AcsD catalyzes enantioselective citrate desymmetrization in siderophore biosynthesis

Stefan Schmelz, Nadia Kadi, Stephen McMahon, Lijiang Song, Daniel Oves-Costales, Muse Oke, Huanting Liu, Kenneth Alan Johnson, Lester Carter, Catherine Helen Botting, Malcolm F White, Gregory L. Challis, Jim Naismith

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

Abstract

Bacterial pathogens need to scavenge iron from their host for growth and proliferation during infection. They have evolved several strategies to do this, one being the biosynthesis and excretion of small, high-affinity iron chelators known as siderophores. The biosynthesis of siderophores is an important area of study, not only for potential therapeutic intervention but also to illuminate new enzyme chemistries. Two general pathways for siderophore biosynthesis exist: the well-characterized nonribosomal peptide synthetase (NRPS)-dependent pathway and the NRPS-independent siderophore (NIS) pathway, which relies on a different family of sparsely investigated synthetases. Here we report structural and biochemical studies of AcsD from Pectobacterium (formerly Erwinia) chrysanthemi, an NIS synthetase involved in achromobactin biosynthesis. The structures of ATP and citrate complexes provide a mechanistic rationale for stereospecific formation of an enzyme-bound (3R)-citryladenylate, which reacts with L-serine to form a likely achromobactin precursor. AcsD is a unique acyladenylate-forming enzyme with a new fold and chemical catalysis strategy.
Original languageEnglish
Pages (from-to)174-182
Number of pages9
JournalNature Chemical Biology
Volume5
Issue number3
Early online date1 Feb 2009
DOIs
Publication statusPublished - Mar 2009

Keywords

  • NONRIBOSOMAL PEPTIDE SYNTHETASES
  • CRYSTAL-STRUCTURE
  • BACILLUS-ANTHRACIS
  • PETROBACTIN BIOSYNTHESIS
  • ERWINIA-CHRYSANTHEMI
  • STRUCTURAL BASIS
  • PROTEIN-KINASE
  • ACTIVE-SITE
  • COENZYME-A
  • MODEL

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  • BBSRC BBS/B/14426: SPORT

    Naismith, J.

    BBSRC

    18/10/0430/04/12

    Project: Standard

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