SAXS reveals highly flexible interdomain linkers of tandem acyl carrier protein-thioesterase domains from a fungal nonreducing polyketide synthase

FEBS Lett. 2021 Jan;595(1):133-144. doi: 10.1002/1873-3468.13954. Epub 2020 Oct 26.

Abstract

Menisporopsin A is a fungal bioactive macrocyclic polylactone, the biosynthesis of which requires only reducing (R) and nonreducing (NR) polyketide synthases (PKSs) to guide a series of esterification and cyclolactonization reactions. There is no structural information pertaining to these PKSs. Here, we report the solution characterization of singlet and doublet acyl carrier protein (ACP2 and ACP1 -ACP2 )-thioesterase (TE) domains from NR-PKS involved in menisporopsin A biosynthesis. Small-angle X-ray scattering (SAXS) studies in combination with homology modelling reveal that these polypeptides adopt a distinctive beads-on-a-string configuration, characterized by the presence of highly flexible interdomain linkers. These models provide a platform for studying domain organization and interdomain interactions in fungal NR-PKSs, which may be of value in directing the design of functionally optimized polyketide scaffolds.

Keywords: acyl carrier protein; fungal nonreducing polyketide synthase; macrocyclic polylactone; small-angle X-ray scattering; thioesterase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Carrier Protein / chemistry*
  • Circular Dichroism
  • Fungi / enzymology*
  • Macrolides / chemistry
  • Molecular Dynamics Simulation
  • Polyketide Synthases / chemistry*
  • Protein Domains
  • Protein Structure, Secondary
  • Scattering, Small Angle
  • Thiolester Hydrolases / chemistry*
  • X-Ray Diffraction

Substances

  • Acyl Carrier Protein
  • Macrolides
  • menisporopsin A
  • Polyketide Synthases
  • Thiolester Hydrolases