Investigations into PoyH, a promiscuous protease from polytheonamide biosynthesis

Maximilian J. Helf, Michael F. Freeman, Jörn Piel

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Polytheonamides are the most extensively modified ribosomally synthesized and post-translationally modified peptide natural products (RiPPs) currently known. In RiPP biosynthesis, the processed peptide is usually released from a larger precursor by proteolytic cleavage to generate the bioactive terminal product of the pathway. For polytheonamides, which are members of a new RiPP family termed proteusins, we have recently shown that such cleavage is catalyzed by the cysteine protease PoyH acting on the precursor PoyA, both encoded in the polytheonamide biosynthetic gene cluster. We now report activity for PoyH under a variety of reaction conditions for different maturation states of PoyA and demonstrate a potential use of PoyH as a promiscuous protease to liberate and characterize RiPPs from other pathways. As a proof of concept, the identified recognition motif was introduced into precursors of the thiopeptide thiocillin and the lanthipeptide lichenicidin VK1, allowing for their site-specific cleavage with PoyH. Additionally, we show that PoyH cleavage is inhibited by PoyG, a previously uncharacterized chagasin-like protease inhibitor encoded in the polytheonamide gene cluster.

Original languageEnglish (US)
Pages (from-to)551-563
Number of pages13
JournalJournal of Industrial Microbiology and Biotechnology
Volume46
Issue number3-4
DOIs
StatePublished - Mar 29 2019

Keywords

  • Cysteine protease
  • Polytheonamide
  • Post-translational modification
  • RiPP
  • Ribosomal peptide

PubMed: MeSH publication types

  • Journal Article

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