A ribosomally synthesised and post-translationally modified peptide containing a β-enamino acid and a macrocyclic motif

• DOI: 10.1038/s41467-022-32774-3
• Publication Date: 2022-08-26T14:03:41Z
• Authors: Shan Wang; Sixing Lin; Qing Fang; Roland Gyampoh; Zhou Lu; Yingli Gao; David J. Clarke; Kewen Wu; Laurent Trembleau; Yi Yu; Kwaku Kyeremeh; Bruce F. Milne; Jioji Tabudravu; Hai Deng
• Keywords: Residue (chemistry); Thioether; Moiety

Abstract Ribosomally synthesized and post-translationally modified peptides (RiPPs) are structurally complex natural products with diverse bioactivities. Here we report discovery of a RiPP, kintamdin, for which the structure is determined through spectroscopy, spectrometry genomic analysis to feature bis -thioether macrocyclic ring β-enamino acid residue. Biosynthetic investigation demonstrated that its pathway relies on four dedicated proteins: phosphotransferase KinD, Lyase KinC, kinase homolog KinH flavoprotein KinI, share low homologues enzymes known in other RiPP biosynthesis. During posttranslational modifications, KinCD responsible formation characteristic dehydroamino residues including residue, followed by oxidative decarboxylation C-terminal Cys subsequent cyclization provide moiety mediated coordinated action KinI. Finally, conserved allows further identification two kintamdin-like among kin -like BGCs, suggesting occurrence RiPPs from actinobacteria.