Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis

Polyketides, the ubiquitous products of secondary metabolism in microorgani sms, are made by a process resembling fatty acid biosynthesis that allows t he suppression of reduction or dehydration reactions at specific biosynthet ic steps, giving rise to a wide range of often medically useful products. T he Lovastatin biosynthesis cluster contains two type I polyketide synthase genes. Synthesis of the main nonaketide-derived skeleton was found to requi re the previously known iterative Lovastatin nonaketide synthase (LNKS), pl us at least one additional protein (LovC) that interacts with LNKS and is n ecessary for the correct processing of the growing polyketide chain and pro duction of dihydromonacolin L. The noniterative lovastatin diketide synthas e (LDKS) enzyme specifies formation of 2-methylbutyrate and interacts close ly with an additional transesterase (LovD) responsible for assembling Lovas tatin from this polyketide and monacolin J.