ABSTRACT
In biological systems, two different strategies are known for the biosynthesis of peptides: the complex ribosomal machinery and the RNA-independent multienzyme systems called nonribosomal peptide synthetases (NRPSs). The majority of cellular peptides and all proteins are of ribosomal origin. However, many bacteria and fungi nonribosomally produce numerous low-molecular-weight peptides, depsipeptides, peptidolactones, and lipopeptides with linear, branched, or cyclic structures as secondary metabolites. Among these substances are many veterinary agents, agrochemicals, and some of the most important therapeutic natural products in use today, including antiviral and antitumor agents as well as immunosuppressants [1]. The enormous structural diversity and complexity of these biomolecules is impressive. Although the actual biological roles of each of these metabolites in the producing organisms are still unclear, it was speculated rather early that the mechanism of synthesis must differ from that of protein synthesis because the vast majority of microbial peptides often contain unusual amino acids that are not found in proteins. Many of the nonproteinogenic amino acids have unique structures with respect to their carbon skeletons, presence of double bonds, unusual functional groups, or D-configuration at the -carbon atom. The amino acid constituents can also undergo extensive modifications, including N-methylation, acylation, glycosylation, and covalent linkage to other functional groups. They can also introduce structural diversity into nonribosomal peptides and N-methylpeptides [2].
