Structures and Comparative Characterization of Biosynthetic Gene Clusters for Cyanosporasides, Enediyne-Derived Natural Products from Marine Actinomycetes
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- 作者：Amy L. Lane ; Sang-Jip Nam ; Takashi Fukuda ; Kazuya Yamanaka ; Christopher A. Kauffman ; Paul R. Jensen ; William Fenical ; Bradley S. Moore
- 刊名：The Journal of the American Chemical Society
- 出版年：2013
- 出版时间：March 20, 2013
- 年：2013
- 卷：135
- 期：11
- 页码：4171-4174
- 全文大小：281K
- 年卷期：v.135,no.11(March 20, 2013)
- ISSN：1520-5126
文摘
Cyanosporasides are marine bacterial natural products containing a chlorinated cyclopenta[a]indene core of suspected enediyne polyketide biosynthetic origin. Herein, we report the isolation and characterization of novel cyanosporasides C鈥揊 (3鈥?b>6) from the marine actinomycetes Salinispora pacifica CNS-143 and Streptomyces sp. CNT-179, highlighted by the unprecedented C-2鈥?N-acetylcysteamine functionalized hexose group of 6. Cloning, sequencing, and mutagenesis of homologous 50 kb cyanosporaside biosynthetic gene clusters from both bacteria afforded the first genetic evidence supporting cyanosporaside鈥檚 enediyne, and thereby p-benzyne biradical, biosynthetic origin and revealed the molecular basis for nitrile and glycosyl functionalization. This study provides new opportunities for bioengineering of enediyne derivatives and expands the structural diversity afforded by enediyne gene clusters.