Elucidation of novel archaeal mevalonate pathways oriented to metabolic engineering application
| Project/Area Number |
23580111
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied microbiology
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| Research Institution | Nagoya University |
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Principal Investigator |
HEMMI Hisashi 名古屋大学, 生命農学研究科, 准教授 (60302189)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 酵素 / 微生物 / 生体分子 / イソプレノイド / メバロン酸経路 / アーキア / 代謝 / フラビン酵素 |
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| Research Abstract |
A part of reactions in the archaeal mevalonate pathways were unidentified. Thus we performed the conversion assay of radio-labeled substrates by cell-free extract from archaea and functional characterization of archaeal homologs of known mevalonate pathway-related enzymes. As the result, we discovered the classical mevalonate pathway, which is rare in archaea, from an archaeon of genus Sulfolobus, and a novel modified pathway, which passes through 3-phosphomevalonate, from an archaeon of genus Thermoplasma.
We also performed X-ray crystal structural studies on type 2 isopentenyl diphosphate isomerase and diphosphomevalonate decarboxylase from archaea of genus Sulfolobus. The obtained structures and the results of various analyses showed novel mechanisms of catalysis, regulation of activity, and thermostabilization.
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Report
(4 results)
Research Products
(47 results)
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[Journal Article] (R)-mevalonate 3-phosphate is an intermediate of the mevalonate pathway in Thermoplasma acidophilum2014
Author(s)
Azami, Y., Hattori, A., Nishimura, H., Kawaide, H., Yoshimura, T. & Hemmi, H.
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Journal Title
Journal of Biological Chemistry
Volume: (in press)
Related Report
Peer Reviewed
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[Journal Article] Biochemical evidence supporting the presence of the classical mevalonate pathway in the thermoacidophilic archaeon Sulfolobus solfataricus2013
Author(s)
Nishimura, H., Azami, Y., Miyagawa, M., Hashimoto, C., Yoshimura, T. & Hemmi, H.
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Journal Title
Journal of Biochemistry
Volume: vol. 153
Pages: 415-420
Related Report
Peer Reviewed
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[Journal Article] Substrate-induced change in the quaternary structure of type 2 isopentenyl diphosphate isomerase from Sulfolobus shibatae2012
Author(s)
Nakatani, H., Goda, S., Unno, H., Nagai, T., Yoshimura, T. & Hemmi, H.
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Journal Title
Journal of Bacteriology
Volume: vol. 194
Pages: 3216-3224
Related Report
Peer Reviewed
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[Journal Article] Covalent modification of reduced flavin mononucleotide in type-2 isopentenyl diphosphate isomerase by active-site-directed inhibitors2011
Author(s)
Nagai, T., Unno, H., Janczak, M.W., Yoshimura, T., Poulter, C.D. & Hemmi, H.
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Journal Title
Proceedings of the National Academy of Sciences of the United States of America
Volume: vol. 108
Pages: 20461-20466
Related Report
Peer Reviewed
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[Journal Article] Structure and mutation analysis of archaeal geranylgeranyl reductase2011
Author(s)
Sasaki, D., Fujihashi, M., Iwata, Y., Murakami, M., Yoshimura, T., Hemmi, H. & Miki, K.
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Journal Title
Journal of Molecular Biology
Volume: 409
Pages: 543-557
Related Report
Peer Reviewed
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