Madeleine Peschke

TL;DR: It is shown that the presentation of peptidyl carrier protein (PCP)-bound substrates for oxidation in GPA biosynthesis requires the presence of the NRPS X-domain to ensure conversion of the precursor peptide into a mature aglycone, and that the carrier protein domain alone is not always sufficient to generate a competent substrate for external cytochrome P450 oxygenases.

TL;DR: 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.

TL;DR: A model for P450 recruitment and peptide modification that involves continuous association/dissociation of the P 450 enzymes with the NRPS, followed by specific recognition of the peptide cyclization state by the P450 (scanning) leads to an induced conformational change that enhances the affinity of the enzyme/substrate complex and initiates catalysis.

TL;DR: The authors obtained a crystal structure of the kistamicin OxyA/X-domain complex and analysed the cyclisation cascade leading to the formation of the A-O-B ring, showing that the kistsicin OxyC enzyme is a promiscuous biocatalyst, able to install multiple crosslinks into peptides containing phenolic amino acids.

TL;DR: It is demonstrated that sequential in vitro P450-catalyzed cyclization of peptide substrates is enabled by the use of an NRPS peptide carrier protein (PCP)-X di-domain as a P450 recruitment platform.