Streptocollin, a type IV lanthipeptide produced by Streptomyces collinus Tü 365

Lanthipeptides are ribosomally synthesized and posttranslationally modified microbial secondary metabolites. Here, we report the identification and isolation of streptocollin from Streptomyces collinus Tü 365, a new member of the class IV lanthipeptides. Insertion of the constitutive ermE* promoter upstream of the lanthipeptide synthetase gene stcL successfully triggered peptide production. Furthermore the streptocollin gene cluster was heterologously expressed in S. coelicolor M1146 and M1152, resulting in 3.5-fold and 5.5-fold increased yields, respectively.The structure and ring topology of streptocollin were determined by high resolution MS/MS analyses. Streptocollin contains four macrocyclic rings, including one lanthionine and three methyllanthionine residues. To the best of our knowledge, this is the first report on the isolation of a class IV lanthipeptide in preparative amounts, and on the successful heterologous expression of a class IV lanthipeptide gene cluster.