Prepeptide sequence of cinnamycin (Ro 09–0198): the first structural gene of a duramycin‐type lantibiotic

The tetracyclic polypeptide antibiotic cinnamycin (Ro 90–0198) belongs to the duramycin‐type lantibiotics and contains the unusual amino acids threo‐3‐methyl‐lanthionine, meso‐lanthionine, lysinoalanine and 3‐hydroxy‐aspartic acid. Its structural gene, referred to as cinA, has been identified on isolated chromosomal DNA of the Ro 09–0198‐producing strain Streptoverticillium griseoverticillatum via a 39‐residue oligonucleotide probe derived from fragment 7–19 of the hypothetical prolantibiotic sequence CRQSCSFGPFTFVCDGNTK. This propeptide part was then found within an open reading frame of 77 amino acids. In contrast to the nisin‐type prelantibiotics, this first duramycin‐type prelantibiotic has an unusually long leader sequence of 58 amino acids. It also differs in the processing site and the direction of the formation of the threo‐3‐methyl‐lanthionine bridges is from N‐terminal cysteine to C‐terminal dehydrated threonine residues, whereas the meso‐lanthionine and lysinoalanine bridges are formed by addition reactions from C‐terminal cysteine or lysine to N‐terminal dehyrated serine residues.