Radical SAM Enzyme QmpB Installs Two 9-Membered Ring Sactionine Macrocycles during Biogenesis of a Ribosomal Peptide Natural Product
Alessio Caruso, Mohammad R. Seyedsayamdost
Abstract
We report the reaction catalyzed by QmpB, a new radical S-adenosylmethionine enzyme encoded by a ribosomal peptide natural product gene cluster in Streptococcus suis. Using isotopic labeling, site-directed mutagenesis, high-resolution mass spectrometry, and multidimensional NMR spectroscopy, we show that QmpB installs two 9-membered ring sactionine bridges, connecting a Cys residue with an upstream Asn via an α-thioether bridge, with the two macrocycles separated by a single residue. QmpB is only the second type II sactionine synthase characterized to date.
Topics & Concepts
ChemistryThioetherResidue (chemistry)Natural productBiogenesisStereochemistryNuclear magnetic resonance spectroscopyPeptideEnzymeMass spectrometryRing (chemistry)Combinatorial chemistryBiochemistryOrganic chemistryGeneChromatographyRNA and protein synthesis mechanismsMetalloenzymes and iron-sulfur proteinsChemical Synthesis and Analysis