Advances in the arsenal of tools available enabling the discovery of novel lantibiotics with therapeutic potential

作者：Sandiford Stephanie Kate^*

来源：Expert Opinion on Drug Discovery, 2014, 9(3): 283-297.

DOI：10.1517/17460441.2014.877882

• anti-microbial
• bioinformatics
• biosynthesis
• genome mining
• heterologous expression
• infectious disease
• novel drugs

Introduction: Lantibiotics are ribosomally synthesised peptides, which undergo extensive post-translational modification. Their mode of action and effectiveness against multi-drug-resistant pathogens, and relatively low toxicity, makes them attractive therapeutic options.
Areas covered: This article provides background information on the four classes of lanthipeptides that have been described to date. Due to the clinical potential of these agents, specifically those from Class land II, it is essential to identify organisms that harbour potentially interesting clusters encoding novel lantibiotics. Multiple emerging technologies have been applied to address this issue, including genome mining and specific bioinformatics programs designed to identify lantibiotic clusters present within the genome sequences. These clusters can then be effectively expressed using optimised heterologous expression systems, which are ideally amenable to large-scale production.
Expert opinion: The continuing expansion of publicly available genomes, particularly genomes from microorganisms isolated from under-explored environments, combined with powerful bioinformatics tools able to accurately identify clusters of interest are of paramount importance in the discovery of novel lantibiotics. Detailed analysis of clusters drastically reduces dereplication time, which was often problematic when using the traditional method of isolation, purification and then identification. Allowing a more focused direction of 'wet lab' work, targeting the most promising agents, greatly increases the chance of novel lantibiotic discovery and development. High-throughput screening strategies are also required to enable the efficient analysis of these potentially clinically relevant agents.

• 出版日期2014-3