Semi-in vitro Reconstitution of Roseocin, a Two-Component Lantibiotic from an Actinomycete

Lantibiotics are lanthionine containing peptide natural products that belong to the class of ribosomally synthesized and post-translationally modified peptides (RiPPs). Recent expansion in the availability of microbial genomic data and in silico analysis tools have accelerated the discovery of these promising alternatives to antibiotics. Following the genome-mining approach, a biosynthetic gene cluster for a putative two-component lantibiotic roseocin was identified in the genome of an Actinomycete, Streptomyces roseosporus NRRL 11379. Post-translationally modified lanthipeptides of this cluster were obtained by heterologous expression of the genes in E. coli, and were in vitro reconstituted to their bioactive form. The two lanthipeptides displayed antimicrobial activity against Gram-positive bacteria only synergistically, a property reminiscent of two-component lantibiotics. Structural analysis of the -component identified a disulfide bridge flanking two of its four thioether bridges and the {beta}-component having six thioether bridges with its C-terminus extended than the previously known two-component lantibiotics.