The candicidin gene cluster from Streptomyces griseus IMRU 3570
The candicidin gene cluster from Streptomyces griseus IMRU 3570
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DOI：
10.1099/00221287-148-1-51
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发表时间：
2002-01-01
期刊：
影响因子：
2.8
通讯作者：
Gil, JA
中科院分区：
文献类型：
--
作者：
Campelo, AB;Gil, JA
从灰色链霉菌IMRU 3570中克隆了一个205 kb的DNA区域，包括杀念菌素生物合成基因簇，并进行了部分测序。测序DNA的分析导致鉴定编码部分模块化聚酮合酶（PKS）的基因、硫酯酶基因、大环内酯环修饰基因、真菌胺生物合成基因和与大环内酯环的连接基因、杀念菌素输出基因和调节蛋白。它代表了芳香族多烯大环内酯生物合成基因簇的第一个广泛的遗传特征。特别令人感兴趣的是CanP1加载结构域（第一个被描述为负责芳香起始单元的活化）和多肽CanP3（携带用于形成七个共轭双键中的五个的模块）的存在。破坏编码杀念菌素起始单位的pabAB基因会使杀念菌素的产生消失[当向培养物中提供外源性对氨基苯甲酸时，杀念菌素的产生得以恢复]，并导致另一种抗真菌化合物的产生增强，而这种化合物在野生型中几乎检测不到。
A 205 kb DNA region from Streptomyces griseus IMRU 3570, including the candicidin biosynthetic gene cluster, was cloned and partially sequenced. Analysis of the sequenced DNA led to identification of genes encoding part a modular polyketide synthase (PKS), genes for thioesterase, macrolactone ring modification, mycosamine biosynthesis and attachment to the macrolide ring, candicidin export and regulatory proteins. It represents the first extensive genetic characterization of an aromatic polyene macrolide biosynthetic gene cluster. Of particular interest is the presence of the CanP1 loading domain (the first described as responsible for the activation of an aromatic starter unit) and the polypeptide CanP3 (carrying modules for the formation of five out of seven conjugated double bonds). Disruption of the pabAB gene that encodes the starter unit of candicidin abolished its production [which was restored when exogenous p-aminobenzoic acid was supplied to the culture] and resulted in an enhanced production of another antifungal compound that is barely detected in the wild-type.