Nonribosomal biosynthesis of microbial chromopeptides.

Nonribosomal chromopeptides and mixed chromopeptide-polyketides contain aromatic or heteroaromatic side groups which are important recognition elements for interaction with cellular targets such as DNA and proteins, resulting in the biological activities of these natural products. In the chromopeptide lactones and arylpeptide-siderophores from bacteria, the chromophore moiety--an aryl carboxylate amidated to the peptide chain--constitutes the formal amino terminus and is the starter residue of peptide assembly. Common to many arylpeptide systems is the activation by stand-alone adenylation domains and loading of the starter to discrete aryl carrier proteins (ArCPs) or ArCP domains which interact with the modules of the respective nonribosomal peptide synthetase (NRPS), assembling the next residues of the chain. Chain modification is another mechanism of nonribosomal chromopeptide synthesis where heteroaromatic rings such as thiazoles and oxazoles in peptides and polyketides are generated by heterocylizations of acyl- or peptidyl-cysteinyl or -serinyl/threonyl intermediates in each elongation step. In this review the basic mechanisms of chromophore acquisition in nonribosomal chromopeptide synthesis and mixed peptide/polyketide synthesis are illustrated by comparing the biosynthesis systems of various chromopeptides and chromopeptidic polyketide compounds.