プラテンシミシンにおけるエーテル環の生物合成起源
Jeffrey D Rudolf1, Liao-Bin Dong1, Karina Manoogian1
1Department of Chemistry, ‡Department of Molecular Therapeutics, and §Natural Products Library Initiative at The Scripps Research Institute, The Scripps Research Institute , Jupiter, Florida 33458, United States.
Journal of the American Chemical Society
|December 15, 2016
まとめ
研究者は,プラテンシミシン (PTM) とプラテンシン (PTN) の異なる生物合成経路を制御する2つの重要な遺伝子,ptmT3とptmO5を特定しました. これらの発見は,PTMの重要な構造的要素を明らかにします.
科学分野:
- 自然製品の生物合成
- 微生物の二次代謝
- 酵素触媒
背景:
- プラテンシミシン (PTM) とプラテンシン (PTN) は,脂肪酸合成を阻害する細菌のディターペノイドである.
- PTMは選択的にFabF/FabBを抑制し,PTNはFabF/FabBとFabHを抑制する.
- 以前の研究では,PTMカセットがケトリド生物合成を分断する役割を特定しました.
研究 の 目的:
- ディターペノイドケトリド生物合成の分岐における PTM カセットの役割を調査する.
- PTMとPTNの生物合成の違いに 責任のある特定の遺伝子を特定する.
- PTM/PTN経路における PtmT3とPtmO5の機能を明らかにする.
主な方法:
- E. coliにおけるディターペンの生成システムの構築
- ストレプトマイセス・プラテンシスSB12029 (PTM-PTN二重生産者) の遺伝子操作
- 遺伝子不活性化 (ptmO5) と,蓄積したPTM/PTN共生体の分析.
主要な成果:
- ptmT3とptmO5をPTM/PTNの生物合成の分岐における重要な遺伝子として特定した.
- PtmT3は新しい細菌のI型ディテルペン合成体 ((16R) - エント - カウラン - 16 - オール合成体) である.
- PtmO5 (cytochrome P450) は,PTMエーテルリングを形成している可能性があり,その無活性化により,新しい共生物質が生じる.
結論:
- PTMカセット,特にPtmT3とPtmO5は,PTMとPTNケトリドの異なる生物合成を決定する.
- 11S,16S-エーテルリング,またはC-16立体化学は,PTMの抗菌作用に不可欠です.
- 新しい細菌のディターペン合成の発見と,PTM/PTNの生物合成と構造-活性関係に関する洞察.
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