Thiostrepton Maturation Involving a Deesterification-Amidation Way To Process the C-Terminally Methylated Peptide Backbone
Thiostrepton Maturation Involving a Deesterification-Amidation Way To Process the C-Terminally Methylated Peptide Backbone
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硫链丝菌肽成熟涉及脱酯化-酰胺化方式来处理 C 末端甲基化肽主链
DOI：
10.1021/ja1111173
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发表时间：
2011-03-09
影响因子：
15
通讯作者：
Liu, Wen
中科院分区：
文献类型：
--
作者：
Liao, Rijing;Liu, Wen
硫肽是一类具有临床意义的高度修饰的肽类抗生素。它们的生物合成具有共同的特征核心形成模式，但在定制以提供个体成员方面有所不同。在这里，我们报告了一个不寻常的脱乙酰氨基-酰胺化过程中硫链丝菌素成熟，以提供终端酰胺部分。TsrB作为羧酸酯酶，催化甲酯中间体的水解以提供羧酸酯中间体，羧酸酯中间体可以通过酰胺转移酶Tsrc转化为酰胺产物。这些发现揭示了前体肽的C-末端甲基化，其在硫链丝菌素生物合成中是隐蔽的，但在其同源系列硫肽的形成中可能是常见的，所述硫肽在C-末端形式中变化为甲酯、羧酸酯或酰胺。
Thiopeptides are a class of clinically interesting and highly modified peptide antibiotics. Their biosyntheses share a common paradigm for characteristic core formation but differ in tailoring to afford individual members. Herein we report an unusual deesterification-amidation process in thiostrepton maturation to furnish the terminal amide moiety. TsrB, serving as a carboxylesterase, catalyzes the hydrolysis of the methyl ester intermediate to provide the carboxylate intermediate, which can be converted to the amide product by an amidotransferase, TsrC. These findings revealed a C-terminal methylation of the precursor peptide, which is cryptic in thiostrepton biosynthesis but potentially common in the formation of its homologous series of thiopeptides that vary in the C-terminal form as methyl ester, carboxylate, or amide.