Biermann Friederike, Tan Bin, Breitenbach Milena, Kakumu Yuya, Nanudorn Pakjira, Dimitrova Yoana, Walker Allison S, Ueoka Reiko, Helfrich Eric J N
Institute for Molecular Bio Science, Goethe University Frankfurt Max-von-Laue Strasse 9 60438 Frankfurt am Main Germany
LOEWE Center for Translational Biodiversity Genomics (TBG) Senckenberganlage 25 60325 Frankfurt am Main Germany.
Chem Sci. 2024 Sep 10;15(42):17506-23. doi: 10.1039/d4sc03469d.
Ribosomally synthesized and posttranslationally modified peptides (RiPPs) constitute a diverse class of natural products. Atropopeptides are a recent addition to the class. Here we developed AtropoFinder, a genome mining algorithm to chart the biosynthetic landscape of the atropopeptides. AtropoFinder identified more than 650 atropopeptide biosynthetic gene clusters (BGCs). We pinpointed crucial motifs and residues in leader and core peptide sequences, prompting a refined definition of the atropopeptide RiPP family. Our study revealed that a substantial subset of atropopeptide BGCs harbors multiple tailoring genes, thus suggesting a broader structural diversity than previously anticipated. To verify AtropoFinder, we heterologously expressed four atropopeptide BGCs, which resulted in the identification of novel atropopeptides with varying peptide lengths, number and types of modifications. Atropopeptides serve as a proof-of-principle for the versatile genome mining approach developed in this study that can be repurposed for the identification of RiPP and other BGCs that currently evade detection.
核糖体合成及翻译后修饰肽（RiPPs）构成了一类多样的天然产物。阻转异构肽是该类别中的新成员。在此，我们开发了AtropoFinder，一种用于描绘阻转异构肽生物合成图谱的基因组挖掘算法。AtropoFinder识别出650多个阻转异构肽生物合成基因簇（BGCs）。我们确定了前导肽和核心肽序列中的关键基序和残基，促使对阻转异构肽RiPP家族进行了更精确的定义。我们的研究表明，相当一部分阻转异构肽BGCs含有多个修饰基因，因此表明其结构多样性比之前预期的更广泛。为了验证AtropoFinder，我们异源表达了四个阻转异构肽BGCs，从而鉴定出了具有不同肽长度、修饰数量和类型的新型阻转异构肽。阻转异构肽为本文开发的通用基因组挖掘方法提供了原理证明，该方法可用于识别目前难以检测到的RiPP和其他BGCs。
