非リボソームペプチド合成酵素遺伝子群にインスパイアされた抗生物質

Xavier Vila-Farres^1,2, John Chu^1,2, Daigo Inoyama^1,2

¹Laboratory of Genetically Encoded Small Molecules and ‡Proteomics Resource Center, The Rockefeller University , New York, New York 10065, United States.

Journal of the American Chemical Society

|January 6, 2017

まとめ

研究者は新しい治療法を見つけるために細菌培養を回避しました生物情報学的予測と化学合成により,強力な抗生物質と抗真菌剤を含む合成生物情報学的天然製品 (syn-BNPs) が得られました.

科学分野:

微生物学
合成化学
バイオ情報学

背景:

バクテリア培養のスープ抽出物は,治療開発のための伝統的な源です.
培養方法は,細菌の生物合成多様性の全スペクトルへのアクセスを制限します.
培養の制限のため,潜在的微生物治療の重要な部分は未発見のままです.

研究の目的:

バクテリア培養を回避した新薬発見方法を開発する
細菌の遺伝子クラスターから新しい小分子を生物情報学的に予測し化学的に合成する
この新種の化合物から新しい抗菌剤と抗真菌剤を特定する.

主な方法:

生物合成遺伝子クラスター配列からの小分子構造の生物情報学的な予測.
合成生物情報学的天然製品 (syn-BNPs) を生み出すために予測された構造の化学合成.
微生物病原体に対する非リボソームペプチド合成酵素によるシン-BNPのスクリーニング.

主要な成果:

新しい抗生物質の発見耐性メカニズムを特定できない
菌類の病原体に対して有効な抗真菌剤の特定
新しい治療法の発見のための syn-BNPアプローチの有効性の実証.

結論:

生物情報学的予測と合成戦略は,細菌の生物合成多様性へのアクセスを大幅に拡大します.
このアプローチは新種の抗生物質と抗真菌薬の発見に有力な基盤を提供します
特定されたsyn-BNPsは,新しい抗感染療法のための有望なリードを表しています.

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