2016 Fiscal Year Final Research Report
Unprecedented enzyme-catalyzed generation of complexity in fumagillin-pseurotin biosynthesis
| Project/Area Number |
26670048
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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 |
Natural medicines
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| Research Institution | Nihon Pharmaceutical University (2016)
University of Shizuoka (2014-2015) |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 生合成 / 天然物化学 / 物質生産 / 抗生物質 / 生物活性 / 酵素化学 / 微生物 / 反応機構 |
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| Outline of Final Research Achievements |
We identified a novel mechanism of an enzymatic trans-to-cis isomerization of an olefin that plays a part in generating the observed chemical diversity among the pseurotin-type fungal secondary metabolites. In vitro characterizations of pseurotin biosynthetic enzymes revealed that the glutathione-S-transferase PsoE required a participation of the bifunctional epoxidase-C-methyltransferase PsoF to complete the trans-to-cis isomerization of a pathway intermediate, presynerazol. The PsoE-glutathione-presynerazol complex crystal structure indicated that stereospecific glutathione-presynerazol conjugate formation is the principal function of PsoE. Moreover, this study revealed PsoF to have an additional, unexpected oxidative isomerase activity, making it a trifunctional enzyme that is key to the complexity generation in pseurotin biosynthesis.
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| Free Research Field |
天然物化学
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