Thioviridamide is a structurally novel ribosomally synthesized and post-translational modified peptide (RiPP) produced by Streptomyces olivoviridis NA005001. It is characterized by a structure that features a series of thioamide groups and possesses potent antiproliferative activity in cancer cell lines. Its unusual structure allied to its promise as an anticancer compound led us to investigate the diversity of thioviridamide-like pathways across sequenced bacterial genomes. We have isolated and characterized three diverse members of this family of natural products. This characterization is supported by transformation-associated recombination cloning and heterologous expression of one of these compounds, thiostreptamide S4. Our work provides an insight into the diversity of this rare class of compound and indicates that the unusual N-terminus of thioviridamide is not introduced biosynthetically but is instead introduced during acetone extraction. A detailed analysis of the biological activity of one of the newly discovered compounds, thioalbamide, indicates that it is highly cytotoxic to cancer cells, while exhibiting significantly less activity toward a noncancerous epithelial cell line.

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基于基因组学的方法鉴定具有选择性抗癌活性的硫代维达酰胺样化合物

硫代病毒酰胺是寡链链霉菌产生的一种结构新颖的核糖体合成和翻译后修饰的肽（RiPP）。NA005001。它的特征是具有一系列硫酰胺基的结构，并在癌细胞系中具有强大的抗增殖活性。它与众不同的结构与其作为抗癌化合物的前景紧密相关，这使我们研究了测序细菌基因组中硫代病毒酰胺样途径的多样性。我们已经分离并鉴定了该天然产物家族的三个不同成员。这些化合物之一的硫链霉菌酰胺S4的转化相关重组克隆和异源表达支持了这种表征。我们的工作提供了对这种稀有化合物的多样性的见解，并指出了不寻常的N硫代病毒酰胺的末端不是生物合成引入的，而是在丙酮提取过程中引入的。对一种新发现的化合物硫代乙酰胺的生物活性的详细分析表明，它对癌细胞具有高度的细胞毒性，而对非癌性上皮细胞系的活性却大大降低。