Combinatorial biosynthesis of nonribosomal lipopeptides

Nonribosomal peptides are a diverse group of structurally complex natural products that exhibit potent biological activities. In particular the nonribosomal lipopeptide antibiotics, including daptomycin, have emerged as key leads in the development of new antimicrobial agents that are effective against drug resistant pathogens. Recent studies have elucidated many of the key steps in precursor biosynthesis, assembly and tailoring of the lipopeptides. This knowledge has enabled new methods to be developed which have led to the engineered combinatorial biosynthesis of a wide range of 'non-natural' lipopeptide variants.