Comparative Analysis of Lovastatin(an anti cholesterol drug) Genes, LovE and LovF in Soil and Endophytic Fungi

Lovastatin is a competitive inhibitor of the enzyme hydroxymethylglutaryl coenzyme A (HMGCoA) reductase in cholesterol biosynthetic pathway and hence used in the treatment of hyperlipidemia. Our preliminary results revealed that several strains of A. terreus of soil origin produce copious amount of lovastatin than their counterpart which are endophytic in origin. Bioinformatic analysis of whole genome sequence of A .terreus (AH007774.1), a soil isolate revealed the presence of lovastatin gene cluster (AF141924.1& AF141925.1), whereas, endophytic fungi including a strain of Aspergillus terreus showed no homology with the lovastatin gene cluster. The lovastatin gene cluster includes 18 genes that are involved in lovastatin biosynthetic pathway and, of which LovE and LovF encode for transcriptional regulatory factor and diketide synthase (DKS), respectively.  Molecular studies were performed to analyze the expression of lovastatin biosynthetic genes LovE (regulatory gene) and LovF (transcriptional regulatory factor) in soil and endophytic fungi. The target PCR amplification of LovE (1512bp) and LovF (749bp) was successful in strains of Aspergillus terreus (KM017693), soil in origin, whereas the same was not achieved in endophytic fungi. This is the first report on comparative analysis of complementary DNA sequence of soil isolates and endophytic fungi, which validate and confirm the inability of lovastatin production by endophytic fungi. The possible reason for the same will be discussed.