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Molecular architectures of benzoic acid-specific type III polyketide synthases

Biphenyl synthase and benzophenone synthase constitute an evolutionarily distinct clade of type III polyketide synthases (PKSs) that use benzoic acid-derived substrates to produce defense metabolites in plants. The use of benzoyl-CoA as an endogenous substrate is unusual for type III PKSs. Moreover,...

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Autores principales: Stewart, Charles, Woods, Kate, Macias, Greg, Allan, Andrew C., Hellens, Roger P., Noel, Joseph P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713876/
https://www.ncbi.nlm.nih.gov/pubmed/29199980
http://dx.doi.org/10.1107/S2059798317016618
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author Stewart, Charles
Woods, Kate
Macias, Greg
Allan, Andrew C.
Hellens, Roger P.
Noel, Joseph P.
author_facet Stewart, Charles
Woods, Kate
Macias, Greg
Allan, Andrew C.
Hellens, Roger P.
Noel, Joseph P.
author_sort Stewart, Charles
collection PubMed
description Biphenyl synthase and benzophenone synthase constitute an evolutionarily distinct clade of type III polyketide synthases (PKSs) that use benzoic acid-derived substrates to produce defense metabolites in plants. The use of benzoyl-CoA as an endogenous substrate is unusual for type III PKSs. Moreover, sequence analyses indicate that the residues responsible for the functional diversification of type III PKSs are mutated in benzoic acid-specific type III PKSs. In order to gain a better understanding of structure–function relationships within the type III PKS family, the crystal structures of biphenyl synthase from Malus × domestica and benzophenone synthase from Hypericum androsaemum were compared with the structure of an archetypal type III PKS: chalcone synthase from Malus × domestica. Both biphenyl synthase and benzophenone synthase contain mutations that reshape their active-site cavities to prevent the binding of 4-coumaroyl-CoA and to favor the binding of small hydrophobic substrates. The active-site cavities of biphenyl synthase and benzophenone synthase also contain a novel pocket associated with their chain-elongation and cyclization reactions. Collectively, these results illuminate structural determinants of benzoic acid-specific type III PKSs and expand the understanding of the evolution of specialized metabolic pathways in plants.
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spelling pubmed-57138762017-12-13 Molecular architectures of benzoic acid-specific type III polyketide synthases Stewart, Charles Woods, Kate Macias, Greg Allan, Andrew C. Hellens, Roger P. Noel, Joseph P. Acta Crystallogr D Struct Biol Research Papers Biphenyl synthase and benzophenone synthase constitute an evolutionarily distinct clade of type III polyketide synthases (PKSs) that use benzoic acid-derived substrates to produce defense metabolites in plants. The use of benzoyl-CoA as an endogenous substrate is unusual for type III PKSs. Moreover, sequence analyses indicate that the residues responsible for the functional diversification of type III PKSs are mutated in benzoic acid-specific type III PKSs. In order to gain a better understanding of structure–function relationships within the type III PKS family, the crystal structures of biphenyl synthase from Malus × domestica and benzophenone synthase from Hypericum androsaemum were compared with the structure of an archetypal type III PKS: chalcone synthase from Malus × domestica. Both biphenyl synthase and benzophenone synthase contain mutations that reshape their active-site cavities to prevent the binding of 4-coumaroyl-CoA and to favor the binding of small hydrophobic substrates. The active-site cavities of biphenyl synthase and benzophenone synthase also contain a novel pocket associated with their chain-elongation and cyclization reactions. Collectively, these results illuminate structural determinants of benzoic acid-specific type III PKSs and expand the understanding of the evolution of specialized metabolic pathways in plants. International Union of Crystallography 2017-11-30 /pmc/articles/PMC5713876/ /pubmed/29199980 http://dx.doi.org/10.1107/S2059798317016618 Text en © Stewart et al. 2017 http://creativecommons.org/licenses/by/2.0/uk/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.http://creativecommons.org/licenses/by/2.0/uk/
spellingShingle Research Papers
Stewart, Charles
Woods, Kate
Macias, Greg
Allan, Andrew C.
Hellens, Roger P.
Noel, Joseph P.
Molecular architectures of benzoic acid-specific type III polyketide synthases
title Molecular architectures of benzoic acid-specific type III polyketide synthases
title_full Molecular architectures of benzoic acid-specific type III polyketide synthases
title_fullStr Molecular architectures of benzoic acid-specific type III polyketide synthases
title_full_unstemmed Molecular architectures of benzoic acid-specific type III polyketide synthases
title_short Molecular architectures of benzoic acid-specific type III polyketide synthases
title_sort molecular architectures of benzoic acid-specific type iii polyketide synthases
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713876/
https://www.ncbi.nlm.nih.gov/pubmed/29199980
http://dx.doi.org/10.1107/S2059798317016618
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