| Project/Area Number |
25750382
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomolecular chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 生合成 / インドールテルペノイド / テルペン環化 / PKC activator / protein kinase C / 結晶構造解析 / 異種発現 / 放線菌 / teleocidin B / プレニル基転移酵素 / lyngbyatoxin A / メチル化酵素 |
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| Outline of Final Research Achievements |
Teleocidin B is a unique indole alkaloid, with an indolactam and a monoterpenoid moiety from Streptomyces blastmyceticus. This compound is also known as a potent protein kinase C activator, which is valuable pharmaceutically. We analyzed a prenyltransferase (TleC) and a methyltransferase (TleD) involved in teleocidin B biosynthesis. We analyzed the crystal structure of TleC, and identified its substrate-binding site. This is the first report of the structural analysis of prenyltransferase which forms C-C bond between C-3 of prenyl moiety and indole ring. With in vitro studies, we showed that TleD not only installed a methyl group on the geranyl moiety of the precursor, but also facilitated the nucleophilic attack to form the indole-fused six-membered ring. This is the first demonstration of a cation, generated from methylation, triggering successive terpenoid-ring closure. These results will pave the way for future studies to produce useful teleocidin B analogues by enzymes.
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