Post-translational Modification in Microviridin Biosynthesis
Post-translational Modification in Microviridin Biosynthesis
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DOI：
10.1002/cbic.200800560
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发表时间：
2008-12-15
期刊：
影响因子：
3.2
通讯作者：
Hemscheidt, Thomas K.
中科院分区：
文献类型：
--
作者：
Philmus, Benjamin;Christiansen, Guntram;Hemscheidt, Thomas K.
蓝细菌是生物活性天然产物的多产者，这些生物活性天然产物大多属于非核糖体肽和聚酮类。在这里，我们展示了如何微绿素K，一个新的成员的microviridin类的肽酶抑制剂，线性前体肽被加工成为成熟的三环肽酶抑制剂。阿加迪毕赤酵母的微病毒素（mvd）生物合成基因簇由六个编码微病毒素K、一种明显不表达的第二种微病毒素、两种RimK同源物、一种乙酰转移酶和一种ABC转运蛋白的基因组成。我们过量表达了该途径的三种酶，并通过化学降解和质谱分析证实了它们在体外的生化功能。我们表明，前肽通过RimK同系物MvdD和MvdC分别通过酯键和酰胺键形成的交联进行翻译后修饰。二氧化硅中对MVD基因簇的分析表明，微病毒素样化合物有可能在广泛的细菌中广泛存在。
Cyanobacteria are prolific producers of bioactive natural products that mostly belong to the nonribosomal peptide and polyketide classes. We show here how a linear precursor peptide of microviridin K, a new member of the microviridin class of peptidase inhibitors, is processed to become the mature tricyclic peptidase inhibitor. The microviridin (mvd) biosynthetic gene cluster of P. agardhii comprises six genes encoding microviridin K, an apparently unexpressed second microviridin, two RimK homologues, an acetyltransferase, and an ABC transporter. We have over-expressed three enzymes of this pathway and hove demonstrated their biochemical function in vitro through chemical degradation and mass spectrometry. We show that a prepeptide undergoes post-translational modification through cross-linking by ester and amide bond formation by the RimK homologues MvdD and MvdC, respectively. in silica analysis of the mvd gene cluster suggests the potential for widespread occurrence of microviridin-like compounds in a broad range of bacteria.