Nosiheptide, an archetypal member of thiopeptide antibiotics, arises from post-translational modifications of a ribosomally synthesized precursor peptide that contains an N-terminal leader peptide (LP) sequence and a C-terminal core peptide (CP) sequence. Despite extensive efforts concerning the biosynthesis of thiopeptide antibiotics, the regulatory mechanisms in this process remain poorly understood. Using the nosiheptide-producingStreptomyces actuosusstrain as a model system, we report here that NosP, aStreptomycesantibiotic regulatory protein, serves as the only cluster-situated regulator and activates the transcription of all structural genes, which are organized into two divergently transcribed operons in thenoscluster, by binding to their intergenic region. NocP, the counterpart of NosP inNocardiasp., regulates the production of structurally related nocathiacin I in a similar manner. NosP activity senses the nosiheptide biosynthetic process by interactions with both peptidyl and small-molecule ligands that result from the LP and CP parts of the precursor peptide, respectively.

中文翻译：

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NosP调节的Nosepteptide生产对前体肽衍生的肽基和小分子配体都有反应。

诺西肽是硫肽抗生素的原型成员，源于包含N末端前导肽（LP）序列和C末端核心肽（CP）序列的核糖体合成前体肽的翻译后修饰。尽管在硫肽抗生素的生物合成方面进行了广泛的努力，但是在这一过程中的调节机制仍然知之甚少。使用产生诺西肽的链霉菌菌株作为模型系统，我们在此报告NosP，一种链霉菌抗生素调节蛋白，充当唯一的簇状调节剂，并激活所有结构基因的转录，这些基因在鼻孔簇中被组织成两个不同转录的操纵子。结合到它们的基因间区域。NocP，Nocardiasp中NosP的对应物，以类似的方式调节结构相关的Nocathiacin I的产生。NosP活性通过与分别由前体肽的LP和CP部分产生的肽基配体和小分子配体的相互作用来感知Nosiheptide的生物合成过程。