Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis

Katherine Williams, Agnieszka J Szwalbe, Nicholas P Mulholland, Jason L Vincent, Andy Bailey, Christine L Willis, Thomas J Simpson, Russell J Cox

Research output: Contribution to journalArticle (Academic Journal)peer-review

29 Citations (Scopus)
597 Downloads (Pure)

Abstract

Fungal maleidrides are an important family of bioactive secondary metabolites that consist of 7, 8, or 9-membered carbocycles with one or two fused maleic anhydride moieties. The biosynthesis of byssochlamic acid (a nonadride) and agnestadride A (a heptadride) was investigated through gene disruption and heterologous expression experiments. The results reveal that the precursors for cyclization are formed by an iterative highly reducing fungal polyketide synthase supported by a hydrolase, together with two citrate-processing enzymes. The enigmatic ring formation is catalyzed by two proteins with homology to ketosteroid isomerases, and assisted by two proteins with homology to phosphatidylethanolamine-binding proteins.

Original languageEnglish
Pages (from-to)6784-6788
Number of pages5
JournalAngewandte Chemie - International Edition
Volume55
Issue number23
Early online date21 Apr 2016
DOIs
Publication statusPublished - 1 Jun 2016

Keywords

  • biosynthesis
  • cyclization
  • enzymes
  • maleidride
  • polyketides

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