硫黄を含むサイクロペンタクロモンの生物合成のための酵素環収縮
Qiuyue Nie1,2,3, Chunxiao Sun1,2,3, Shuai Liu1,2,3
1Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania19104, United States.
Journal of the American Chemical Society
|December 16, 2024
まとめ
研究者達は 新しい酵素 IscL を発見し 自然な製品に含まれる 独特のサイクロペンタクロモン構造を作り出しました この酵素は
科学分野:
- 生物化学
- 自然製品の生物合成
- 酵素学
背景:
- サイクロペンタクロモンは,多くの生物活性天然製品の重要な構造モチーフです.
- サイクロペンタクロモンの生物合成経路と酵素的起源は,ほとんど不明のままである.
- 炭素と硫黄の結合を特徴とする新種のサイクロペンタクロモン誘導体であるイソクロモスルフィンが特定された.
研究 の 目的:
- サイクロペンタクロモン構造の形成に起因する酵素機構を解明する.
- サイクロペンタクロモン生物合成におけるキーリング収縮のステップを触媒する酵素を特定する.
- 特定された酵素の触媒的汎用性を調査し,キサントン前駆体を改変する.
主な方法:
- FAD依存のモノオキシゲナーゼの識別と特徴付け,IscLと指定されています.
- 2S-レミスポリンAの形成を研究するために,クサントンの前駆者を用いた酵素測定法.
- 触媒的結果 (リング収縮対分裂) を決定する重要な残留物の役割を調べるために,IscLのサイト指向型変異.
主要な成果:
- IscLは,ベンゼン環の収縮によって6/6/5サイクロペンタディエンの中間体である2S-レミスポリンAの形成を触媒化する.
- 2S-レミスポリンAは,イソクロモスルフィンを形成するために自発的にチオール-マイケルの添加を受けます.
- IscLの同類は,230の位置で重要な残留物によって調節された,ザントンの中間物質のリング収縮またはリング割れにつながるバイフォークされた活性を示します.
結論:
- FAD依存のモノオキシゲナーゼ IscLは,6/6/5サイクロペンタクロモンの核構造を確立する上で重要な役割を果たします.
- この研究は,リングの収縮を媒介する能力と基板特異性を含む,IscLの触媒機構を明らかにした.
- 発見は,サイクロペンタクロモンを含む天然製品のゲノムマイニングの基礎を提供し,バイオカタリシスのIscLの可能性を強調しています.
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