Russell Alicia H, Vior Natalia M, Hems Edward S, Lacret Rodney, Truman Andrew W
Department of Molecular Microbiology, John Innes Centre Norwich NR4 7UH UK
Chem Sci. 2021 Aug 2;12(35):11769-11778. doi: 10.1039/d1sc01456k. eCollection 2021 Sep 15.
Ribosomally synthesised and post-translationally modified peptides (RiPPs) are a structurally diverse class of natural product with a wide range of bioactivities. Genome mining for RiPP biosynthetic gene clusters (BGCs) is often hampered by poor annotation of the short precursor peptides that are ultimately modified into the final molecule. Here, we utilise a previously described genome mining tool, RiPPER, to identify novel RiPP precursor peptides near YcaO-domain proteins, enzymes that catalyse various RiPP post-translational modifications including heterocyclisation and thioamidation. Using this dataset, we identified a novel and diverse family of RiPP BGCs spanning over 230 species of Actinobacteria and Firmicutes. A representative BGC from J1074 (formerly known as ) was characterised, leading to the discovery of streptamidine, a novel amidine-containing RiPP. This new BGC family highlights the breadth of unexplored natural products with structurally rare features, even in model organisms.
核糖体合成及翻译后修饰肽（RiPPs）是一类结构多样的天然产物，具有广泛的生物活性。对RiPP生物合成基因簇（BGCs）进行基因组挖掘时，常常因最终被修饰成最终分子的短前体肽注释不佳而受阻。在此，我们利用先前描述的基因组挖掘工具RiPPER，在YcaO结构域蛋白附近识别新型RiPP前体肽，YcaO结构域蛋白是催化包括杂环化和硫代酰胺化在内的各种RiPP翻译后修饰的酶。利用该数据集，我们鉴定出一个新型且多样的RiPP BGC家族，其跨越230多种放线菌和厚壁菌。对来自J1074（以前称为 ）的一个代表性BGC进行了表征，从而发现了链脒，一种新型的含脒RiPP。这个新的BGC家族凸显了即使在模式生物中，具有结构罕见特征的未开发天然产物的广度。
