SAXS reveals highly flexible interdomain linkers of tandem acyl carrier protein–thioesterase domains from a fungal nonreducing polyketide synthase. Issue 1 (26th October 2020)

• Record Type: Journal Article
• Authors: Bunnak, Waraporn; Winter, Ashley J.; Lazarus, Colin M.; Crump, Matthew P.; Race, Paul R.; Wattana‐Amorn, Pakorn
• Is Part Of: FEBS letters. Volume 595:Issue 1(2021)
• Page Start: 133
• Page End: 144
• Publication Date: 2020-10-26
• Subjects: acyl carrier protein -- fungal nonreducing polyketide synthase -- macrocyclic polylactone -- small‐angle X‐ray scattering -- thioesterase; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13954
• Languages: English
• ISSNs: 0014-5793

Abstract

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.