Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). Functions in the mevalonate (MVA) pathway leading to isopentenyl diphosphate (IPP), a key precursor for the biosynthesis of isoprenoid compounds. acetoacetyl-CoA + acetyl-CoA + H2O = (3S)-hydroxy-3-methylglutaryl-CoA + CoA + H(+) Is sensitive to feedback substrate inhibition by acetoacetyl-CoA. Is inactivated by hymeglusin, which also blocks the growth of E.faecalis, indicating the critical role that the mevalonate pathway plays in isoprenoid biosynthesis. Optimum pH is about 9.8. Optimum temperature is 37 degrees Celsius. Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3. Homodimer. Belongs to the thiolase-like superfamily. HMG-CoA synthase family.