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Nature:羊毛硫抗生素生物合成的机制

摘要 : 乳酸链球菌肽 (含硫醚桥的羊毛硫抗生素家族的一个成员)在食品工业已广泛使用了超过40年,没有产生实质性的抗药性。

 

乳酸链球菌肽 (含硫醚桥的羊毛硫抗生素家族的一个成员)在食品工业已广泛使用了超过40年,没有产生实质性的抗药性。鉴于针对很多临床使用的抗生素的抗药性的出现,这一特性让人们尤为感兴趣。

Wilfred van der Donk及同事发表了“羊毛硫抗生素脱水酶”NisB (在乳酸链球菌肽生物合成中所涉及的一种酶)的X-射线结构,并通过生物化学数据显示,NisB将glutamyl-tRNAGlu用于Ser/Thr残基的临界活化。这些发现为在其他类别的天然产物的生物合成中所涉及的很多类似羊毛硫抗生素的脱水酶的功能表征提供了一个基础。

原文链接:Structure and mechanism of the tRNA-dependent lantibiotic dehydratase NisB

Lantibiotics are a class of peptide antibiotics that contain one or more thioether bonds. The lantibiotic nisin is an antimicrobial peptide that is widely used as a food preservative to combat food-borne pathogens1. Nisin contains dehydroalanine and dehydrobutyrine residues that are formed by the dehydration of Ser/Thr by the lantibiotic dehydratase NisB (ref. 2). Recent biochemical studies revealed that NisB glutamylates Ser/Thr side chains as part of the dehydration process3. However, the molecular mechanism by which NisB uses glutamate to catalyse dehydration remains unresolved. Here we show that this process involves glutamyl-tRNAGlu to activate Ser/Thr residues. In addition, the 2.9-Å crystal structure of NisB in complex with its substrate peptide NisA reveals the presence of two separate domains that catalyse the Ser/Thr glutamylation and glutamate elimination steps. The co-crystal structure also provides insights into substrate recognition by lantibiotic dehydratases. Our findings demonstrate an unexpected role for aminoacyl-tRNA in the formation of dehydroamino acids in lantibiotics, and serve as a basis for the functional characterization of the many lantibiotic-like dehydratases involved in the biosynthesis of other classes of natural products.

对应Nature杂志: 2015年01月22日Nature杂志精选

来源: Nature 浏览次数:60

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