Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:11150295, PubMed:16790548). Acetate is the preferred substrate but can also utilize propionate with a much lower affinity (PubMed:11150295). acetate + ATP + CoA = acetyl-CoA + AMP + diphosphate ATP + CoA + propanoate = AMP + diphosphate + propanoyl-CoA Inhibited by acetylation at Lys-661 and activated by deacetylation mediated by the deacetylases SIRT1 and SIRT3. Monomer. Reversibly acetylated at Lys-661 (PubMed:16790548). The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation mediated by the deacetylases SIRT1 and SIRT3. Belongs to the ATP-dependent AMP-binding enzyme family.