1,3-Diaminopropane and Spermidine Upregulate Lovastatin Production and Expression of Lovastatin Biosynthetic Genes in Aspergillus terreus via LaeA Regulation

Abstract

The filamentous fungus Aspergillus terreus is the main industrial producer of lovastatin, a cholesterol-lowering drug that is also used as a semiproduct for simvastatin production. The exogenous addition of such polyamines as 1,3-diaminopropane or spermidine during the fermentation of wild-type A. terreus ATCC 20542 and overproducing A. terreus 43-16 strains results in a 20−45% increase in lovastatin production. In the case of strain 43-16, the maximum production level (10 g/L) was observed three days earlier than in the control variant. During this fermentation period, the expression level of genes belonging to the lovastatin biosynthetic cluster and the laeA gene (a global regulator of a fungal secondary metabolism) are increased, but the expression patterns for genes of the polyamine metabolic pathway were similar for both strains.