Aspects of the biosynthesis of non-aromatic fungal polyketides by iterative polyketide synthases

Lovastatin biosynthesis in Aspergillus terreus involves two unusual type I multifunctional polyketide syntheses (PKSs). Lovastatin nonaketide synthase (LNKS), the product of the lovB gene, is an iterative PKS that interacts w ith LovC, a putative enoyl reductase, to catalyze the 35 separate reactions in the biosynthesis of dihydromonacolin L, a lovastatin precursor. LNKS al so displays Diels-Alderase activity in vitro. Lovastatin diketide synthase (LDKS) made by lovF, in contrast, acts non-iteratively like the bacterial m odular PKSs to make (2 R)-2-methylbutyric acid. Then, like LNKS, LDKS inter acts closely with another protein, the LovD transesterase enzyme that catal yzes attachment of the 2-methylbutyric acid to monacolin J in the final ste p of the lovastatin pathway. Key features of the genes for these four enzym es and others, plus the regulatory and self-resistance factors involved in lovastatin production, are also described.