Krawczyk Joanna M, Völler Ginka H, Krawczyk Bartlomiej, Kretz Julian, Brönstrup Mark, Süssmuth Roderich D
Institut für Chemie, Technische Universität Berlin, 10623 Berlin, Germany.
Chem Biol. 2013 Jan 24;20(1):111-22. doi: 10.1016/j.chembiol.2012.10.023.
Labyrinthopeptins are class III lantibiotics produced by the actinomycete Actinomadura namibiensis. The most characteristic structural feature is the posttranslationally installed triamino triacid labionin with a quaternary α-carbon. In addition to the unique structure, labyrinthopeptin A2 possess remarkable antiviral and antiallodynic biological activities. To harness the substrate tolerance of the biosynthetic machinery, we developed an efficient system for the generation of labyrinthopeptin analogs. Streptomyces lividans was used as a heterologous host since the natural producer Actinomadura namibiensis remained genetically intractable. Generation of a library of 39 mutants allowed identification of variable and invariable regions in the labyrinthopeptin structures. Additional data on the flexibility of the biosynthetic machinery were provided by in vitro experiments. This study is detailed investigation on the potential to generate analogs of class III lantibiotics by genetic engineering.
迷宫肽是由嗜盐放线菌产生的III类羊毛硫抗生素。最具特征性的结构特征是翻译后安装的具有季α-碳的三氨基三酸拉比宁。除了独特的结构外，迷宫肽A2还具有显著的抗病毒和抗痛觉过敏生物活性。为了利用生物合成机制的底物耐受性，我们开发了一种高效的系统来生成迷宫肽类似物。由于天然生产者嗜盐放线菌在遗传上仍然难以处理，因此使用变铅青链霉菌作为异源宿主。生成39个突变体的文库可以鉴定迷宫肽结构中的可变区和不变区。体外实验提供了关于生物合成机制灵活性的更多数据。这项研究是对通过基因工程生成III类羊毛硫抗生素类似物潜力的详细研究。
