Involvement and Unusual Substrate Specificity of a Prolyl Oligopeptidase in Class III Lanthipeptide Maturation
Involvement and Unusual Substrate Specificity of a Prolyl Oligopeptidase in Class III Lanthipeptide Maturation
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DOI：
10.1021/ja402296m
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发表时间：
2013-05-22
影响因子：
15
通讯作者：
Suessmuth, Roderich D.
中科院分区：
文献类型：
--
作者：
Voeller, Ginka H.;Krawczyk, Bartlomiej;Suessmuth, Roderich D.
羊毛硫肽代表了一组重要的核糖体合成和后修饰肽（RIPPs）。通常，在其成熟的最后步骤中，肽的一部分，称为前导序列，被去除，提供活性化合物。这一贡献描述了第一次识别的蛋白酶参与的III类lanthipeptide的前导肽的去除。在细菌基因组中鉴定了四个推定的III类生物合成基因簇，每个基因簇含有编码脯氨酰寡肽酶（POP）的基因。进一步在体外调查的基因簇从Kribbella flavida，涉及重建的生物合成的新lanthipeptide flavipeptin，证明了一个POP型FlaP蛋白酶是负责领导人删除。有趣的是，对底物特异性的详细体外研究表明，FlaP对翻译后修饰的肽具有特异性，并且可以区分N末端环和C末端环。因此，首次表明，除分子大小和氨基酸序列外，其他因素也可能参与持久性有机污染物对底物的识别。
Lanthipeptides represent an important group of ribosomally synthesized and post-translationally modified peptides (RiPPs). Commonly, in the last steps of their maturation, a part of the peptide, termed the leader, is removed, providing the active compound. This contribution describes for the first time the identification of a protease involved in the removal of the leader peptide of a class III lanthipeptide. Four putative class III biosynthetic gene clusters were identified in bacterial genomes, each containing a gene encoding a prolyl oligopeptidase (POP). Further in vitro investigations of the gene cluster from Kribbella flavida, involving reconstitution of the biosynthesis of the new lanthipeptide flavipeptin, proved that a POP-type FlaP protease is responsible for leader removal. Interestingly, detailed in vitro studies of the substrate specificity revealed that FlaP is specific to the post-translationally modified peptide and can discriminate between N- and C-terminal rings. Therefore, it has been shown for the first time that factors other than size and amino acid sequence might be involved in substrate recognition by POPs.