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

6 Citations (Scopus)

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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	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

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10.1002/1873-3468.13954

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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

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

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

year = "2021",

month = jan,

day = "11",

doi = "10.1002/1873-3468.13954",

language = "English",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Wiley",

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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 - 2021/1/11

Y1 - 2021/1/11

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 - acyl carrier protein

KW - thioesterase

KW - synthetic biology

KW - small angle X-ray scattering

KW - fungal non-reducing polyketide synthase

KW - macrocyclic polylactone

U2 - 10.1002/1873-3468.13954

DO - 10.1002/1873-3468.13954

M3 - Article (Academic Journal)

C2 - 33043457

SN - 0014-5793

JO - FEBS Letters

JF - FEBS Letters

ER -

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

Abstract

Research Groups and Themes

Keywords

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