Nonribosomal Peptide Synthesis-Principles and Prospects.
Nonribosomal peptide synthetases (NRPSs) are large multienzyme machineries that assemble numerous peptides with large structural and functional diversity. These peptides include more than 20 marketed drugs, such as antibacterials (penicillin, vancomycin), antitumor compounds (bleomycin), and immunosuppressants (cyclosporine). Over the past few decades biochemical and structural biology studies have gained mechanistic insights into the highly complex assembly line of nonribosomal peptides. This Review provides state-of-the-art knowledge on the underlying mechanisms of NRPSs and the variety of their products along with detailed analysis of the challenges for future reprogrammed biosynthesis. Such a reprogramming of NRPSs would immediately spur chances to generate analogues of existing drugs or new compound libraries of otherwise nearly inaccessible compound structures.
Technische Universität Berlin, Institut für Chemie, Strasse des 17. Juni 124, 10623, Berlin, Germany.
Roderich D
RD
Süssmuth
Technische Universität Berlin, Institut für Chemie, Strasse des 17. Juni 124, 10623, Berlin, Germany.
Andi
A
Mainz
D046908:Peptide Biosynthesis, Nucleic Acid-Independent; D010453:Peptide Synthases / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*
D010455:Peptides; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase
antibiotics; biosynthesis; drug design; enzymes; nonribosomal peptides