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Working outside the protein‐synthesis rules: insights into non‐ribosomal peptide synthesis
Author(s) -
Marahiel Mohamed A.
Publication year - 2009
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1183
Subject(s) - ribosome , peptide biosynthesis , peptide , ribosomal rna , amino acid , biochemistry , peptide synthesis , nucleic acid , biology , chemistry , ribosomal protein , functional diversity , combinatorial chemistry , computational biology , stereochemistry , rna , gene , ecology
Non‐ribosomally synthesized microbial peptides show remarkable structural diversity and constitute a widespread class of the most potent antibiotics and other important pharmaceuticals that range from penicillin to the immunosuppressant cyclosporine. They are assembled independent of the ribosome in a nucleic acids‐independent way by a group of multimodular megaenzymes called non‐ribosomal peptide synthetases. These biosynthetic machineries rely not only on the 20 canonical amino acids, but also use several different building blocks, including D ‐configured‐ and β‐amino acids, methylated, glycosylated and phosphorylated residues, heterocyclic elements and even fatty acid building blocks. This structural diversity leads to a high density of functional groups, which are often essential for the bioactivity. Recent biochemical and structural studies on several non‐ribosomal peptide synthetase assembly lines have substantially contributed to the understanding of the molecular mechanisms and dynamics of individual catalytic domains underlying substrate recognition and substrate shuffling among the different active sites as well as peptide bond formation and the regio‐ and stereoselective product release. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.