フォスフィノトリシンバイオシンセシスの過程で起こる異常な炭素-炭素結合分裂反応
Robert M Cicchillo1, Houjin Zhang, Joshua A V Blodgett
1Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Nature
|June 12, 2009
まとめ
研究者らは,前例のない酵素反応を再構成し,2-ヒドロキシエチルフォスフォナート (HEP) でのリン-炭素結合を割ってヒドロキシメチルフォスフォナート (HMP) を形成しました. この発見は,単核非ヘム鉄酵素とその触媒能力に関する知識を拡大する.
科学分野:
- バイオケミストリー バイオケミストリー
- 酵素学 酵素学とは
- 有機化学 オーガニック・ケミストリー
背景:
- リンと炭素の結合は,医学や農業のための天然製品において極めて重要です.
- フォスフィノトリシンとアラニンを含んだフォスフィノトリシントリペプチドは,遺伝子組み換え作物で使用されるBastaやLibertyのような除草剤の重要な成分です.
- 以前の研究では,2-ヒドロキシエチルフォスフォナート (HEP) が,フォスフィノトリシン三ペプチド生物合成中にヒドロキシメチルフォスフォナート (HMP) に変換されると示されました.
研究 の 目的:
- HEPをHMPに変換する新しいC(sp(3)) -C(sp(3)) 結合割れ反応を復元し,特徴づけること in vitro.
- この変換を起こす酵素の構造とメカニズムを解明する.
- 2-His-1-carboxylate mononuclear非ヘム鉄酵素家族によって触媒される既知の反応を拡張する.
主な方法:
- 酵素反応のインビトロ再構成.
- 酵素構造を決定するX線結晶学.
- 酵素活性とコファクター要件を分析するための生化学的測定法.
主要な成果:
- HEPのHMPとフォーマットへのC(sp(3)) -C(sp(3)) 結合割れをインビトロで成功裏に復元しました.
- 単核非ヘム鉄 (II) 依存型ダイオキシゲナーゼのX線結晶構造を決定しました.
- 酵素によるHEPの酸化消費は,ほとんどの関連酵素とは異なり,追加のコファクターや外因的な電子を必要としないことが実証されました.
結論:
- この研究は,前例のないHEPのHMPへの酵素変換を明らかにし,単核非ヘム鉄酵素の既知の触媒レパートリーを拡大しました.
- この発見は,このユニークなダイオキシゲネーゼに関する構造的およびメカニズム的な洞察を提供します.
- この研究は,フォスフィノトリシンの生物合成と,より広範な有機リン酸化学の分野を理解するのに寄与します.
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