2007 Fiscal Year Final Research Report Summary
Analysis of a physiological role and anti-asthmatic activity of the chitinase inhibior allosamidin
| Project/Area Number |
17380072
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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 |
Bioproduction chemistry/Bioorganic chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SAKUDA Shohei The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor (80192087)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Hiromasa Kyushu University, Hospital, Lecturer (30264039)
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| Project Period (FY) |
2005 – 2007
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| Keywords | enzyme inhibitor / chitin / chitinase / asthma / physiological activity / secondary metabolite / allosamidin / Streptomyces |
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| Research Abstract |
Allosamidin, a secondary metabolite of Streptomyces, inhibits family 18 chitinases which are widely present in nature Allosamidin has been used to study the physiological role of chitinases in a variety of organisms. Recently, two novel biological activities of allosamidin were found. One is the anti-asthmatic activity toward mammals. The other is the chitinase-production promoting activity toward its producing bacterium. In this project, we investigated the molecular mechanism of allosamidin in each of the biological activities.
Demethylallosamidin, an allosamidin derivative, was found to show much stronger anti-asthmatic activity than allosamidin. Photoaffinity and biotinylated probes of allosamidin and demethylallosamidin were prepared to detect allosamidins-binding proteins in the lung of asthma model mouse. Ym1, a chitinase-like protein, was identified as the main specific allosamidin-binding protein. Affinity of allosamidin and demethylallosamidin for Ym1 was very high (K_D value is around 10^<-8> M). Demthylallosamidin showed stronger binding affinity for Ym1 than allosamidin. Work to clarify the physiological function of Ym1 by using allosamidins is now in progress.
Allosamidin promoted chitinase production of an allosamidin-producing Streptomyces in a chitin medium at low concentrations such as 60 nM. The chitinase gene whose expression is enhanced by allosamidin was shown to have a direct repeat moiety in the promoter region and two genes encoding a two-component regulatory system at the 5''-upstream region. Gene disruption experiment showed that expression of the chitinase gene is induced by N, N''-diacetylchitobiose and allosamidin can enhance the expression through the two-component regulatory system. Allosamidin promotes chitinase production of Streptomyces species widely. It is important to investigate the physiological function of allosamidin in a chitin-rich environment such as in soils.
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[Presentation] Mechanism of chitinase-production promoting activity of allosamidin and its generality2007
Author(s)
Shigeo Suzuki, Naofumi Tagawa, Naoya Kikuchi, Tomoya Yoshinari, Katsushiro Miyamoto, Hiroshi Tsujibo, Takeshi Watanabe, Yasuo Ohnishi, SueharuHorinouchi, Hiromichi Nagasawa, Shohei Sakuda
Organizer
21st Chitin and Chitosan Symposium
Place of Presentation
Kobe
Year and Date
2007-07-27
Description
「研究成果報告書概要(欧文)」より
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