JP2012528826A - ビタミンK強化thyA(−)突然変異細菌 - Google Patents
ビタミンK強化thyA(−)突然変異細菌 Download PDFInfo
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- JP2012528826A JP2012528826A JP2012513598A JP2012513598A JP2012528826A JP 2012528826 A JP2012528826 A JP 2012528826A JP 2012513598 A JP2012513598 A JP 2012513598A JP 2012513598 A JP2012513598 A JP 2012513598A JP 2012528826 A JP2012528826 A JP 2012528826A
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- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
【選択図】図1
Description
(a):組成物中に0.10 μg/(ml又はg)のビタミンK2をもたらす量で存在し;そして
(i):前記細菌がthyA(-)突然変異体であり;かつ
(ii)前記細菌が:ラクトコッカス(Lactococcus)、ロイコノストック(Leuconostoc)及びバチルス(Bacillus)属からなる群から選択される細菌であり;そして
哺乳類のビタミンK欠乏症の処置及び/又は予防に使用される、前記組成物に関する。
(a):組成物中に0.10 μg/(ml又はg)以上のビタミンK2をもたらす量で存在し;そして
(i):前記細菌がthyA(-)突然変異体であり;かつ
(ii)前記細菌が:ラクトコッカス(Lactococcus)、ロイコノストック(Leuconostoc)及びバチルス(Bacillus)属からなる群から選択される細菌である。
組成物
上記で述べたように、本明細書中の商業的な組成物として、例えば、ヨーグルト又はチーズ等の、発酵乳生産物(乳性食品等)が挙げられる。
(A):動物の乳に本明細書中に記載のthyA(-)細菌を108〜1012cfu/ml播種する工程;及び
(B):当該乳を、4〜72時間、10℃〜50℃の温度で発酵させる工程;
により取得される。
「細菌」という用語は、本明細書中に記載の第一の側面において、複数形で用いられる。1個の細菌のみを含む組成物が本明細書中で言及されることはあり得ないからである。しかしながら、本明細書中の実施例で使用されるように、前記組成物は、例えば、109cfu/mlの同一種の細菌株、例えばMBP71(DSM12891)等を含んでもよいことは明らかである。
上記のように、本明細書中に記載の組成物は、
当該組成物中に存在する細菌の量が:
(a):組成物中に0.10 μg/(ml又はg)以上のビタミンK2をもたらす。
上記のように、本発明の知見(即ちthyA(-)突然変異体がビタミンK2を高度に含有すること)が得られる前は、当業者は、哺乳類におけるビタミンK欠乏症の処置及び/又は予防のために、本明細書中に記載のthyA(-)突然変異体を使用することにより生産された、機能性食品を商業化することを想到することは出来なかった。
ラクトコッカス・ラクティス(Lactococcus lactis)thyA(-)突然変異MBP71(DSM12891)のthyA(+)「野生型」/母株を、ここではMBP68と称する。
thyA(-)突然変異株MBP71は、対応するthyA(+)野生型株MBP68と比較して、約3倍のビタミンK2を生産した。
これらの試験の一つにおいて、実施例1のMBP71は、OD 0.5(実施例1ではOD 1.0であった)で乳に播種された。この場合、ビタミンK2の収量は、17μg/100mLであった。20mg/Lのチミジンが乳に添加された点を除いて同一条件の培養も準備された。この培養条件ではビタミンK2の収量は15μg/100mLであり、即ち、チミジン無しの培養条件とおおよそ同様であった。
この実施例は、直接的なdTTPの飢餓ではなく、むしろthyA遺伝子の不活性化により生じる代謝の変化により、ビタミンK2の増大が引き起こされることを示している。
上記結果がビタミンK2レベルの増大を引き起こす核酸代謝の一般摂動ではなかったことを示すために、発明者らは、ホスホリボシルアミン-グリシンリガーゼをコードするpurD(purDEKオペロンの一部)の欠失突然変異を、MBP71からMBP68を樹立したのと類似の方法により樹立した(データ無し)。
まとめると、実施例1〜3の結果から、thyAの突然変異が、ビタミンK2生産に対し、特異な影響を有することが示される。
1. Morishita T et al. 1999. Production of Menaquinones by Lactic Acid Bacteria. J. Dairy. Sci. 82: 1897-1903.
2. WO2008/040793A1 (Danone).
3. WO2008/040784A1 (Danone)
4. WO00/01799A2 (Chr. Hansen A/S)
5. Bolotin et. al 2001, Genome Res. 11 :731-753
6. JP 2001 136959 A
7. JP 2000 080043 A
8. Tsukamoto et al; "Construction of a Bacillus subtilis (natto) with High Productivity of Vitamin K2 (Menaquinone-7) by Analog Resistance"; Bioscience Biotechnology Bio-chemistry; vol. 65(9), pages 2007-2015, 2001
Claims (14)
- ビタミンK2を含有する細菌を含む組成物であり、当該組成物中に存在する細菌が:
(a):組成物中に0.10 μg/(ml又はg)のビタミンK2をもたらす量で存在し;そして
(i):前記細菌がthyA(-)突然変異体であり;かつ
(ii)前記細菌が:ラクトコッカス(Lactococcus)、ロイコノストック(Leuconostoc)及びバチルス(Bacillus)属からなる群から選択される細菌である;
哺乳類のビタミンK欠乏症の処置及び/又は予防に使用される、前記組成物。 - 前記組成物が食品である、請求項1に記載の組成物。
- 前記食品が、請求項1に記載のthyA(-)細菌で発酵させられた動物の乳である、即ち前記食品が乳製品(dairy product)である、請求項2に記載の組成物。
- 前記乳製品が:乳、ヨーグルト、及びチーズからなる群から選択される1つ以上の乳製品である、請求項3に記載の組成物。
- 前記発酵させられた動物の乳が:
(A):動物の乳に請求項1に記載のthyA(-)細菌を108〜1012cfu/ml播種する工程;及び
(B):当該乳を、4〜72時間、10℃〜50℃の温度で発酵させる工程;
により取得される、請求項3又は4のいずれかに記載の組成物。 - 請求項1に記載の乾燥単離thyA(-)突然変異細菌を含む組成物であり、医薬品である、請求項1に記載の組成物。
- 前記細菌がラクトコッカス・ラクティス(Lactococcus lactis)である、請求項1〜6のいずれか1項に記載の組成物。
- 前記ラクトコッカス・ラクティス(Lactococcus lactis)細菌が、ラクトコッカス・ラクティス亜種ラクティス(Lactococcus lactis subsp. lactis)又はラクトコッカス・ラクティス亜種クレモリス(Lactococcus lactis subsp. cremoris)である、請求項7に記載の組成物。
- 前記細菌が、受入番号DSM12891で供託された、thyA(-)ラクトコッカス・ラクティス亜種ラクティス(Lactococcus lactis subsp. lactis)突然変異株MBP71である、請求項8に記載の組成物。
- 請求項1に記載の組成物が、請求項1に記載のthyA(-)細菌を108〜1012cfu/(ml又はg)含む、請求項1〜9のいずれか1項に記載の組成物。
- 前記哺乳類がヒトである、請求項1〜10のいずれか1項に記載の組成物。
- 前記ビタミンK欠乏症の処置及び/又は予防が、ヒトの骨の健康の改善のために行われる、請求項11に記載の組成物。
- 前記骨の健康の改善が、骨の発達又は骨の強度の異常の減少に関する、請求項12に記載の組成物。
- 請求項1の(a)が、「組成物中に0.10 μg/mg以上のビタミンK2をもたらす量で存在し」である、請求項1〜13のいずれか1項に記載の組成物。
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EP09161782 | 2009-06-03 | ||
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PCT/EP2010/057629 WO2010139690A1 (en) | 2009-06-03 | 2010-06-01 | Bacteria thya(-) mutants with increased vitamin k |
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US8765118B2 (en) | 2010-08-17 | 2014-07-01 | Chr. Hansen A/S | Lactococcus lactis strain with high vitamin K2 production |
AU2011290850B2 (en) | 2010-08-17 | 2015-08-27 | Chr. Hansen A/S | Lactococcus lactis strain with high vitamin K2 production |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000001799A2 (en) * | 1998-07-03 | 2000-01-13 | Chr. Hansen A/S | Method of preventing bacteriophage infection of bacterial cultures |
JP2000080043A (ja) * | 1998-09-01 | 2000-03-21 | Hiroyuki Sumi | 水溶性ビタミンk剤 |
JP2000083653A (ja) * | 1998-09-08 | 2000-03-28 | New Food Creation Gijutsu Kenkyu Kumiai | ビタミンk高生産性菌株及びそれを用いたビタミンkの生産方法 |
JP2001136959A (ja) * | 1999-11-17 | 2001-05-22 | Hiroyuki Sumi | 枯草菌菌体および/またはその産生物を含む培養物、これに由来する水溶性ビタミンk誘導体、これらを含む医薬、食品および飼料ならびにこれらの製造方法 |
JP2007181461A (ja) * | 2005-12-29 | 2007-07-19 | Gnosis Spa | ビタミンk2の製造方法 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
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US7780961B2 (en) * | 2001-05-03 | 2010-08-24 | Actogenix N.V. | Self-containing Lactococcus strain |
US20050281756A1 (en) * | 2004-06-14 | 2005-12-22 | Eamonn Connolly | Use of lactic acid bacteria for decreasing gum bleeding and reducing oral inflammation |
FR2906817B1 (fr) | 2006-10-04 | 2012-04-06 | Gervais Danone Sa | Procede de culture pour favoriser la production de vitamine k2 par les bacteries lactiques et ses applications a la preparation de produits alimentaires |
FR2906816B1 (fr) * | 2006-10-04 | 2012-04-06 | Gervais Danone Sa | Variants de bacteries lactiques utiles pour produire la vitamine k2 et leurs applications a la preparation de produits alimentaires |
-
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- 2010-06-01 JP JP2012513598A patent/JP2012528826A/ja active Pending
- 2010-06-01 EP EP10724066.5A patent/EP2437758B1/en not_active Not-in-force
- 2010-06-01 CN CN201080024737.7A patent/CN102802647B/zh not_active Expired - Fee Related
- 2010-06-01 US US13/375,449 patent/US20120082651A1/en not_active Abandoned
- 2010-06-01 WO PCT/EP2010/057629 patent/WO2010139690A1/en active Application Filing
- 2010-06-01 KR KR1020117029181A patent/KR20120016642A/ko not_active Application Discontinuation
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000001799A2 (en) * | 1998-07-03 | 2000-01-13 | Chr. Hansen A/S | Method of preventing bacteriophage infection of bacterial cultures |
JP2000080043A (ja) * | 1998-09-01 | 2000-03-21 | Hiroyuki Sumi | 水溶性ビタミンk剤 |
JP2000083653A (ja) * | 1998-09-08 | 2000-03-28 | New Food Creation Gijutsu Kenkyu Kumiai | ビタミンk高生産性菌株及びそれを用いたビタミンkの生産方法 |
JP2001136959A (ja) * | 1999-11-17 | 2001-05-22 | Hiroyuki Sumi | 枯草菌菌体および/またはその産生物を含む培養物、これに由来する水溶性ビタミンk誘導体、これらを含む医薬、食品および飼料ならびにこれらの製造方法 |
JP2007181461A (ja) * | 2005-12-29 | 2007-07-19 | Gnosis Spa | ビタミンk2の製造方法 |
Non-Patent Citations (3)
Title |
---|
JPN6014024062; Applied and Environmental Microbiology Vol.68, No.6, 2002, p.3010-3023 * |
JPN6014024063; Applied and Environmental Microbiology Vol.68, No.11, 2002, p.5249-5257 * |
JPN6014024064; Biosci. Biotechnol. Biochem. Vol.65, No.9, 2001 * |
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HK1173947A1 (en) | 2013-05-31 |
EP2437758B1 (en) | 2014-05-07 |
DK2437758T3 (da) | 2014-07-21 |
CN102802647A (zh) | 2012-11-28 |
KR20120016642A (ko) | 2012-02-24 |
US8871195B2 (en) | 2014-10-28 |
EP2437758A1 (en) | 2012-04-11 |
US20120082651A1 (en) | 2012-04-05 |
CN102802647B (zh) | 2014-08-27 |
WO2010139690A1 (en) | 2010-12-09 |
US20130243742A1 (en) | 2013-09-19 |
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