Nonribosomal peptide synthetases involved in the production of medically relevant natural products.
Natural products biosynthesized wholly or in part by nonribosomal peptide synthetases (NRPSs) are some of the most important drugs currently used clinically for the treatment of a variety of diseases. Since the initial research into NRPSs in the early 1960s, we have gained considerable insights into the mechanism by which these enzymes assemble these natural products. This review will present a brief history of how the basic mechanistic steps of NRPSs were initially deciphered and how this information has led us to understand how nature modified these systems to generate the enormous structural diversity seen in nonribosomal peptides. This review will also briefly discuss how drug development and discovery are being influenced by what we have learned from nature about nonribosomal peptide biosynthesis.
Felnagle
Elizabeth A
EA
Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Jackson
Emily E
EE
Chan
Yolande A
YA
Podevels
Angela M
AM
Berti
Andrew D
AD
McMahon
Matthew D
MD
Thomas
Michael G
MG
D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D001688:Biological Products / Q000096:biosynthesis*; D001761:Bleomycin / Q000096:biosynthesis; D002207:Capreomycin / Q000096:biosynthesis; D020134:Catalytic Domain; D016572:Cyclosporine / Q000378:metabolism; D006020:Glycopeptides / Q000096:biosynthesis; D046908:Peptide Biosynthesis, Nucleic Acid-Independent; D010453:Peptide Synthases / Q000737:chemistry / Q000502:physiology*; D011810:Quinoxalines / Q000378:metabolism; D047090:beta-Lactams / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001688:Biological Products; D006020:Glycopeptides; D011810:Quinoxalines; D047090:beta-Lactams; D002207:Capreomycin; D001761:Bleomycin; D016572:Cyclosporine; D010453:Peptide Synthases