Characterization of a gene cluster of Staphylococcus warneri ISK-1 encoding the biosynthesis of and immunity to the lantibiotic, nukacin ISK-1

We characterized a gene cluster in a plasmid designated pPI-1 of Staphylococcus warneri ISK-1 encoding the biosynthesis of and immunity to the lacticin-481 type lantibiotic, nukacin ISK-1. The DNA sequence suggested that the nukacin ISK-1 gene cluster consists of at least six genes, nukA (a structural gene), -M, -T, -F, -E, -G, and two open reading frames, ORF1 and ORF7. NukM and NukT were predicted to be involved in post-translational modification and secretion of nukacin ISK-1 respectively. NukF, -E, and -G were predicted to form a membrane complex which contributes to self-protection from nukacin ISK-1. Transcriptional analyses revealed that nukM through ORF7 comprises an operon, and that ORF1 is transcribed independently from downstream of nukA. The transcriptional levels of the nukA and nukM genes were enhanced by osmotic stress. The expression level of the nukA transcript was scarcely enhanced by nukacin ISK-1, suggesting that expression is not under the control of the autoregulatory circuit.