Echinomycin is a nonribosomal peptide (NRP) secondary metabolite from several streptomycetes that belongs to the large family of quinoxaline antibiotic/anticancer natural products. The members of this class of compounds have bicyclic aromatic quinoxaline chromophores attached to the C₂ symmetric cyclic peptide core structure.
　Isolation and sequencing of the entire echinomycin biosynthetic gene cluster from Streptomyces lasaliensis has been accomplished. Eight genes (ecm2-4, 8, 11-14) are predicted to be involved in the biosynthesis of quinoxaline-2-carboxylic acid (QC), while five genes (ecm1, 6, 7, 17, 18) are thought to be responsible for the peptide backbone formation and modifications. The aryl carrier protein (ArCP) required for the incorporation of QC into echinomycin is absent from this cluster. Instead, fatty acid synthase acyl carrier protein (FabC) appears to substitute for the echinomycin ArCP, as previously reported for the related triostin A biosynthetic pathway. Subsequently, the echinomycin biosynthetic genes (ecm1-4, 6-8, 11-14, 16-18 and fabC) and sfp, whose translational product is required for phosphopantetheinylation of heterologous acyl carrier proteins in E. coli, were introduced to E. coli to generate a strain capable of echinomycin biosynthesis from simple carbon and nitrogen sources. This is the first report of biosynthesis of biological active form of heterologous NRPs in E. coli. Because of the fast growth rate and ease of maintenance and manipulations of E. coli, this NRP production scheme should serve as foundation toward establishing a general biosynthetic system for economic and flexible production of peptide natural products and their analogs.