Insights into the Generation of Structural Diversity in a tRNA-Dependent Pathway for Highly Modified Bioactive Cyclic Dipeptides
Insights into the Generation of Structural Diversity in a tRNA-Dependent Pathway for Highly Modified Bioactive Cyclic Dipeptides
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DOI：
10.1016/j.chembiol.2013.04.017
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发表时间：
2013-06-20
影响因子：
--
通讯作者：
Marahiel, Mohamed A.
中科院分区：
文献类型：
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作者：
Giessen, Tobias W.;von Tesmar, Alexander M.;Marahiel, Mohamed A.
nocazines是一个新定义的抗菌和细胞毒性环二肽家族，由不同的放线菌种产生。本文中，我们在达松诺卡菌中鉴定了一个灭卡因生物合成基因簇，并描述了通向灭卡因家族成员nocazine E和XR334的生物合成途径。二酮哌嗪（DKP）的形成是由trna依赖的环二肽合成酶（CDPS）进行的，显示出未知的产物特征，而DKP支架的剪裁是通过环二肽氧化酶和两种不同的sam依赖的O-/ n -甲基转移酶的组合作用来实现的。我们的研究结果有助于阐明nocazine家族结构多样性的生物合成逻辑，并为探索修饰环二肽作为宿主-病原体和宿主-寄生虫相互作用的可能介质的生物学功能奠定了基础。
The nocazines are a newly defined family of antibacterial and cytotoxic cyclic dipeptides produced by different actinobacterial species. Here, we identify a nocazine biosynthetic gene cluster in Nocardiopsis dassonvillei and describe the elucidation of the biosynthetic pathway leading to the nocazine family members nocazine E and XR334. Diketopiperazine (DKP) formation is carried out by a tRNA-dependent cyclodipeptide synthase (CDPS) showing an unknown product profile, while tailoring of the DKP-scaffold is achieved through the combined and combinatorial action of a cyclodipeptide oxidase and two distinct SAM-dependent O-/N-methyltransferases. Our results help to illuminate the biosynthetic logic resulting in the structural diversity of the nocazine family and set the stage for exploring the biological function of modified cyclic dipeptides as possible mediators of host-pathogen and host-parasite interactions.