Fakultät II-Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 124, 10623 Berlin, Germany.
J Am Chem Soc. 2012 Jun 20;134(24):9922-5. doi: 10.1021/ja3040224. Epub 2012 Jun 11.
The biosynthesis of a considerable number of ribosomally synthesized peptide antibiotics involves the modification of Ser and Thr residues of a precursor peptide. This post-translational processing is performed by one or multiple modifying enzymes encoded in the biosynthetic gene cluster. We present a deuterium-label based enzyme assay, utilizing a series of peptide substrates with α-deuterated Ser, for the determination of the dehydration order during the biosynthesis of class III lantibiotic labyrinthopeptin A2. Remarkably, the data show that, in contrast to other modifying enzymes of class I and II lantibiotics, LabKC has a C- to N-terminal processing mode. This surprising finding, which we consider relevant for the biosyntheses of other class III lantibiotics, underlines significant differences of this class of modifying enzymes compared to other investigated systems.
相当数量的核糖体合成肽抗生素的生物合成涉及到前体肽中丝氨酸和苏氨酸残基的修饰。这种翻译后加工是由生物合成基因簇中编码的一个或多个修饰酶完成的。我们提出了一种基于氘标记的酶测定法，利用一系列带有α-氘代丝氨酸的肽底物，来确定 III 类羊毛硫抗生素迷宫霉素 A2 生物合成过程中的脱水顺序。值得注意的是，数据表明，与 I 类和 II 类羊毛硫抗生素的其他修饰酶不同，LabKC 具有 C 到 N 端的加工模式。这一令人惊讶的发现，我们认为与其他 III 类羊毛硫抗生素的生物合成有关，突显了这类修饰酶与其他研究系统的显著差异。
