A Methyltransferase Initiates Terpene Cyclization in Teleocidin B Biosynthesis

被引：70

作者：

Awakawa, Takayoshi ^{[1
]}

Zhang, Lihan ^{[1
]}

Wakimoto, Toshiyuki ^{[1
]}

Hoshino, Shotaro ^{[1
]}

Mori, Takahiro ^{[1
]}

Ito, Takuya ^{[2
]}

Ishikawa, Jun ^{[3
]}

Tanner, Martin E. ^{[4
]}

Abe, Ikuro ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan

[2] Tokushima Bunri Univ, Fac Pharmaceut Sci, Yamashiro, Tokushima 7708514, Japan

[3] Natl Inst Infect Dis, Shinjuku Ku, Tokyo 1628640, Japan

[4] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2014年 / 136卷 / 28期

关键词：

TUMOR PROMOTERS; TOXIC SUBSTANCE; STREPTOMYCES; ELUCIDATION; IDENTIFICATION; ACTIVATION; MECHANISM; PATHWAY;

D O I：

10.1021/ja505224r

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Teleocidin B is an indole terpenoid isolated from Streptomyces. Due to its unique chemical structure and ability to activate protein kinase C, it has attracted interest in the areas of organic chemistry and cell biology. Here, we report the identification of genes encoding enzymes for teleocidin B biosynthesis, including non-ribosomal peptide synthetase (tleA), P-450 monooxygenase (tleB), prenyltransferase (tleC), and methyltransferase (tleD). The tleD gene, which is located outside of the tleABC cluster on the chromosome, was identified by transcriptional analysis and heterologous expression. Remarkably, TleD not only installs a methyl group on the geranyl moiety of the precursor but also facilitates the nucleophilic attack from the electron-rich indole to the resultant cation, to form the indole-fused six-membered ring. This is the first demonstration of a cation, generated from methylation, triggering successive terpenoid ring closure.

引用

页码：9910 / 9913

页数：4

共 25 条

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