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 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. Pantothenate synthetase from Escherichia coli (PS E. 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.