SAXS reveals highly flexible interdomain linkers of tandem acyl carrier protein–thioesterase domains from a fungal non‐reducing polyketide synthase

Waraporn Bunnak; Ashley J Winter; Colin M Lazarus; Matthew P Crump; Paul R Race; Pakorn Wattana-Amorn

doi:10.1002/1873-3468.13954

SAXS reveals highly flexible interdomain linkers of tandem acyl carrier protein–thioesterase domains from a fungal non‐reducing polyketide synthase

Waraporn Bunnak, Ashley J Winter, Colin M Lazarus, Matthew P Crump, Paul R Race, Pakorn Wattana-Amorn

Research output: Contribution to journal › Article (Academic Journal) › peer-review

11 Downloads (Pure)

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
Journal	FEBS Letters
Early online date	12 Oct 2020
DOIs	https://doi.org/10.1002/1873-3468.13954
Publication status	E-pub ahead of print - 12 Oct 2020

Structured keywords

Bristol BioDesign Institute
BrisSynBio

Keywords

macrocyclic polylactone
thioesterase
acyl carrier protein
fungal non-reducing polyketide synthase
small angle X-ray scattering

Access to Document

10.1002/1873-3468.13954

Full-text PDF (author’s accepted manuscript)
This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Wiley at https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.13954 . Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 1.11 MB
Supplementary information PDFAccepted author manuscript, 2.65 MB

Cite this

@article{3b5ac0dc2a9b48579155578887ba388f,

title = "SAXS reveals highly flexible interdomain linkers of tandem acyl carrier protein–thioesterase domains from a fungal non‐reducing polyketide synthase",

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.",

keywords = "macrocyclic polylactone, thioesterase, acyl carrier protein, fungal non-reducing polyketide synthase, small angle X-ray scattering",

author = "Waraporn Bunnak and Winter, {Ashley J} and Lazarus, {Colin M} and Crump, {Matthew P} and Race, {Paul R} and Pakorn Wattana-Amorn",

year = "2020",

month = oct,

day = "12",

doi = "10.1002/1873-3468.13954",

language = "English",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Wiley",

}

SAXS reveals highly flexible interdomain linkers of tandem acyl carrier protein–thioesterase domains from a fungal non‐reducing polyketide synthase. / Bunnak, Waraporn; Winter, Ashley J; Lazarus, Colin M; Crump, Matthew P ; Race, Paul R; Wattana-Amorn, Pakorn.

In: FEBS Letters, 12.10.2020.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - SAXS reveals highly flexible interdomain linkers of tandem acyl carrier protein–thioesterase domains from a fungal non‐reducing polyketide synthase

AU - Bunnak, Waraporn

AU - Winter, Ashley J

AU - Lazarus, Colin M

AU - Crump, Matthew P

AU - Race, Paul R

AU - Wattana-Amorn, Pakorn

PY - 2020/10/12

Y1 - 2020/10/12

N2 - 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.

AB - 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.

KW - macrocyclic polylactone

KW - thioesterase

KW - acyl carrier protein

KW - fungal non-reducing polyketide synthase

KW - small angle X-ray scattering

U2 - 10.1002/1873-3468.13954

DO - 10.1002/1873-3468.13954

M3 - Article (Academic Journal)

C2 - 33043457

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

ER -

SAXS reveals highly flexible interdomain linkers of tandem acyl carrier protein–thioesterase domains from a fungal non‐reducing polyketide synthase

Abstract

Structured keywords

Keywords

Access to Document

Fingerprint

Cite this