Structure and substrate recognition of the Bottromycin maturation enzyme BotP

Greg Mann, Liujie Huo, Sebastian Adam, Brunello Nardone, Jeremie Vendome, Nicholas James Westwood, Rolf Müller, Jesko Koehnke

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)
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Abstract

The bottromycins are a family of highly modified peptide natural products displaying potent antimicrobial activity against Gram-positive bacteria including methicillin-resistant Staphyloccoccus aureus. Bottromycins have recently been shown to be ribosomally synthesized and post-translationally modified peptides (RiPPs). Unique amongst RiPPs the precursor peptide BotA contains a C-terminal "follower" sequence, rather than the canonical N- terminal "leader" sequence. We report the structural and biochemical characterization of BotP, a leucyl-aminopeptidase like enzyme from the bottromycin pathway. We demonstrate that BotP is responsible for the removal of the N-terminal methionine from the precursor peptide. Determining the crystal structures of apo BotP and of BotP in complex with Mn2+ allowed us to model a BotP/substrate complex and to rationalize substrate recognition. Our data represent the first step towards targeted compound modification to unlock the full antibiotic potential of bottromycin.
Original languageEnglish
Pages (from-to)2286-2292
Number of pages7
JournalChemBioChem
Volume17
Issue number23
Early online date21 Sept 2016
DOIs
Publication statusPublished - 2 Dec 2016

Keywords

  • Bottromycin
  • Leucyl-amino peptidase
  • RiPPs
  • BotP
  • Biosynthesis

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