バイオシンセシス・ガイダンスとテーラーリング酵素触媒によるディリラン型メロテルペノイドの標的発見
Zhaolun Sun1, Mengyue Wu1, Boyuan Zhong1
1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Journal of the American Chemical Society
|October 25, 2024
まとめ
研究者は生物合成の洞察を用いて,前例のない骨組みを含む 23の新しい真菌メロテルペノイドを発見しました. この研究は,真菌の天然製品とその潜在的抗炎症および殺虫剤の知識を拡張します.
科学分野:
- 自然製品化学
- キノコの代謝
- 酵素学
背景:
- ディリラン型メロテルペノイド (DMs) は,複雑な6/ 6/5/5のリング系を持つ希少な真菌代謝産物である.
- DMの化学的多様性と生物合成に関する知識は限られており,知られている化合物は11つだけです.
研究 の 目的:
- DMの発見と多様化のためのワークフローを開発する.
- DM形成に関与する生物合成経路と酵素メカニズムを探求する.
- 潜在的な生物学的活動を持つ新しいDMを特定する.
主な方法:
- 菌類の二次代謝基因群のゲノム採掘
- 先進的な分析技術を用いた代謝物質の分析
- ヘテロログの発現と in vitro 試験を含む 酵素触媒の調整
- 酵素メカニズムを解明するための結晶学と変異性研究.
主要な成果:
- 23人の新兵を特定した 7人の新兵は前代未聞だった
- ステレオダイバージェントリングの収縮を触媒化するα-ケトグルタレット依存酸素酵素であるDhiDの特徴.
- 構造的多様性に貢献するシトクロームP450であるDhiHの特徴化.
- DMの改変におけるDhiDの触媒的汎用性の実証
- バイオアッセイでは,分離された化合物の抗炎症および殺虫剤の作用が示された.
結論:
- 開発されたワークフローは,DMの既知の化学的多様性を大幅に拡張します.
- DhiDとDhiHは,DMの生物合成において重要な役割を果たし,酵素の汎用性を示しています.
- 特定されたDMは,新しい抗炎症剤と殺虫剤を開発するための有望な源です.
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