Cargando…

The broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides

Pantothenate synthetase from Escherichia coli (PS(E. coli)) catalyzes the ATP-dependent condensation of (R)-pantoic acid and β-alanine to yield (R)-pantothenic acid (vitamin B(5)), the biosynthetic precursor to coenzyme A. Herein we show that besides the natural amine substrate β-alanine, the enzyme...

Descripción completa

Detalles Bibliográficos
Autores principales: Abidin, Mohammad Z., Saravanan, Thangavelu, Strauss, Erick, Poelarends, Gerrit J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150671/
https://www.ncbi.nlm.nih.gov/pubmed/33913984
http://dx.doi.org/10.1039/d1ob00238d
_version_ 1783698203434024960
author Abidin, Mohammad Z.
Saravanan, Thangavelu
Strauss, Erick
Poelarends, Gerrit J.
author_facet Abidin, Mohammad Z.
Saravanan, Thangavelu
Strauss, Erick
Poelarends, Gerrit J.
author_sort Abidin, Mohammad Z.
collection PubMed
description Pantothenate synthetase from Escherichia coli (PS(E. coli)) catalyzes the ATP-dependent condensation of (R)-pantoic acid and β-alanine to yield (R)-pantothenic acid (vitamin B(5)), the biosynthetic precursor to coenzyme A. Herein we show that besides the natural amine substrate β-alanine, the enzyme accepts a wide range of structurally diverse amines including 3-amino-2-fluoropropionic acid, 4-amino-2-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, and tryptamine for coupling to the native carboxylic acid substrate (R)-pantoic acid to give amide products with up to >99% conversion. The broad amine scope of PS(E. coli) enabled the efficient synthesis of pharmaceutically-relevant vitamin B(5) antimetabolites with excellent isolated yield (up to 89%). This biocatalytic amide synthesis strategy may prove to be useful in the quest for new antimicrobials that target coenzyme A biosynthesis and utilisation.
format Online
Article
Text
id pubmed-8150671
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher The Royal Society of Chemistry
record_format MEDLINE/PubMed
spelling pubmed-81506712021-06-11 The broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides Abidin, Mohammad Z. Saravanan, Thangavelu Strauss, Erick Poelarends, Gerrit J. Org Biomol Chem Chemistry Pantothenate synthetase from Escherichia coli (PS(E. coli)) catalyzes the ATP-dependent condensation of (R)-pantoic acid and β-alanine to yield (R)-pantothenic acid (vitamin B(5)), the biosynthetic precursor to coenzyme A. Herein we show that besides the natural amine substrate β-alanine, the enzyme accepts a wide range of structurally diverse amines including 3-amino-2-fluoropropionic acid, 4-amino-2-hydroxybutyric acid, 4-amino-3-hydroxybutyric acid, and tryptamine for coupling to the native carboxylic acid substrate (R)-pantoic acid to give amide products with up to >99% conversion. The broad amine scope of PS(E. coli) enabled the efficient synthesis of pharmaceutically-relevant vitamin B(5) antimetabolites with excellent isolated yield (up to 89%). This biocatalytic amide synthesis strategy may prove to be useful in the quest for new antimicrobials that target coenzyme A biosynthesis and utilisation. The Royal Society of Chemistry 2021-04-24 /pmc/articles/PMC8150671/ /pubmed/33913984 http://dx.doi.org/10.1039/d1ob00238d Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Abidin, Mohammad Z.
Saravanan, Thangavelu
Strauss, Erick
Poelarends, Gerrit J.
The broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides
title The broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides
title_full The broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides
title_fullStr The broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides
title_full_unstemmed The broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides
title_short The broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides
title_sort broad amine scope of pantothenate synthetase enables the synthesis of pharmaceutically relevant amides
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150671/
https://www.ncbi.nlm.nih.gov/pubmed/33913984
http://dx.doi.org/10.1039/d1ob00238d
work_keys_str_mv AT abidinmohammadz thebroadaminescopeofpantothenatesynthetaseenablesthesynthesisofpharmaceuticallyrelevantamides
AT saravananthangavelu thebroadaminescopeofpantothenatesynthetaseenablesthesynthesisofpharmaceuticallyrelevantamides
AT strausserick thebroadaminescopeofpantothenatesynthetaseenablesthesynthesisofpharmaceuticallyrelevantamides
AT poelarendsgerritj thebroadaminescopeofpantothenatesynthetaseenablesthesynthesisofpharmaceuticallyrelevantamides
AT abidinmohammadz broadaminescopeofpantothenatesynthetaseenablesthesynthesisofpharmaceuticallyrelevantamides
AT saravananthangavelu broadaminescopeofpantothenatesynthetaseenablesthesynthesisofpharmaceuticallyrelevantamides
AT strausserick broadaminescopeofpantothenatesynthetaseenablesthesynthesisofpharmaceuticallyrelevantamides
AT poelarendsgerritj broadaminescopeofpantothenatesynthetaseenablesthesynthesisofpharmaceuticallyrelevantamides