Molecular genetics of lovastatin and compactin biosynthesis

Lovastatin and the closely related compactin (Fig. 1) are examples of the thousands of known microbial polyketide metabolites, so named because of a characteristic feature of their biosynthesis, the involvement of intermediates containing repeated β-carbonyl motifs [1,2]. These two fungal metabolites were discovered in the late 1970s, and they or drugs derived from them are taken daily by millions of people worldwide to inhibit cholesterol biosynthesis and thereby lessen the untoward effects of an overabundance of serum cholesterol on the cardiovascular system. Their importance in human medicine has resulted in considerable knowledge about their pharmacology and medicinal chemistry [3]. This has in turn led to the development of methods for the large-scale production of lovastatin and compactin and, consequently, an interest in their biosynthesis [4]. This topic is reviewed in this chapter with a focus on the molecular genetics and biochemistry of lovastatin and compactin biosynthesis.