LAUSR

CoA ligases are enzymes catalyzing the ATP‐dependent addition of coenzyme A to carboxylic acids in two steps through an adenylate intermediate. This intermediate can be diverted by a nucleophilic non enzymatic addition of amine to get the corresponding amide for synthetic purposes. To this end, we selected thermophilic CoA ligases to study the conversion of various carboxylic acids into their amide counterparts. To limit the use of ATP, we implemented an ATP regeneration system combining polyphosphate kinase 2 (PPK2 Class III) and inorganic pyrophosphatase. Suitability of this system was illustrated by the lab‐scale chemoenzymatic synthesis of N‐methylbutyrylamide in 77 % yield using low enzyme loading and 5 % molar ATP.