Structural Insight into the Enzymatic Formation of Bacterial Stilbene

Takahiro Mori, Takayoshi Awakawa, Koichiro Shimomura, Yuri Saito, Dengfeng Yang, Hiroyuki Morita*, Ikuro Abe

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

22 被引用数 (Scopus)

抄録

In contrast to stilbene biosynthesis by type III polyketide synthase in plants, in bacteria stilbene is produced by the collaboration of two enzymes in Photorhabdus luminescens: the unusual β-ketosynthase StlD catalyzes the condensation of the β-ketoacyl starter with an α,β-unsaturated-acyl substrate (two C-C bond-forming reactions) to produce isopropylstyrylcyclohexanedione, which is subsequently converted to stilbene by the aromatase StlC. Here we report the in vitro characterizations of StlD and StlC, and the X-ray crystal structures of StlD. Interestingly, structure-based mutagenesis demonstrated that His302, within the conserved Cys-His-Asn triad, is not essential for the enzyme reaction, while Glu154 functions as a base-catalyst to activate the β-ketoacyl intermediate bound to the catalytic Cys126. The structures also revealed the presence of a putative nucleophilic water molecule activated by hydrogen bond networks with Glu154 and Ser340, suggesting that StlD employs novel catalytic machinery for the condensation of two acyl substrates to produce the cyclohexanedione scaffold.

本文言語英語
ページ(範囲)1468-1479
ページ数12
ジャーナルCell Chemical Biology
23
12
DOI
出版ステータス出版済み - 2016/12/22

ASJC Scopus 主題領域

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬理学
  • 創薬
  • 臨床生化学

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