Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:16788062). Acetate is the preferred substrate (PubMed:16788062). Can also utilize propionate with a much lower affinity (By similarity). Provides acetyl-CoA that is utilized mainly for oxidation under ketogenic conditions (By similarity). Involved in thermogenesis under ketogenic conditions, using acetate as a vital fuel when carbohydrate availability is insufficient (By similarity). acetate + ATP + CoA = acetyl-CoA + AMP + diphosphate ATP + CoA + propanoate = AMP + diphosphate + propanoyl-CoA Inhibited by acetylation at Lys-642 and activated by deacetylation mediated by the deacetylase SIRT3. Interacts with SIRT3. Reversibly acetylated on Lys-642 (PubMed:16788062). The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation mediated by the deacetylase SIRT3. Belongs to the ATP-dependent AMP-binding enzyme family. Sequencing errors.