Entomopathogenic bacteria use multiple mechanisms for bioactive peptide library design
Entomopathogenic bacteria use multiple mechanisms for bioactive peptide library design
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DOI：
10.1038/nchem.2671
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发表时间：
2017-04-01
期刊：
影响因子：
21.8
通讯作者：
Bode, Helge. B.
中科院分区：
文献类型：
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作者：
Cai, Xiaofeng;Nowak, Sarah;Bode, Helge. B.
天然产物化合物库的产生在自然界中已被观察到用于不同的生物体，如细菌、真菌和植物;然而，关于产生这种化学多样性库的机制知之甚少。在这里，我们报告的机制，导致化学多样性的rhabdopeptide/xoblitide肽（RXPs）的生物合成。它们仅存在于与线虫共生的Photorhabdus属和Xellohabdus属的昆虫病原细菌中，所述线虫将它们递送给昆虫猎物，所述昆虫猎物被线虫和细菌杀死并用于营养。生物活性RXPs的化学多样性来自于单峰非核糖体肽合成酶的反复和灵活使用的组合，包括底物混杂、酶串扰和酶化学计量，如体内和体外实验所示。总之，这突出了自然界的多样化，或进化，天然产物的几种方法，并揭示了生物活性RXP的生物合成。
The production of natural product compound libraries has been observed in nature for different organisms such as bacteria, fungi and plants; however, little is known about the mechanisms generating such chemically diverse libraries. Here we report mechanisms leading to the biosynthesis of the chemically diverse rhabdopeptide/xenortide peptides (RXPs). They are exclusively present in entomopathogenic bacteria of the genera Photorhabdus and Xenorhabdus that live in symbiosis with nematodes delivering them to insect prey, which is killed and utilized for nutrition by both nematodes and bacteria. Chemical diversity of the biologically active RXPs results from a combination of iterative and flexible use of monomodular nonribosomal peptide synthetases including substrate promiscuity, enzyme cross-talk and enzyme stoichiometry as shown by in vivo and in vitro experiments. Together, this highlights several of nature's methods for diversification, or evolution, of natural products and sheds light on the biosynthesis of the bioactive RXPs.