Heterologous Expression, Biosynthesis, and Mutagenesis of Type II Lantibiotics from Bacillus licheniformis in Escherichia coli

Lichenicidin is a class II two-component lantibiotic produced by Bacillus licheniformis. It is composed of the two peptides Bli alpha and Bli beta, which act synergistically against various Gram-positive bacteria. The lichenicidin gene cluster was successfully expressed in Escherichia coli, thus constituting the first report to our knowledge of a full reconstitution of a lantibiotic biosynthetic pathway in vivo by a Gram-negative host. This system was further exploited to characterize and assign the function of proteins encoded in the biosynthetic gene cluster in the maturation of lichenicidin peptides. Moreover, a trans complementation system was developed for expression of Blia and Blip variants in vivo. This contribution will spur future studies in the heterologous expression and engineering of lantibiotics.