Advances in non-ribosomal peptides discovery, biosynthesis and modes of action against drug resistant bacteria

Abstract

The growing concern of antimicrobial-resistant (AMR) bacteria has created an urgent need for new antimicrobial agents with novel mechanisms of action. Non-ribosomal peptides (NRPs) have gained significant attention because they target essential and highly conserved bacterial structures through diverse mechanisms of action against many multidrug-resistant (MDR) pathogens. NRPs have distinct and diverse modes of action that reduce the likelihood of rapid AMR among bacteria. Advances in multi-omics approaches have greatly improved the discovery of novel NRPs In addition, synthetic biology, NRPS and domain engineering, and heterologous expression systems have expanded the possibilities for producing new peptide analogs with improved biological properties. This review discusses the major microbial sources of NRPs, their biosynthesis, recent approaches in NRP discovery and engineering, and their mechanisms of action against MDR pathogens along with challenges associated with NRP development, including silent biosynthetic gene clusters, low production yield, complex biosynthetic pathways, toxicity, and large-scale production with future prospects for developing NRP-based therapeutics to combat antimicrobial resistance.

Keywords

Multi-drug resistance / Bacterial metabolites / Non-ribosomal peptides

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