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

Pantothenate synthetase from Escherichia coli (PSE. coli) catalyzes the ATP-dependent condensation of (R)-pantoic acid and β-alanine to yield (R)-pantothenic acid (vitamin B5), 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 PSE. coli enabled the efficient synthesis of pharmaceutically-relevant vitamin B5 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.
Pantothenate synthetase from Escherichia coli (PSE. coli) has a broad substrate scope, accepting diverse amines in the amidation of (R)-pantoate, enabling the facile synthesis of pharmaceutically relevant vitamin B5 antimetabolites.