In enzymology, a propionate—CoA ligase (EC 6.2.1.17) is an enzyme that catalyzes the chemical reaction

ATP + propanoate + CoA ${\displaystyle \rightleftharpoons }$ AMP + diphosphate + propanoyl-CoA

The 3 substrates of this enzyme are ATP, propanoate, and CoA, whereas its 3 products are AMP, diphosphate, and propanoyl-CoA.

This enzyme belongs to the family of ligases, specifically those forming carbon-sulfur bonds as acid-thiol ligases. The systematic name of this enzyme class is propanoate:CoA ligase (AMP-forming). This enzyme is also called propionyl-CoA synthetase. This enzyme participates in propanoate metabolism.