メロクロリンA-D,サイクルメロテルペノイド抗生物質は,バナジウム依存のクロロペロキシダゼと異なる経路で生合成されます
Leonard Kaysser1, Peter Bernhardt, Sang-Jip Nam
1Scripps Institution of Oceanography, University of California, San Diego, California 92093, USA.
Journal of the American Chemical Society
|July 13, 2012
まとめ
海洋細菌は,新しい構造を持つ4つの新しいメロテルペノイド抗生物質,メロクロリンA-Dを産生しました. ヴァナジウム依存ハロペロキシダース遺伝子 (mcl40) は,それらのユニークな生物合成の鍵として特定されました.
科学分野:
- 自然製品化学とは
- マリン・マイクロバイオロジー
- バイオケミストリー バイオケミストリー
背景:
- メロテルペノイドは,多様な生物学的活動を持つ自然産物です.
- 海洋の微生物は,新しい生物活性化合物の源である.
- ストレプトマイケスの種は,抗生物質の生産者として知られています.
研究 の 目的:
- 海洋バクテリアから新しいメロテルペノイド抗生物質を発見し,特徴づけること.
- これらの新しい化合物の生物合成経路を解明するために.
- 主要な生合成のステップに責任を負う酵素を特定する.
主な方法:
- 新しいメロテルペノイドの分離と構造の解明.
- 産生バクテリアのゲノム配列の設計図.
- 生物合成遺伝子群の突然変異と異種発現.
- 酵素の機能を決定するための生化学的測定法.
主要な成果:
- 4つの新しいメロテルペノイド,メロクロリンA-D,前例のない化学的骨格が特定されました.
- メロクロリン生物合成に責任を負う57.6kbの遺伝子クラスタが特定されました.
- クラスター内で2つのヴァナジウム依存ハロペロキシダース (VHPO) 遺伝子が見つかりました.
- ヘテロログな発現は,Mcl40が新しいクロロニウム誘発マクロサイクライゼーションを触媒化することを明らかにした.
結論:
- メロクロリンA-Dは,メロテルペノイド抗生物質の新種である.
- メロクロリン生物合成遺伝子クラスターは,天然製品生物合成の洞察を提供します.
- VHPO Mcl40は,ユニークなマクロサイクリング反応を触媒化し,天然製品合成における既知の酵素変換のレパートリーを拡張します.
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