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Nanopore DNA Sequencing for Metagenomic Soil Analysis
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カダシド,多剤耐性細菌に対して活性である土壌メタゲノムからのカルシウム依存酸性リポペプチド
Changsheng Wu1, Zhuo Shang1, Christophe Lemetre1
1Laboratory of Genetically Encoded Small Molecules , The Rockefeller University , New York , New York 10065 , United States.
Journal of the American Chemical Society
|February 9, 2019
まとめ
研究者達は 新しいカルシウム依存の抗生物質である カダシドを発見し 耐性菌に対して有効でした これらの新種のリポペプチドは 細胞壁の生物合成を妨害し 抗生物質耐性に対抗する有望な道を示しています
科学分野:
- 微生物学
- 生物化学
- 薬物の発見
背景:
- 抗生物質耐性は 世界的に広がる健康上の脅威です
- カルシウム依存抗生物質は,耐性病原体に対する多様なメカニズムを持つリポペプチドのクラスです.
- 非リボソームペプチド合成酵素 (NRPS) は,それらの組み立ての鍵です.
研究 の 目的:
- 新しいカルシウム依存抗生物質の特定と特徴づけ
- 耐性病原体に対する活性抗生物質の発見のための新しい戦略を探求する.
- カダサイド生産の遺伝的基盤を調査する.
主な方法:
- NRPSアデニレーション (AD) ドメインシーケンスを使用して,遺伝子クラスタを特定しました.
- メタゲノムDNAをスクリーニングし,cde生物合成遺伝子クラスタを回収した.
- ヘテロログな表現は化合物を生成し,分析するために使用された.
主要な成果:
- cde遺伝子クラスターは土壌メタゲノムから識別され,クローン化されました.
- 2つの新しい酸性リポペプチド,カダサイドAとBが生成された.
- カダシドは独特の構造を持ち,細胞壁の生物合成を阻害することで,多剤耐性グラム陽性病原体を抑制する.
- カルシウムが豊富な土壌では,カダサイドのような遺伝子クラスターが一般的です.
結論:
- カダシドは,カルシウム依存抗生物質の新しいサブファミリーを表しています.
- これらの化合物は,多剤耐性細菌によって引き起こされる感染症の治療の可能性を示しています.
- この発見は,抗生物質発見のためのNRPS配列化の有用性を強調し,カダサイド生物合成とカルシウム炭酸濃度の間の環境関連性を示唆しています.
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