ファルネシル二酸化合成:基質選択性とステレオ選択性との妥協の芸術
Hirekodathakallu V Thulasiram1, C Dale Poulter
1Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Journal of the American Chemical Society
|December 7, 2006
まとめ
ファルネシル二リン酸合成酵素は,鎖の延長中に意外にいくつかのZ二重結合同位体を生成し,ステレオ選択性と基板結合のバランスを示しています. これは複数の種にまたがり,in vivoで起こります.
科学分野:
- 酵素学 酵素学とは
- バイオケミストリー バイオケミストリー
- 有機化学 オーガニック・ケミストリー
背景:
- ファルネシル二酸化酸 (FPP) 合成酵素は,イソプレノイドの合成に不可欠であり,イソペンテニル二酸化酸 (IPP) 単位のヘッド・トゥ・テール凝縮を触媒化する.
- この酵素ファミリーは,C5イソプレン単位の追加中に通常E二重結合を導入し, (E,E) -FPPに導きます.
- これらの反応のステレオ化学的結果は,下流の代謝経路にとって非常に重要です.
研究 の 目的:
- 鎖の延長中のFPP合成酵素のステレオ化学的忠誠度を調査する.
- ゲラニル二酸化物 (GPP) とFPPの合成中にZ二重結合イソマーが形成されるかどうかを決定する.
- IPP凝縮中の二重結合形成と水素損失のメカニズムを解明する.
主な方法:
- 様々な源 (鳥類,E. coli,A. tridentata,P. furiosus,M. thermautotrophicus) から精製されたFPP合成酵素を基板でインキュベーションする.
- 反応産物 (C10およびC15) の分析,染色学を用いてE-およびZ-同位体を特定する.
- デウテリウムの組み込みを追跡するために,同位体でラベル付けされた基板,特に (R) - [2-2H]IPPと (S) - [2-2H]IPPの使用.
主要な成果:
- 小量のZ二重結合イソマーであるネリル二酸化物 (Z-C10) と (Z,E) -FPPは,予想されるEイソマーと共に検出されました.
- これらのZ-同位体は,複数の生物で,in vivo条件下で形成された.
- (S) - [2-2H]IPPからのデュテリウムは製品に組み込まれ, (R) - [2-2H]IPPからのデュテリウムは含まれず,IPPのC2におけるプロ-R水素の損失を示しています.
結論:
- FPP合成酵素は,この酵素ファミリーでは予期せぬ,Z二重結合イソマーを生成することができる.
- Z-同位体の形成は,二重結合のステレオ選択性を最適化することと,IPPの結合部位からDMAPPを除外することの間の潜在的な妥協を示唆する.
- IPPからのプロ-R水素のステレオスペシフィック損失は,E-およびZ-同位体合成の両方で保存されます.
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