Structure-Function Analysis of the Extended Conformation of a Polyketide Synthase Module

J Am Chem Soc. 2018 May 30;140(21):6518-6521. doi: 10.1021/jacs.8b02100. Epub 2018 May 18.


Catalytic modules of assembly-line polyketide synthases (PKSs) have previously been observed in two very different conformations-an "extended" architecture and an "arch-shaped" architecture-although the catalytic relevance of neither has been directly established. By the use of a fully human naïve antigen-binding fragment (Fab) library, a high-affinity antibody was identified that bound to the extended conformation of a PKS module, as verified by X-ray crystallography and tandem size-exclusion chromatography-small-angle X-ray scattering (SEC-SAXS). Kinetic analysis proved that this antibody-stabilized module conformation was fully competent for catalysis of intermodular polyketide chain translocation as well as intramodular polyketide chain elongation and functional group modification of a growing polyketide chain. Thus, the extended conformation of a PKS module is fully competent for all of its essential catalytic functions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biocatalysis
  • Crystallography, X-Ray
  • Humans
  • Kinetics
  • Models, Molecular
  • Polyketide Synthases / chemistry*
  • Polyketide Synthases / metabolism
  • Protein Conformation
  • Scattering, Small Angle
  • X-Ray Diffraction


  • Polyketide Synthases