In vitro kinetic study of the squalestatin tetraketide synthase dehydratase reveals the stereochemical course of a fungal highly reducing polyketide synthase

Emma Liddle, Alan Scott, Li Chen Han, David Ivison, Thomas J. Simpson, Christine L. Willis, Russell J. Cox*

*Corresponding author for this work

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

9 Citations (Scopus)
304 Downloads (Pure)

Abstract

Six potential diketide substrates for the squalestatin tetraketide synthase (SQTKS) dehydratase (DH) domain were synthesised as N-acetyl cysteamine thiolesters (SNAC) and tested in kinetic assays as substrates with an isolated DH domain. 3R-3-hydroxybutyryl SNAC 3R-16 was turned over by the enzyme, but its enantiomer was not. Of the four 2-methyl substrates only 2R,3R-2-methyl-3-hydroxybutyryl SNAC 2R,3R-8 was a substrate. Combined with stereochemical information from the isolated SQTKS enoyl reductase (ER) domain, our results provide a near complete stereochemical description of the first cycle of beta-modification reactions of a fungal highly reducing polyketide synthase (HR-PKS). The results emphasise the close relationship between fungal HR-PKS and vertebrate fatty acid synthases (vFAS).

Original languageEnglish
Pages (from-to)1727-1730
Number of pages4
JournalChemical Communications
Volume53
Issue number10
Early online date13 Jan 2017
DOIs
Publication statusPublished - 4 Feb 2017

Structured keywords

  • Bristol BioDesign Institute
  • BrisSynBio

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