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An overview of lantibiotic biosynthetic machinery promiscuity and its impact on antimicrobial discovery

ABSTRACT Introduction: The continued emergence of drug resistant bacteria within the nosocomial and community environment recalcitrant to conventional antimicrobial therapies has enforced the requirement for novel therapeutics. This has led to a renewed interest in peptide antimicrobials, including ribosomally synthesized peptides termed lantibiotics. Lantibiotics represent a novel class of agents that many studies have highlighted as effective against a range of pathogenic bacteria. Areas covered: In this review, the modular nature of lantibiotic synthesis is discussed and how this can be exploited not only to improve known lantibiotics but also for the creation of new to nature lantibiotics exhibiting improved pharmacological properties, antimicrobial activity and ability to bypass bacterial resistance mechanisms. Expert opinion: The use of combinatorial biosynthetic systems to combine different modules or ring structures of known lantibiotics have also been utilized to create new to nature lantibiotics. To fully exploit the available information and its application to lantibiotic engineering, additional structure activity relationship (SAR) analysis is required to fully understand the impact of certain post-translational modifications and the impact they have upon the activity, stability and pharmacological properties.