| Project/Area Number |
18K05418
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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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| Review Section |
Basic Section 38020:Applied microbiology-related
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| Research Institution | Sojo University |
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Principal Investigator |
OKA Takuji 崇城大学, 生物生命学部, 教授 (50510690)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 糖転移酵素 / 糸状菌 / ガラクトマンナン / ガラクトフラノース / 細胞壁 / 抗真菌薬 / アスペルギルス症 / 糖鎖 / Aspergillus fumigatus / cell wall / galactomannan / galactofuranose / glycosyltransferase / sugar chain / oligosaccharide / biosynthesis / アスペルギルス / 感染症 |
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| Outline of Final Research Achievements |
Many of the fungi that cause diseases to humans and crops are filamentous fungi belonging to the subphylum Pezizomycotina. The cell walls of filamentous fungi belonging to the subphylum Pezizomycotina contain a polysaccharide structure called galactomannan (GM), which is essential for the normal growth of the hyphae, and its biosynthetic enzymes are expected to be new targets for antifungal drugs. In this study, we found that GfsA, GfsB, and GfsC are responsible for the biosynthesis of β-(1→5)-galactofuranosyl chains in the GM structure of the pathogenic filamentous fungus Aspergillus fumigatus, and that CmsA and CmsB are responsible for the biosynthesis of core-mannan by biochemical and reverse genetic approaches. In particular, significant growth inhibition was observed in cmsA and cmsB disrupted-strains, suggesting that CmsA and CmsB may be new targets for antifungal drugs. We also clarified the protein structure of CmsA.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、深在性真菌症は増加している。侵襲性肺アスペルギルス症の治療薬であるアゾール系抗真菌薬に対する耐性株が世界的な脅威となっていることから、これまでと異なる作用機序を有する抗真菌薬の開発が急がれている。本研究では、構造の発見から長らく知られていなかった糸状菌のガラクトマンナン生合成を担う糖転移酵素群の詳細を明らかにした。特に、cmsAおよびcmsBの遺伝子破壊株では著しい生育阻害が認められたことから、CmsAおよびCmsBが抗真菌薬の標的となることが期待される。また、CmsAのタンパク質立体構造が明らかにされたことから、構造情報を基盤とした本酵素の阻害薬の開発が期待できる。
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