Saturation mutagenesis of selected residues of the α‐peptide of the lantibiotic lacticin 3147 yields a derivative with enhanced antimicrobial activity

Summary The lantibiotic lacticin 3147 consists of two ribosomally synthesized and post‐translationally modified antimicrobial peptides, Ltn α and Ltn β, which act synergistically against a wide range of G ram‐positive microorganisms. We performed saturation mutagenesis of specific residues of Ltn α to determine their functional importance. The results establish that Ltn α is more tolerant to change than previously suggested by alanine scanning mutagenesis. One substitution, Ltn α H 23 S , was identified which improved the specific activity of lacticin 3147 against one pathogenic strain, S taphylococcus aureus   NCDO 1499. This represents the first occasion upon which the activity of a two peptide lantibiotic has been enhanced through bioengineering.