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

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

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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 and genomic analysis to feature a bis-thioether macrocyclic ring and a β-enamino acid residue. Biosynthetic investigation demonstrated that its pathway relies on four dedicated proteins: phosphotransferase KinD, Lyase KinC, kinase homolog KinH and flavoprotein KinI, which share low homologues to enzymes known in other RiPP biosynthesis. During the posttranslational modifications, KinCD is responsible for the formation of the characteristic dehydroamino acid residues including the β-enamino acid residue, followed by oxidative decarboxylation on the C-terminal Cys and subsequent cyclization to provide the bis-thioether ring moiety mediated by coordinated action of KinH and KinI. Finally, conserved genomic investigation allows further identification of two kintamdin-like peptides among the kin-like BGCs, suggesting the occurrence of RiPPs from actinobacteria.

Original languageEnglish
Article number5044
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - Dec 2022

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