Deuterium Labeled Peptides Give Insights into the Directionality of Class III Lantibiotic Synthetase LabKC
journal contributionposted on 2016-02-20, 19:03 authored by Bartlomiej Krawczyk, Paul Ensle, Wolfgang M. Müller, Roderich D. Süssmuth
The biosynthesis of a considerable number of ribosomally synthesized peptide antibiotics involves the modification of Ser and Thr residues of a precursor peptide. This post-translational processing is performed by one or multiple modifying enzymes encoded in the biosynthetic gene cluster. We present a deuterium-label based enzyme assay, utilizing a series of peptide substrates with α-deuterated Ser, for the determination of the dehydration order during the biosynthesis of class III lantibiotic labyrinthopeptin A2. Remarkably, the data show that, in contrast to other modifying enzymes of class I and II lantibiotics, LabKC has a C- to N-terminal processing mode. This surprising finding, which we consider relevant for the biosyntheses of other class III lantibiotics, underlines significant differences of this class of modifying enzymes compared to other investigated systems.
peptide substratesbiosynthetic gene clusterclass III lantibioticsDeuterium Labeled PeptidesII lantibioticspeptide antibioticsThr residuesenzyme assaydehydration orderdata showSerprecursor peptideclass III lantibiotic labyrinthopeptinClass III Lantibiotic Synthetase LabKCThe biosynthesis2. Remarkably