A Cryptic Polyene Biosynthetic Gene Cluster in Streptomyces calvus Is Expressed upon Complementation with a Functional bldA Gene
A Cryptic Polyene Biosynthetic Gene Cluster in Streptomyces calvus Is Expressed upon Complementation with a Functional bldA Gene
复制标题
DOI：
10.1016/j.chembiol.2013.09.006
复制
发表时间：
2013-10-24
影响因子：
--
通讯作者：
Zechel, David L.
中科院分区：
文献类型：
--
作者：
Kalan, Lindsay;Gessner, Arne;Zechel, David L.
小牛链霉菌是最有名的氟化天然产物杀核素的生产者。这株链霉菌也是不寻常的，因为它表现出一种“秃”表型，即缺乏气生菌丝体和孢子的形成。该生物体的基因组测序揭示了bldA基因中的点突变，该点突变被预测为编码错误折叠的Leu-tRNA（UUA）分子。S.具有正确bldA拷贝的小牛恢复了孢子形成，并另外促进了多烯酸酰胺4-Z-阿尼霉素和少量异构体4-E-阿尼霉素的产生。生物测定表明，这些化合物抑制其他放线菌的形态分化。通过破坏研究鉴定并验证了编码1型聚酮合酶的阿尼霉素基因簇。这项研究强调了bldA基因在调节隐蔽生物合成基因表达中的重要性。
Streptomyces calvus is best known as the producer of the fluorinated natural product nucleocidin. This strain of Streptomycetes is also unusual for displaying a "bald" phenotype that is deficient in the formation of aerial mycelium and spores. Genome sequencing of this organism revealed a point mutation in the bldA gene that is predicted to encode a misfolded Leu-tRNA(UUA) molecule. Complementation of S. calvus with a correct copy of bldA restored sporulation and additionally promoted production of a polyeneoic acid amide, 4-Z-annimycin, and a minor amount of the isomer, 4-E-annimycin. Bioassays reveal that these compounds inhibit morphological differentiation in other Actinobacteria. The annimycin gene cluster encoding a type 1 polyketide synthase was identified and verified through disruption studies. This study underscores the importance of the bldA gene in regulating the expression of cryptic biosynthetic genes.