Maturation and secretion of nisin A from Lactococcus lactis

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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.