Abstract
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.
Original language | English |
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Journal | FEBS Letters |
Early online date | 12 Oct 2020 |
DOIs | |
Publication status | Published - 11 Jan 2021 |
Research Groups and Themes
- Bristol BioDesign Institute
- BrisSynBio
Keywords
- acyl carrier protein
- thioesterase
- synthetic biology
- small angle X-ray scattering
- fungal non-reducing polyketide synthase
- macrocyclic polylactone