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 |
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ページ(範囲) | 1468-1479 |
ページ数 | 12 |
ジャーナル | Cell Chemical Biology |
巻 | 23 |
号 | 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