconut oil, fractionated oils thereof, hydrogenated oil, and vegetable fats and oils such as ester exchange oil. Examples of vitamins include vitamin A, carotene, vitamin B group, vitamin C, vitamin D group, vitamin E, vitamin K group, vitamin P, vitamin Q, niacin, nicotinic acid, pantothenic acid, biotin, inositol, and choline. , Folic acid and the like, and examples of minerals include calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, selenium and milky minerals. Examples of the organic acid include malic acid, citric acid, lactic acid, tartaric acid and the like. These ingredients may be used in combination of two or more, and synthetic products and / or foods containing a large amount thereof may be used.
本発明のエクオール含有組成物を含有する食品は、常法に従って製造することができる。また、食品への配合量、配合方法、配合時期は適宜選択することができる。さらに、必要に応じて、瓶、袋、缶、箱、パック等の適宜の容器に封入することができる。
本発明のエクオール含有組成物を食品の素材として用いる場合、食品全量に対する上記エクオール含有組成物の含有量は、本発明の所望の効果が奏される限り特に限定されないが、エクオールとして、通常0.01~10質量%であり、好ましくは0.05~5質量%であり、より好ましくは0.1~2質量%である。
The food containing the equol-containing composition of the present invention can be produced according to a conventional method. In addition, the amount to be blended in the food, the blending method, and the blending time can be appropriately selected. Further, if necessary, it can be enclosed in an appropriate container such as a bottle, a bag, a can, a box, or a pack.
When the equol-containing composition of the present invention is used as a material for food, the content of the equol-containing composition with respect to the total amount of food is not particularly limited as long as the desired effect of the present invention is obtained, but as equol, it is usually 0. It is 01 to 10% by mass, preferably 0.05 to 5% by mass, and more preferably 0.1 to 2% by mass.
以下、具体的な実施例により本発明をさらに詳細に説明するが、本発明はこれらの実施例に限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to specific examples, but the present invention is not limited to these examples.
[実施例1]
<1.イソフラボン類の調製>
本実施例では、イソフラボン類として、大豆胚軸(不二製油製)をワーリングブレンダーを用いて、1分間×3回(計3分間)、粉砕したものを用いた。
[Example 1]
<1. Preparation of isoflavones>
In this example, as isoflavones, soybean hypocotyls (manufactured by Fuji Oil Co., Ltd.) were crushed using a Waring blender for 1 minute x 3 times (3 minutes in total).
<2.酵素処理>
酵素処理溶液としては、イソフラボン類として270gの大豆胚軸(不二製油製)、酵素として2.7gのペクチナーゼGアマノ、および1180gの脱イオン水を用いて、計1450gとし、pHを4~7に調整して調製した。酵素処理は、50℃で20~24時間、撹拌しながら行った。
<2. Enzyme treatment>
As the enzyme treatment solution, 270 g of soybean hypocotyl (manufactured by Fuji Oil) as isoflavones, 2.7 g of pectinase G Amano as an enzyme, and 1180 g of deionized water were used to make a total of 1450 g and the pH was 4 to 7. It was prepared by adjusting to. The enzyme treatment was carried out at 50 ° C. for 20 to 24 hours with stirring.
<3.嫌気性微生物による発酵>
(種培養)
GAMブイヨン培地(日水製薬製)5.9gとL-アルギニン塩酸塩1.2gを純水100mLに溶かし、窒素ガスを通じながら20mLずつ嫌気性菌培養用18mm試験管(三紳工業製)に分注し、ブチルゴム栓、プラスチックキャップをして115℃、15分間滅菌した。
この培地に-80℃で凍結保存していたアサッカロバクター・セラツス(Asaccharobacter celatus) DSM 18785株を植菌し、無菌フィルターを通した水素ガスで気相を2分間
以上置換した後、37℃、250spmで16時間振とう培養を行った。
<3. Fermentation by anaerobic microorganisms>
(Seed culture)
Dissolve 5.9 g of GAM bouillon medium (manufactured by Nissui Pharmaceutical Co., Ltd.) and 1.2 g of L-arginine hydrochloride in 100 mL of pure water, and divide 20 mL each into 18 mm test tubes (manufactured by Sanshin Kogyo) for culturing anaerobic bacteria while passing nitrogen gas. It was poured, covered with a butyl rubber stopper and a plastic cap, and sterilized at 115 ° C. for 15 minutes.
Asaccharobacter celatus DSM 18785 strain, which had been cryopreserved at -80 ° C, was inoculated into this medium, the gas phase was replaced with hydrogen gas through a sterile filter for 2 minutes or more, and then 37 ° C. , 250 spm for 16 hours shaking culture.
(発酵)
上記種培養液と同様に、L-アルギニン塩酸塩を添加したGAMブイヨン培地を、115℃、15分間オートクレーブ滅菌し、室温まで冷却後、上述した種培養液を植菌し、気相を水素ガスで無菌的に2分間以上置換した後、37℃、250spmの条件で振とう培養し、発酵を行った。
(fermentation)
Similar to the above seed culture medium, the GAM bouillon medium supplemented with L-arginine hydrochloride was autoclaved at 115 ° C. for 15 minutes, cooled to room temperature, then inoculated with the above-mentioned seed culture medium, and the gas phase was hydrogen gas. After aseptically substituting for 2 minutes or more, the cells were shake-cultured at 37 ° C. and 250 spm and fermented.
<4.エクオール含有組成物の回収>
上記発酵後の培養液を3000rpmで10分遠心し、0.45μmのMF膜でろ過し、不溶物を除去して、エクオール含有組成液を回収した。組成液を乾燥処理(スプレードライ処理)することによりエクオール含有物(EQ-N)を得た。
<4. Recovery of equol-containing compositions>
The culture solution after fermentation was centrifuged at 3000 rpm for 10 minutes and filtered through a 0.45 μm MF membrane to remove insoluble matters, and the equol-containing composition solution was recovered. The composition liquid was dried (spray-dried) to obtain an equol-containing substance (EQ-N).
<5.アレルゲンの検出>
得られたエクオール含有組成物について、FASTKITスリム大豆(日本ハム中央研究所製
)を用いてアレルゲンの検出を行った。
具体的な方法は、FATKITスリムのマニュアルに従った。サンプルとしてEQ-N 2gを使用し、キット中の抽出用緩衝液38mLを加え、30~60分混合後、3回抽出し、その後、3000×g、4℃、20分で遠心分離後し、上清をろ紙でろ過し、キット内の希釈用緩衝液で10倍に希釈し測定サンプルとした。測定は、テストストリップに100μLを滴下し、15分展開後目視判定をした。
<5. Allergen detection>
Allergens were detected in the obtained equol-containing composition using FASTKIT slim soybean (manufactured by Nippon Ham Central Research Institute).
The specific method was according to the FATKIT Slim manual. Using 2 g of EQ-N as a sample, add 38 mL of the extraction buffer in the kit, mix for 30 to 60 minutes, extract 3 times, and then centrifuge at 3000 xg, 4 ° C, 20 minutes. The supernatant was filtered through filter paper and diluted 10-fold with the dilution buffer in the kit to prepare a measurement sample. For the measurement, 100 μL was dropped on the test strip, and after developing for 15 minutes, a visual judgment was made.
[比較例1]
上記酵素処理および発酵を行わず、粉砕した大豆胚軸について、上記と同様にしてアレルゲンの検出を行った。
[Comparative Example 1]
Allergens were detected in the crushed soybean hypocotyls in the same manner as above without the above enzyme treatment and fermentation.
<6.結果>
アレルゲンが存在する場合には、図1に示すテストストリップにおいて、矢印で示す位置にバンドが出現するところ、酵素処理および発酵を経てエクオール含有組成物が回収された実施例1においてはアレルゲンの存在を示すバンドは検出されなかった。一方、酵素処理および発酵を経なかった比較例1においてはアレルゲンの存在を示すバンドが検出された。
以上より、本発明上記酵素処理および発酵を行うことで、実質的にアレルゲンを含まないエクオール含有組成物が得られることがわかった。
<6. Result>
When an allergen is present, the presence of the allergen is present in Example 1 in which the band appears at the position indicated by the arrow in the test strip shown in FIG. 1 and the equol-containing composition is recovered through enzymatic treatment and fermentation. The indicated band was not detected. On the other hand, in Comparative Example 1 which did not undergo enzyme treatment and fermentation, a band indicating the presence of an allergen was detected.
From the above, it was found that an equol-containing composition substantially free of allergens can be obtained by performing the above-mentioned enzyme treatment and fermentation of the present invention.
本発明の方法により製造されたエクオール含有組成物を、飲食品又は医薬品等として摂取することにより、乳癌、前立腺癌、骨粗しょう症、高コレステロール血症、心疾患、更年期障害等を予防できる。 By ingesting the equol-containing composition produced by the method of the present invention as a food or drink or a pharmaceutical product, breast cancer, prostate cancer, osteoporosis, hypercholesterolemia, heart disease, menopausal disorders and the like can be prevented.
Claims (11)
(2)前記工程(1)で産生された前記エクオールを含有するエクオール含有組成物を、前記培地から回収する工程、
を含む、実質的にアレルゲンを含まないエクオール含有組成物の製造方法。 (1) A plant of a legume family containing isoflavones is treated with an enzyme that converts the isoflavones into aglycone to obtain an enzyme-treated solution, and the enzyme-treated solution containing aglycone is fermented by an anaerobic microorganism. , The process of converting the aglycone to equol, and
(2) A step of recovering the equol-containing composition containing the equol produced in the step (1) from the medium.
A method for producing an equol-containing composition containing substantially no allergen.
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