Streptococcus macedonicus ACA-DC 198, a food-grade isolate from naturally fermented Greek Kasseri cheese, produces a lantibiotic named macedocin that has been previously purified and characterized. In the present study, a 15 171 bp region in the S. macedonicus ACA-DC 198 chromosome, containing the biosynthetic gene cluster of macedocin, has been sequenced. This region consists of 10 ORFs, which correspond to the genes (mcd genes) involved in macedocin biosynthesis, regulation and immunity. The mcd genes are organized in two operons and their role is predicted on the basis of similarities to genes of known lantibiotics. Compared with its closest match, the streptococcin A-FF22 gene cluster, the macedocin one contains an additional structural gene and an insertion sequence between the regulatory and the biosynthetic operons.