Cacaoidin, First Member of the New Lanthidin RiPP Family
Cacaoidin, First Member of the New Lanthidin RiPP Family
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DOI：
10.1002/anie.202005187
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发表时间：
2020-07-27
影响因子：
16.6
通讯作者：
Genilloud, Olga
中科院分区：
文献类型：
--
作者：
Javier Ortiz-Lopez, Francisco;Carretero-Molina, Daniel;Genilloud, Olga
抗菌素是一类核糖体合成和翻译后修饰的多肽(RIPPS)，其特征是含有羊毛硫氨酸或甲基羊毛硫氨酸环及其抗菌活性。Cacaoidin是从可可链霉菌中分离得到的一种新型糖基化抗生素，其结构经核磁共振、质谱学、化学衍生化和基因组分析等手段确证。新分子结合了突出的结构特征，例如大量的d-氨基酸，罕见的糖基化酪氨酸残基和前所未有的N，N-二甲基兰硫氨酸。后者的特点是将可可素放在一个新的RIPP家族中，该家族位于羊毛肽和亚麻素之间，这里称为羊毛肽。Cacaoidin对包括艰难梭菌在内的革兰氏阳性病原菌显示出很强的抗菌活性。该生物合成基因簇与其他已知的羊毛肽或芳樟素的同源性较低，提示了一条新的RIPP生物合成途径。
Lantibiotics are ribosomally synthesized and post-translationally modified peptides (RiPPs) characterized by the presence of lanthionine or methyllanthionine rings and their antimicrobial activity. Cacaoidin, a novel glycosylated lantibiotic, was isolated from a Streptomyces cacaoi strain and fully characterized by NMR, mass spectrometry, chemical derivatization approaches and genome analysis. The new molecule combines outstanding structural features, such as a high number of d-amino acids, an uncommon glycosylated tyrosine residue and an unprecedented N,N-dimethyl lanthionine. This latter feature places cacaoidin within a new RiPP family located between lanthipeptides and linaridins, here termed lanthidins. Cacaoidin displayed potent antibacterial activity against Gram-positive pathogens including Clostridium difficile. The biosynthetic gene cluster showed low homology with those of other known lanthipeptides or linaridins, suggesting a new RiPP biosynthetic pathway.