Combinatorial biosynthesis for the generation of new-to-nature peptide antimicrobials

Natural peptide products are a valuable source of important therapeutic agents, including antibiotics, antivirals and crop protection agents. Aided by an increased understanding of structure–activity relationships of these complex molecules and the biosynthetic machineries that produce them, it has become possible to re-engineer complete machineries and biosynthetic pathways to create novel products with improved pharmacological properties or modified structures to combat antimicrobial resistance. In this review, we will address the progress that has been made using non-ribosomally produced peptides and ribosomally synthesized and post-translationally modified peptides as scaffolds for designed biosynthetic pathways or combinatorial synthesis for the creation of novel peptide antimicrobials.