Thioholgamides: Thioamide-Containing Cytotoxic RiPP Natural Products,ACS Chemical Biology

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Thioholgamides: Thioamide-Containing Cytotoxic RiPP Natural Products
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2017-10-17 00:00:00 , DOI: 10.1021/acschembio.7b00676
Louise Kjaerulff , Asfandyar Sikandar , Nestor Zaburannyi ₁ , Sebastian Adam , Jennifer Herrmann ₁ , Jesko Koehnke , Rolf Müller ₁

Affiliation

Thioviridamide is a structurally unique ribosomally synthesized and post-translationally modified peptide that contains several thioamide bonds and is active against a number of cancer cell lines. In the search for naturally occurring thioviridamide analogs, we employed genome mining that led to the identification of several related gene clusters. Chemical screening followed by cultivation and isolation yielded thioholgamides A and B, two new additions to the thioviridamide family with several amino acid substitutions, a different N-capping moiety, and with one less thioamide bond. Thioholgamides display improved cytotoxicity in the submicromolar range against a range of cell lines and an IC₅₀ of 30 nM for thioholgamide A against HCT-116 cells. Herein, we report the isolation and structural elucidation of thioholgamides A and B, a proposed biosynthetic cluster for their production, and their bioactivities against a larger panel of microorganisms and cancer cell lines.

中文翻译：

硫代汞齐：含硫酰胺的细胞毒性RiPP天然产物

硫代病毒酰胺是一种结构独特的核糖体合成和翻译后修饰的肽，含有几个硫酰胺键，对多种癌细胞具有活性。在寻找天然存在的硫代病毒酰胺类似物时，我们采用了基因组挖掘技术，从而鉴定了几个相关的基因簇。经过化学筛选，然后进行培养和分离，得到硫代氨基甲酸酯A和B，这是硫代病毒酰胺家族的两个新成员，具有多个氨基酸取代基，一个不同的N封端部分和一个较少的硫代酰胺键。硫代氨基甲酸酯类在亚微摩尔范围内对一系列细胞系和IC ₅₀表现出改善的细胞毒性30 nM的硫代氨基甲酸酯A对抗HCT-116细胞。在这里，我们报告了硫代氨基甲酸酯A和B的分离和结构解析，硫代氨基甲酸酯A和B是一种拟议的生物合成簇，用于其生产，以及它们对更大范围的微生物和癌细胞系的生物活性。

更新日期：2017-10-17

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