Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2013 May 21;110(21):8483-8. doi: 10.1073/pnas.1307111110. Epub 2013 May 6.
Berninamycin is a member of the pyridine-containing thiopeptide class of antibiotics that undergoes massive posttranslational modifications from ribosomally generated preproteins. Berninamycin has a 2-oxazolyl-3-thiazolyl-pyridine core embedded in a 35-atom macrocycle rather than typical trithiazolylpyridine cores embedded in 26-atom and 29-atom peptide macrocycles. We describe the cloning of an 11-gene berninamycin cluster from Streptomyces bernensis UC 5144, its heterologous expression in Streptomyces lividans TK24 and Streptomyces venezuelae ATCC 10712, and detection of variant and incompletely processed scaffolds. Posttranslational maturation in S. lividans of both the wild-type berninamycin prepeptide (BerA) and also a T3A mutant generates macrocyclic compounds as well as linear variants, which have failed to form the pyridine and the macrocycle. Expression of the gene cluster in S. venezuelae generates a variant of the 35-atom skeleton of berninamycin, containing a methyloxazoline in the place of a methyloxazole within the macrocyclic framework.
伯林霉素是一种含吡啶硫肽类抗生素，其在核糖体生成的前体蛋白上经历了大量的翻译后修饰。伯林霉素具有一个 2-噁唑基-3-噻唑基-吡啶核心，嵌入在一个 35 原子大环中，而不是典型的三噻唑基吡啶核心嵌入在 26 原子和 29 原子肽大环中。我们描述了从链霉菌伯氏 UC5144 中克隆的 11 个基因伯林霉素簇，其在链霉菌光产色链霉菌 TK24 和委内瑞拉链霉菌 ATCC10712 中的异源表达，以及变体和不完全加工支架的检测。在链霉菌光产色链霉菌中，野生型伯林霉素前肽（BerA）和 T3A 突变体的翻译后成熟都生成了大环化合物和线性变体，这些变体未能形成吡啶和大环。在委内瑞拉链霉菌中表达基因簇会产生伯林霉素的 35 原子骨架变体，其中大环框架内的一个甲氧基恶唑啉取代了一个甲氧基恶唑。
