Discovery and Characterization of a Class IV Lanthipeptide with a Nonoverlapping Ring Pattern

Hengqian Ren, Chengyou Shi, Ian R. Bothwell, Wilfred A. Van Der Donk, Wilfred A. Van Der Donk, Wilfred A. Van Der Donk, Huimin Zhao, Huimin Zhao, Huimin Zhao, Huimin Zhao, Huimin Zhao

Research output: Contribution to journalArticle

Abstract

Lanthipeptides constitute a major family of ribosomally synthesized and post-translationally modified peptides (RiPPs). They are classified into four subfamilies, based on the characteristics of their lanthipeptide synthetases. While over a hundred lanthipeptides have been discovered to date, very few of them are class IV lanthipeptides and the latter are all structurally similar. Here, we identified an uncharacterized group of class IV lanthipeptides using bioinformatics analysis. One representative pathway from Streptomyces sp. NRRL S-1022 was expressed in Escherichia coli, which generated a lanthipeptide with two nonoverlapping rings that have not been reported for known class IV lanthipeptides. Further investigation into the biosynthetic mechanism revealed that multiple modification pathways are in operation in which dehydration and cyclization occur in parallel. While peptidases for maturation of class IV lanthipeptides have been elusive, two aminopeptidases encoded in the genome of Streptomyces sp. NRRL S-1022 were shown to process the modified peptide by the dual endopeptidase/aminopeptidase activity. This work opens doors to discover more class IV lanthipeptides with interesting structural features and biological activities.

Original languageEnglish (US)
Pages (from-to)1642-1649
Number of pages8
JournalACS chemical biology
Volume15
Issue number6
DOIs
StatePublished - Jun 19 2020

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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    Ren, H., Shi, C., Bothwell, I. R., Van Der Donk, W. A., Van Der Donk, W. A., Van Der Donk, W. A., Zhao, H., Zhao, H., Zhao, H., Zhao, H., & Zhao, H. (2020). Discovery and Characterization of a Class IV Lanthipeptide with a Nonoverlapping Ring Pattern. ACS chemical biology, 15(6), 1642-1649. https://doi.org/10.1021/acschembio.0c00267