Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes
Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes
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DOI：
10.1038/nchembio.175
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发表时间：
2009-06-01
影响因子：
14.8
通讯作者：
Pernodet, Jean-Luc
中科院分区：
文献类型：
--
作者：
Gondry, Muriel;Sauguet, Ludovic;Pernodet, Jean-Luc
环二肽及其衍生物属于二酮哌嗪（DKP）家族，其由广泛的天然产物组成，表现出有用的生物学性质。在少数已知的DKP生物合成途径中，非核糖体肽合成酶（NRPS）参与构成DKP支架的环二肽的合成，除了在albonoursin（1）途径中。Albonoursin或cyclo（alpha，beta-dehydroPhe-alpha，beta-dehydroLeu）是由诺尔斯链霉菌（Streptomyces noursei）产生的抗菌DKP。在该途径中，环（Phe-Leu）（2）中间体的形成由AlbC催化，AlbC是一种与NRPS无关的小蛋白。我们证明了AlbC使用氨酰-tRNA作为底物来催化DKP肽键的形成。此外，与AlbC具有中等相似性的其他几种细菌蛋白也使用氨酰-tRNA来合成各种环二肽。因此，AlbC和这些相关蛋白属于一个新定义的酶家族，我们将其命名为环二肽脱氢酶（CDPS）。
Cyclodipeptides and their derivatives belong to the diketopiperazine (DKP) family, which is comprised of a broad array of natural products that exhibit useful biological properties. In the few known DKP biosynthetic pathways, nonribosomal peptide synthetases (NRPSs) are involved in the synthesis of cyclodipeptides that constitute the DKP scaffold, except in the albonoursin (1) pathway. Albonoursin, or cyclo(alpha,beta-dehydroPhe-alpha,beta-dehydroLeu), is an antibacterial DKP produced by Streptomyces noursei. In this pathway, the formation of the cyclo(Phe-Leu) (2) intermediate is catalyzed by AlbC, a small protein unrelated to NRPSs. We demonstrated that AlbC uses aminoacyl-tRNAs as substrates to catalyze the formation of the DKP peptide bonds. Moreover, several other bacterial proteins, presenting moderate similarity to AlbC, also use aminoacyl-tRNAs to synthesize various cyclodipeptides. Therefore, AlbC and these related proteins belong to a newly defined family of enzymes that we have named cyclodipeptide synthases (CDPSs).