病原菌であるアスペルギルス・フミガトゥス (Aspergillus fumigatus) の非リボソーム性ペプチド合成酵素由来鉄 (((III)) コンプレックス
Wen-Bing Yin1, Joshua A Baccile, Jin Woo Bok
1Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Wisconsin 53706, USA.
Journal of the American Chemical Society
|January 31, 2013
まとめ
研究者は,キノコの小分子であるヘクサデヒドロアステクロム (HAS) を,アスペルギルス・フミガトゥスの主要な毒性因子として特定しました. その遺伝子クラスタを活性化すると,マウスの真菌感染症の重症度および死亡率が大幅に増加しました.
科学分野:
- 微生物学 微生物学とは
- 菌類学 菌類学とは
- バイオケミストリー バイオケミストリー
背景:
- 小分子 (SMs) は病原性微生物における重要な毒性因子ですが,そのほとんどは特徴づけられていないままです.
- ゲノムデータは,微生物のSMsの広大な未知のレパートリーを示唆しています.
研究 の 目的:
- 微生物の毒性における神秘的な遺伝子クラスターの機能を特定する.
- アスペルギルス・フミガトゥス (Aspergillus fumigatus) によって生成される新しい小分子について説明する.
主な方法:
- 遺伝子発現のマイクロアレイ分析.
- 菌類の変異株の比較代謝 (過剰発現とノックアウト).
- 小分子と生物合成経路の特定.
主要な成果:
- トリプトファン由来の鉄 (III) 複合体であるヘクサデヒドロアステクロム (HAS) が,暗号の主要産物として特定され,非リボソームペプチド合成酵素 (NRPS) 遺伝子クラスタを有する.
- ハスクラスタの活性化により,マウスモデルでの真菌の毒性および死亡率が増加しました.
- HASのための提案された生物合成経路を解明し,fumitremorgin生物合成とのクロストークを発見しました.
結論:
- ヘクサデヒドロアステクローム (HAS) は,アスペルギルス・フミガトゥスの主要な毒性因子である.
- HASのNRPS遺伝子クラスターは,HASの産生と真菌の病原性にとって重要である.
- 微生物のSMとその経路を理解することは,新しい治療戦略の開発に不可欠です.
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