Efficient: In vivo synthesis of lasso peptide pseudomycoidin proceeds in the absence of both the leader and the leader peptidase

Tatyana Zyubko, Marina Serebryakova, Julia Andreeva, Mikhail Metelev, Guy Lippens, Svetlana Dubiley, Konstantin Severinov

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Bacterial lasso peptides are made from linear ribosomally synthesized precursors by specific cleavage at the leader-core junction site of the precursor by a dedicated protease recognizing the leader, followed by cyclisation of the newly formed N-terminus of the core part with a side chain of the internal aspartic or glutamic residue catalyzed by a macrolactam synthetase. The resulting structure has a tail that is threaded and fixed inside the cycle formed. Here, we characterize a new lasso peptide, pseudomycoidin, encoded by Bacillus pseudomycoides DSM 12442. The most surprising and unique feature of pseudomycoidin is that it can be produced in vivo from the ribosomally synthesized core part by a macrolactam synthetase, in the absence of the leader protease. The minimalism of the pseudomycoidin synthesis system makes it a powerful model to generate pseudomycoidin-based lasso-peptide libraries and to study the poorly understood process of lasso formation. We detected two additional pseudomycoidin modifications: phosphorylation of a terminal residue that was previously observed in another lasso peptide, followed by glycosylation, which was not observed heretofore. We speculate that these bulky C-terminal modifications may help maintain the threaded lasso topology of the compound synthesized by the macrolactam synthetase.

Original languageEnglish (US)
Pages (from-to)9699-9707
Number of pages9
JournalChemical Science
Volume10
Issue number42
DOIs
StatePublished - 2019

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

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