Menisporopsin A is a fungal bioactive macrocyclic polylactone requiring only reducing (R) and non-reducing (NR) polyketide synthases (PKSs) to guide a series of esterification and cyclolactonization reactions with 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-aString 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 optimised polyketide scaffolds.
- Bristol BioDesign Institute
- macrocyclic polylactone
- acyl carrier protein
- fungal non-reducing polyketide synthase
- small angle X-ray scattering