Biosynthesis of Natural Products on Modular Peptide Synthetases

Microbial nonribosomally processed peptides represent a large class of natural products including numerous important pharmaceutical agents, as well as other representatives that play a prevalent role in pathogenicity of certain microorganisms [M. A. Marahiel, T. Stachelhaus, and H. D. Mootz (1997). Chem. Rev. 97, 2651–2673]. Although diverse in structure, nonribosomally synthesized peptides have a common mode of biosynthesis. They are assembled on very large protein templates called peptide synthetases that exhibit a modular organization, allowing polymerization of monomers in an assembly-line-like mechanism.