Characterization of a unique interrupted adenylation domain that can catalyze three reactions

Taylor A. Lundy, Shogo Mori, Nishad Thamban Chandrika, Sylvie Garneau-Tsodikova

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Interrupted adenylation (A) domains contain auxiliary domains within their structure and are a subject of growing interest in the field of nonribosomal peptide biosynthesis. They have been shown to possess intriguing functions and structure as well as promising engineering potential. Here, we present the characterization of an unprecedented type of interrupted A domain from the columbamides biosynthetic pathway, ColG(AMsMbA). This interrupted A domain contains two back-to-back methylation (M) domains within the same interruption site in the A domain, whereas previously, naturally occurring reported and characterized interrupted A domains harbored only one M domain. By a series of radiometric and mass spectrometry assays, we show that the first and second M domains site specifically methylate the side-chain oxygen and backbone nitrogen of l-Ser after the substrate is transferred onto a carrier thiolation domain, ColG(T). This is the first reported characterization of a dimethylating back-to-back interrupted A domain. The insights gained by this work lay the foundation for future combinatorial biosynthesis of site specifically methylated nonribosomal peptides.

Original languageEnglish (US)
Pages (from-to)282-289
Number of pages8
JournalACS Chemical Biology
Issue number1
StatePublished - Jan 17 2020
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine


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