Maturation and secretion of nisin A from Lactococcus lactis

乳酸乳球菌（Lactococcus lactis）的I类细菌素nisin A （NisA）编码在一个11个基因簇上，该基因簇不仅包含结构基因NisA，还包含编码负责成熟、分泌、自身诱导和自身免疫的蛋白质的基因。NisA在核糖体上被翻译为57个氨基酸的前体，在细胞质中经历由NisB催化的脱水反应和随后由NisC催化的环化步骤。这些反应包括五种区域和立体选择反应。在abc转运体NisT分泌后，先导序列被枯草杆菌样蛋白酶NisP蛋白水解消化。在这个应用中，我们建议通过生物化学、生物物理和结构方法来分析单个成分的复杂相互作用及其时空协调。这些结果使我们能够在分子水平上理解导致NisA成熟和分泌的机制。

The class I bacteriocin nisin A (NisA) from Lactococcus lactis, a lantibiotic, is encoded on a 11 gene cluster that contains not only the structural gene NisA, but also genes coding for proteins responsible for maturation, secretion, auto-induction and auto-immunity. NisA, which is ribosomally translated as a 57 amino acid precursor, undergoes dehydratation reactions catalyzed by NisB and a subsequent cyclization step catalyzed by NisC in the cytosol. These reactions involve five regioand stereo-selective reactions. After secretion by the ABC-transporter NisT, the leader sequence is proteolytically digested by the subtilisin-like protease NisP. In this application, we propose to analyze the complex interplay of the individual components and their spatial and temporal coordination via biochemical, biophysical and structural approaches. These results should enable us to understand the mechanisms that result in the maturation and secretion of NisA on a molecular level.