A nonribosomal system of peptide biosynthesis

This review covers peptide structures originating from the concerted action of enzyme systems without the direct participation of nucleic acids. Biosynthesis proceeds by formation of linear peptidyl intermediates which may be enzymatically modified as well as transformed into specific cyclic structures. The respective enzyme systems are constructed of biosynthetic modules integrated into multienzyme structures. Genetic and DNA-sequence analysis of biosynthetic gene clusters have revealed extensive similarities between prokaryotic and eukaryotic systems, conserved principles of organisation, and a unique mechanism of transport of intermediates during elongation and modification steps involving 4'-phospho-pantetheine. These similarities permit the identification of peptide synthetases and related aminoacyl-ligases and acyl-ligases from sequence data. Similarities to other biosynthetic systems involved in the assembly of polyketide metabolites are discussed.