Hydroxymethylglutaryl-CoA synthase; part of the first module of ergosterol biosynthesis pathway that includes the early steps of the pathway, conserved across all eukaryotes, and which results in the formation of mevalonate from acetyl-coenzyme A (acetyl-CoA) (PubMed:23138457). This module also plays a key role in the biosynthesis of triterpenes such as ganoderic acids (GA), a group of highly oxygenated lanostane-type triterpenoids which are well recognized as a main group of unique bioactive compounds in the medicinal mushroom Ganoderma lucidum (PubMed:23138457) (Probable). In this module, the acetyl-CoA acetyltransferase catalyzes the formation of acetoacetyl-CoA (By similarity). The hydroxymethylglutaryl-CoA synthase HMGS then condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA (PubMed:23138457). The rate-limiting step of the early module is the reduction to mevalonate by the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (PubMed:18460810). acetoacetyl-CoA + acetyl-CoA + H2O = (3S)-hydroxy-3-methylglutaryl-CoA + CoA + H(+) Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3. Expression is up-regulated by salicylic acid, abscisic acid and methyl jasmonate. Belongs to the thiolase-like superfamily. HMG-CoA synthase family.