Diversification of echinomycin molecular structure byway of chemoenzymatic synthesis and heterologous expression of the engineered echinomycin biosynthetic pathway

Echinomycin, a bis-intercalator antitumor cyclic peptide, is biosynthesized by a unique nonribosomal peptide synthetase (NRPS). Successful heterologous expression of the whole gene cluster of echinomycin in Escherichia coli let us to investigate a further application of echinomycin NRPS. To construct a cyclic peptide library, our approach through both chemoenzymatic and rational genetic engineering has been successfully demonstrated. These achievements provided the further support that E coli-based system can serve as a flexible yet robust platform for producing complex natural products and their analogs.