Lovastatin is a cholesterol-lowering drug produced by the filamentous fungus Aspergillus terreus, and is chemically transformed to simvastatin (ZocorŠ), a drug with worldwide sales of $5.3 billion in 2005.  Details of the formation of this metabolite by iterative type 1 polyketide synthases (PKS) will be described. Interestingly, lovastatin nonaketide synthase (lovB) catalyses intramolecular Diels Alder closure of an acyclic triene to a bicyclic system during construction of the main nonaketide skeleton. Studies have been directed at analysis of precursor processing using heterologously-expressed LNKS and its accessory enzyme, lovC protein. In addition, examination of post–PKS transformations by knockout mutants lacking functional lovC protein and lovA protein (a putative P450 enzyme) will be described (3).