| Project/Area Number |
18510190
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | University of Shizuoka |
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Principal Investigator |
ABE Ikuro University of Shizuoka, School of Pharmaceutical Sciences, Lecturer (40305496)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,940,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | Plant Polyketide Synthase / Chalcone Svnthase / Type III Polyketide Synthase / Structure Function Analvsis / Biosynthesis / Engineered Biosynthesis / Bioloeil Activity / Secondary Metabolism / 酵素機能改変 / 二次代謝酵素 / 生理活性物質 / 非天然型天然物 |
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| Research Abstract |
1. Pentaketide chromone synthase (PCS) from Aloe arborescens is a novel plant-specific type III polyketide synthase (PKS) that produces 5, 7-dihydroxy-2-methylchromone from five molecules of malonyl-CoA. On the basis of the crystal structures of wild-type and M207G mutant PCS, F80A/Y82A/M207G triple mutant was constructed and shown to produce an unnatural novel nonaketide naphthopyrone by sequential condensations of nine molecules of malonyl-CoAs. This is the first demonstration of the formation of a nonaketide by the structurally simple type III PKS. A homology model predicted that the active-site cavity volume of the triple mutant is increased to four times of that of the wild-type PCS.
2. A novel aldo-keto reductase (AKR) was cloned and sequenced from roots of A. arborescens. A. arborescens AKR share similarities with known plant AKRs, maintaining most of the active-site residues conserved in the AKR superfamily enzymes.
3. Benzalacetone synthase from Rheum palmatum efficiently catalyzed condensation of N-methylanthraniloyl-CoA (or anthraniloyl-CoA) with malonyl-CoA (or methylmalonyl-CoA) to produce 4-hydroxy-2 (1H) -quinolones, a novel alkaloidal scaffold produced by a type III polyketide synthase (PKS). Manipulation of the functionally divergent type III PKSs by non-physiological substrate thus provides an efficient method for production of pharmaceutically important quinolone alkaloids.
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