An Iterative Module in the Azalomycin F Polyketide Synthase Contains a Switchable Enoylreductase Domain

Angew Chem Int Ed Engl. 2017 May 8;56(20):5503-5506. doi: 10.1002/anie.201701220. Epub 2017 Apr 18.

Abstract

Detailed analysis of the modular Type I polyketide synthase (PKS) involved in the biosynthesis of the marginolactone azalomycin F in mangrove Streptomyces sp. 211726 has shown that only nineteen extension modules are required to accomplish twenty cycles of polyketide chain elongation. Analysis of the products of a PKS mutant specifically inactivated in the dehydratase domain of extension-module 1 showed that this module catalyzes two successive elongations with different outcomes. Strikingly, the enoylreductase domain of this module can apparently be "toggled" off and on : it functions in only the second of these two cycles. This novel mechanism expands our understanding of PKS assembly-line catalysis and may explain examples of apparent non-colinearity in other modular PKS systems.

Keywords: antibiotics; biosynthesis; enoylreductases; iteration modules; macrocyclic polyketides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Macrolides / chemistry
  • Macrolides / metabolism*
  • Molecular Conformation
  • Mutation
  • Oxidoreductases / chemistry*
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Polyketide Synthases / chemistry*
  • Polyketide Synthases / genetics
  • Polyketide Synthases / metabolism*

Substances

  • Macrolides
  • azalomycin-F
  • Polyketide Synthases
  • Oxidoreductases