Functional analysis of modular enzymes and its application to the synthesis of antitumor agents
| Project/Area Number |
20310126
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Living organism molecular science
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| Research Institution | Hokkaido University |
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Principal Investigator |
OIKAWA Hideaki Hokkaido University, 大学院・理学研究院, 教授 (00185175)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2008: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
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| Keywords | 生理活性 / 酵素反応 / 微生物 / 生合成 / 有機化学 |
|---|
| Research Abstract |
Non-ribosomal peptide synthetase (NRPS) promotes condensations of amino acids forming amide linkages, with some modifications. We found that a single NRPS SfmC of the potent antitumor agents saframycin catalyzes a seven-step transformation from readily synthesized dipeptidyl substrates with long acyl chains into a pentacyclic tetrahydroisoquinoline scaffold. Based on deletion mutant analyses, we proposed the detailed mechanism involving the reductions of various peptidyl thioesters by an identical R-domain followed by the C-domain-mediated Pictet-Spengler reactions in an iterative manner.
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Report
(4 results)
Research Products
(51 results)
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[Journal Article] Solanapyrone Synthase, a Possible Diels-Alderase, and Iterative Type I Polyketide Synthase Encoded in a Biosynthetic Gene Cluster from Alternaria Solani.2010
Author(s)
K.Kasahara, T.Miyamoto, T.Fujimoto, H.Oguri, T.Tokiwano, H.Oikawa, Y.Ebizuka, I.Fujii
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Journal Title
ChemBioChem Vol.11, No.9
Pages: 1245-1252
Related Report
Peer Reviewed
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[Journal Article] Solanapyrone Synthase, a Possible Diels-Alderase, and Iterative Type 1 Polyketide Synthase Encoded in a Biosynthetic Gene Cluster from Alternaria Solani.2010
Author(s)
K.Kasahara, T.Miyamoto, T.Fujimoto, H.Oguri, T.Tokiwano, H.Oikawa, Y.Ebizuka, I.Fujii
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Journal Title
ChemBioChem
Volume: vol.11, No.9
Pages: 1245-1252
Related Report
Peer Reviewed
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[Journal Article] Biosynthetic gene-based secondary metabolite screening : a new diterpene, methyl phomopsenonate, from the fungus Phomopsis am ygdali2009
Author(s)
Toyomasu T., Kaneko A, Tokiwano T., Kanno Y., Kanno Y., Nuda R., Miura S., Nishioka T., Ikeda C., Mitsuhashi, W., Dairi T., Kawano T., Oikawa H., Kato N., Sassa T.
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Journal Title
J.Org.Chem. Vol.74, No.1
Pages: 1541-1548
Related Report
Peer Reviewed
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