Study of purification technology of mycotoxin contaminated food using human drug metabolizing enzyme
| Project/Area Number |
15K12354
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Eating habits
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| Research Institution | Kobe University |
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Principal Investigator |
Imaishi Hiromasa 神戸大学, バイオシグナル総合研究センター, 教授 (50223318)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | アフラトキシン / P450 / CYP3A4 / 解毒 / シトクロムP450 / 変異原性 / 大腸菌 |
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| Outline of Final Research Achievements |
Aflatoxin B1 (AFB1) is a kind of mycotoxin mainly produced by Aspergillus flavus (A. flavus), and is known to have extremely high mutagenicity and carcinogenicity. In this study, we tried to develop a method to detoxify AFB1 under normal temperature and pressure by using human drug metabolizing enzyme. Human CYP3A4 is the main enzyme that converts AFB1 into aflatoxin B1-8,9-epoxide (AFBO) with high carcinogenicity in vivo. On the other hand, since AFBO is a very unstable reaction intermediate, it is known that AFBO is spontaneously decomposed into AFB1-8,9-dihydrodiol in about 5 seconds in vitro and loses mutagenicity promptly. In this study, we succeeded in preventing food poisoning caused by AFB1 by transiently converting AFB1 into highly toxic AFBO in vitro using E. coli that expresses human CYP3A4.
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| Academic Significance and Societal Importance of the Research Achievements |
アフラトキシンB1(AFB1)は、主にAspergillus flavus (A.flavus) により産生されるマイコトキシンの一種で、極めて高い変異原性、発がん性を持つことが知られている。これまで、放射線照射や酸処理などを用いた汚染食品中のアフラトキシン分解法が試みられてきた。しかしながら、これらの方法では食品成分に対する損傷が大きい事から、いずれも有効なAFB1の減毒法とはなっていない。そこで本研究では、ヒトの薬物代謝酵素を利用することで、常温・常圧下でAFB1を解毒する手法を開発した。これら一連の結果は、将来のカビ毒による被害を著しく低減できる可能性を示している。
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Report
(5 results)
Research Products
(19 results)
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[Journal Article] Modification of N-terminal amino acids of fungal benzoate hydroxylase (CYP53A15) for the production of p-hydroxybenzoate and optimization of bioproduction conditions in Escherichia coli.2018
Author(s)
Tamaki, S., Yagi, M., Nishihata, Y., Yamaji, H., Shigeri, Y., Uno, T., and Imaishi, H.
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Journal Title
J. Microbiol. Biotech.
Volume: 28
Issue: 3
Pages: 439-447
DOI
Related Report
Peer Reviewed
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[Journal Article] Point mutation of cytochrome P450 2A6 (a polymorphic allele CYP2A6.25) confers new substrate specificity towards flavonoids2015
Author(s)
Uno, T., Ogura, C., Izumi, C., Nakamura, M., Yanase, T., Yamazaki, H., Ashida, H., Kanamaru, K., Yamagata, H., Imaishi, H.
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Journal Title
Biopharm. Drug Dispos
Volume: 36
Pages: 552-563
Related Report
Peer Reviewed
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