Nisin is a 34 amino acids anti-microbial peptide (lantibiotic). It first binds to lipid II and then forms, together with this cell wall synthesis precursor, small pores in the cytoplasmic membrane that lead to leakage of small molecules, including ATP, and subsequently to cell death. Because of its broad host spectrum, it is widely used as a preservative in food. Initially, nisin is ribosomally synthesized as a precursor. Subsequent enzymatic modifications introduce the unusual chemical and structural features of the molecule. Finally, the modified molecule is translocated across the cytoplasmic membrane and processed into its mature form. Biosynthesis of nisin is encoded by a cluster of 11 genes, of which the first gene, nisA, encodes the precursor of nisin. The other genes direct the synthesis of proteins that are involved in the modification, translocation and processing of nisin (nisB, nisC, nisP, and nisT), in the immunity against nisin (nisI, nisF, nisE, and nisG) and in the regulation of the expression of nisin genes (nisR and nisK). NisR and NisK belong to the family of bacterial two-component signal transduction systems. NisK is a histidine-protein kinase that resides in the cytoplasmic membrane and is proposed to act as a receptor for the mature nisin molecule. Upon binding of nisin to NisK, it autophosphorylates and transfers the phosphate group to NisR, which is a response regulator that becomes activated upon phosphorylation by NisK. Activated NisR* induces transcription of two out of three promoters in the nisin gene cluster: PnisA and PnisF. The promoter driving the expression of nisR and nisK is not affected. Because nisin induces its own expression the accumulation of small amounts of nisin in a growing culture leads to an auto-induction process.