Functional analyses of teleocidin B biosynthetic enzymes
| 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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Report
(3 results)
Research Products
(11 results)
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[Journal Article] A methyltransferase initiates terpene cyclization in teleocidin B biosynthesis2014
Author(s)
Awakawa, T., Zhang, L., Wakimoto, T., Hoshino, S., Mori, T., Ito, T., Ishikawa, J., Tanner, M. E., Abe, I.
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Journal Title
J. Am. Chem. Soc.
Volume: 136
Issue: 28
Pages: 9910-9913
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] A methyltransferase initiates terpene cyclization in teleocidin B biosynthesis2015
Author(s)
Awakawa, T., Mori, T., Zhang, L., Wakimoto, T., Hoshino, S., Ito, T., Ishikawa, J., Tanner, M. E., Abe, I.
Organizer
Natural Product Discovery & Development in the Post Genomic Era by Society for industrial microbiology and biotechnology
Place of Presentation
San Diego, USA
Year and Date
2015-01-11 – 2015-01-14
Related Report
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[Presentation] Cyclohexene ring formation facilitated by methylation of the prenyl chain in teleocidin B4 biosynthesis2014
Author(s)
Awakawa, T., Mori, T., Zhang, L., Wakimoto, T., Hoshino, S., Ito, T., Ishikawa, J., Tanner, M. E., Abe, I.
Organizer
248th ACS National Meeting & Exposition
Place of Presentation
San Francisco, USA
Year and Date
2014-08-10 – 2014-08-14
Related Report
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