Heterologous Expression of Fluostatin Gene Cluster Leads to a Bioactive Heterodimer,Organic Letters

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Heterologous Expression of Fluostatin Gene Cluster Leads to a Bioactive Heterodimer
Organic Letters ( IF 4.9 ) Pub Date : 2015-10-14 00:00:00 , DOI: 10.1021/acs.orglett.5b02683
Chunfang Yang _{1,

2} , Chunshuai Huang _{1,

2} , Wenjun Zhang ₁ , Yiguang Zhu ₁ , Changsheng Zhang ₁

Affiliation

The biosynthesis gene cluster (fls) for atypical angucycline fluostatins was identified from the marine derived Micromonospora rosaria SCSIO N160 and was confirmed by gene knockouts and the biochemical characterization of a bifunctional oxygenase FlsO2. The absolute configuration of the key biosynthetic intermediate prejadomycin was determined for the first time by Cu Kα X-ray analysis. Heterologous expression of the intact fls-gene cluster in Streptomyces coelicolor YF11 in the presence of 3% sea salts led to the isolation of two new compounds: fluostatin L (1) and difluostatin A (2). Difluostatin A (2), an unusual heterodimer, exhibited antibacterial activities.

中文翻译：

Fluostatin基因簇的异源表达导致生物活性异二聚体。

从海洋衍生的玫瑰红单孢菌SCSIO N160中鉴定出非典型的安古环素fluostatins的生物合成基因簇（fls），并通过基因敲除和双功能加氧酶FlsO2的生化特性得到了证实。通过CuKαX射线分析首次确定了关键生物合成中间体普鲁霉素的绝对构型。在3％的海盐存在下，链霉菌YF11中完整的fls基因簇的异源表达导致了两种新化合物的分离：氟他汀L（1）和双氟他汀A（2）。地氟他汀A（2）是一种不寻常的异二聚体，具有抗菌活性。

更新日期：2015-10-14

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