Lovastatin is a cholesterol-lowering agent produced by the filamentous fungus, Aspergillus terreus, and is a precursor for chemical synthesis of simvastatin (ZocorŠ), a drug that sold over $4.3 billion in 2005. Its biosynthesis proceeds via formation of dihydromonacolin L by a type I iterative polyketide synthase (PKS) known as lovB with cooperation of an enoyl reductase (lovC). An enzyme-catalyzed formal Diels-Alder reaction is implicated at the hexaketide stage. Post-PKS transformations, including P450 oxidation by lovA, introduce the remaining functionality to convert the PKS product to lovastatin. Recent mechanistic studies to elucidate the biosynthesis using enzymes expressed in heterologous hosts will be described. The work includes collaborative efforts and experiments done by the groups of Yi Tang (University of California at Los Angeles), Shiou-Chuan (Sheryl) Tsai (University of California at Irvine) and Dae-Kyun Ro (University of Calgary).