Biosynthesis of diazepinomicin/ECO-4601, a micromonospora secondary metabolite with a novel ring system

被引：50

作者：

McAlpine, James B. ^{[1
]}

Banskota, Arjun H. ^{[1
]}

Charan, Romila D. ^{[2
]}

Schlingmann, Gerhard ^{[2
]}

Zazopoulos, Emmanuel ^{[1
]}

Piraee, Mahmood ^{[1
]}

Janso, Jeffrey ^{[2
]}

Bernan, Valerie S. ^{[2
]}

Aouidate, Mustapha ^{[1
]}

Farnet, Chris M. ^{[1
]}

Feng, Xidong ^{[2
]}

Zhao, Zhizi ^{[1
]}

Carter, Guy T. ^{[2
]}

机构：

[1] Thall Pharmaceut Inc, Montreal, PQ H4S 2C8, Canada

[2] Wyeth Res, Chem & Screening Sci, Pearl River, NY 10965 USA

来源：

JOURNAL OF NATURAL PRODUCTS | 2008年 / 71卷 / 09期

关键词：

D O I：

10.1021/np800376n

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

The novel microbial metabolite diazepinomicin/ECO-4601 (1) has a unique tricyclic dibenzodiazepinone core, which was unprecedented among microbial metabolites. Labeled feeding experiments indicated that the carbocyclic ring and the ring nitrogen of tryptophan Could be incorporated via degradation to the 3-hydroxyanthranilic acid, forming ring A and the nonamide nitrogen of 1. Genomic analysis of the biosynthetic locus indicated that the farnesyl side chain was mevalonate derived, the 3-hydroxyanthranilic acid moiety could be formed directly from chorismate, and the third ring was constructed via 3-amino-5-hydroxybenzoic acid. Successful incorporation of 4,6-D-2-3-hydroxyanthranilic acid into ring A of I via feeding experiments supports the genetic analysis and the allocation of the locus to this biosynthesis. These studies highlight the enzymatic complexity needed to produce this structural type, which is rare in nature.

引用

页码：1585 / 1590

页数：6

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