Understanding the crucial interactions between Cytochrome P450s and non-ribosomal peptide synthetases during glycopeptide antibiotic biosynthesis.
The importance of Cytochrome P450-catalyzed modifications of natural products produced by non-ribosomal peptide synthetase machineries is most apparent during glycopeptide antibiotic biosynthesis: specifically, the formation of essential amino acid side chains crosslinks in the peptide backbone of these clinically relevant antibiotics. These cyclization reactions take place whilst the peptide substrate remains bound to the non-ribosomal peptide synthetase in a process mediated by a conserved domain of previously unknown function-the X-domain. This review addresses recent advances in understanding P450 recruitment to non-ribosomal peptide synthetase-bound substrates and highlights the importance of both carrier proteins and the X-domain in different P450-catalyzed reactions.
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.
Madeleine
M
Peschke
Institut für Chemie, Technische Universität Berlin, 10623 Berlin, Germany.
Melanie
M
Gonsior
Institut für Chemie, Technische Universität Berlin, 10623 Berlin, Germany. Electronic address: roderich.suessmuth@tu-berlin.de.
Roderich D
RD
Süssmuth
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany; EMBL Australia, Monash University, Clayton, Victoria 3800, Australia; The Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia. Electronic address: max.cryle@monash.edu.
Max J
MJ
Cryle
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D006020:Glycopeptides / Q000096:biosynthesis*; D006801:Humans; D010453:Peptide Synthases / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D003577:Cytochrome P-450 Enzyme System; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase