Understanding the crucial interactions between Cytochrome P450s and non-ribosomal peptide synthetases during glycopeptide antibiotic biosynthesis. (December 2016)

• Record Type: Journal Article
• Authors: Peschke, Madeleine; Gonsior, Melanie; Süssmuth, Roderich D; Cryle, Max J
• Is Part Of: Current opinion in structural biology. Volume 41(2016)
• Page Start: 46
• Page End: 53
• Publication Date: 2016-12
• Subjects: Molecular biology -- Periodicals; 570
• DOI: 10.1016/j.sbi.2016.05.018
• Languages: English
• ISSNs: 0959-440X

Abstract

Graphical abstract: Highlights: Cytochrome P450s are essential for glycopeptide antibiotic (GPA) biosynthesis. Recruitment of these P450s to non-ribosomal peptide synthetases (NRPSs) is crucial. P450s performing amino acid hydroxylation are recruited via carrier protein domains. P450s involved in GPA peptide cyclization are recruited by the X-domain. Recent studies have structurally characterized both types of P450/NRPS complex. Abstract : 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.