Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research and Pharmaceutical Biotechnology, Saarland University, Campus, Building E8.1, 66123, Saarbrücken, Germany.
Helmholtz Center for Infection Research (HZI), Department Microbial Drugs, Inhoffenstraße 7, 38124, Braunschweig, Germany.
Angew Chem Int Ed Engl. 2017 Jun 19;56(26):7407-7410. doi: 10.1002/anie.201612640. Epub 2017 May 23.
Secondary metabolome mining efforts in the myxobacterial multiproducer of natural products, Chondromyces crocatus Cm c5, resulted in the isolation and structure elucidation of crocagins, which are novel polycyclic peptides containing a tetrahydropyrrolo[2,3-b]indole core. The gene cluster was identified through an approach combining genome analysis, targeted gene inactivation in the producer, and in vitro experiments. Based on our findings, we developed a biosynthetic scheme for crocagin biosynthesis. These natural products are formed from the three C-terminal amino acids of a precursor peptide and thus belong to a novel class of ribosomally synthesized and post-translationally modified peptides (RiPPs). We demonstrate that crocagin A binds to the carbon storage regulator protein CsrA, thereby inhibiting the ability of CsrA to bind to its cognate RNA target.
次级代谢产物挖掘工作在黏细菌多产物天然产物的 Chondromyces crocatus Cm c5 中进行，导致了 crocagins 的分离和结构阐明，这是一种新型的多环肽，含有一个四氢吡咯并[2,3-b]吲哚核心。该基因簇是通过结合基因组分析、在生产者中靶向基因失活和体外实验的方法来鉴定的。基于我们的发现，我们开发了 crocagin 生物合成的生物合成方案。这些天然产物是由前体肽的三个 C 末端氨基酸形成的，因此属于一类新型的核糖体合成和翻译后修饰肽（RiPPs）。我们证明 crocagin A 与碳储存调节剂蛋白 CsrA 结合，从而抑制 CsrA 结合其同源 RNA 靶标的能力。
